实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (1): 74-84.DOI: 10.12300/j.issn.1674-5817.2023.062
梁天薇, 邓亚胜, 黄慧, 荣娜, 刘鑫, 王玉洁, 林江()()
收稿日期:
2023-05-11
修回日期:
2023-08-04
出版日期:
2024-02-25
发布日期:
2024-03-07
通讯作者:
林 江(1963—),女,博士,教授,博士生导师,全国第七批名老中医药专家学术经验继承工作指导老师,研究方向:方剂组方原理、临床应用及实验研究。E-mail: 1713552545@qq.com。ORCID:0009-0009-6182-2335作者简介:
梁天薇(1997—),女,硕士研究生,研究方向:特色方剂配伍及成药化研究。E-mail:1959494476@qq.com
基金资助:
Tianwei LIANG, Yasheng DENG, Hui HUANG, Na RONG, Xin LIU, Yujie WANG, Jiang LIN()()
Received:
2023-05-11
Revised:
2023-08-04
Published:
2024-02-25
Online:
2024-03-07
Contact:
LIN Jiang (ORCID: 0009-0009-6182-2335), E-mail: 1713552545@qq.com摘要:
目的 对已报道的围绝经期综合征(perimenopausal syndrome,PS)动物模型制备方法进行综合分析,比较模型制备各要素和检测指标的优缺点,为优化相关动物模型并规范其在新药疗效评价中的运用提供有益参考。 方法 采用文献研究方法,以“围绝经期综合征”和“perimenopausal syndrome”等为主题词,在中国知网、万方数据、PubMed等数据库中检索2016年1月—2023年2月发表的与PS动物模型制备相关的文献,按照纳入标准和排除标准筛选出符合PS动物模型制备的实验文献,梳理文献中详细记载的实验动物品系、造模方法、给药时长、阳性药物、检测指标等相关信息。将上述信息统一进行标准化处理后,利用Excel2010表格建立PS动物模型数据库,系统归纳总结模型制备要素和评价指标,并用Excel 2010软件进行统计学处理和分析。 结果 共筛选出247篇文献。制备PS动物模型常选用SD大鼠(164次,65.86%)和Wistar大鼠(35次,14.06%)。造模方法常选择双侧卵巢摘除法(139次,53.87%)和自然老化法(43次,16.80%)。用于建模的大鼠年龄从7周龄~18月龄不等,其中以3月龄大鼠(22次,21.78%)最常用。关于检测指标,大多采用血清生化、阴道脱落细胞涂片、组织形态学、一般情况观察、行为学观察以及脏器组织蛋白免疫印迹等多指标进行综合评价。检验模型是否成功制备常选用西医评价指标,西医常用阴道脱落细胞涂片方法判定动情周期(125次,85.04%),待实验者观察到实验动物动情周期紊乱或不规则即可认为模型制备成功;同时也有部分文献通过检测发现血清雌二醇含量明显降低来判定造模成功(5次,3.04%)。中医证型评价常采用中西医评价指标相结合的方法进行综合评价,实验者通过阴道脱落细胞涂片辅以一般情况观察判断中医证型(3次,2.04%)。 结论 目前已有的PS动物模型制备方法较多,但相关研究在动物种属选择、动物年龄、造模成功标准、中医证型评价等方面仍存在较大差异。
中图分类号:
梁天薇, 邓亚胜, 黄慧, 荣娜, 刘鑫, 王玉洁, 林江. 围绝经期综合征动物模型的制备方法及评价指标分析[J]. 实验动物与比较医学, 2024, 44(1): 74-84.
Tianwei LIANG, Yasheng DENG, Hui HUANG, Na RONG, Xin LIU, Yujie WANG, Jiang LIN. Preparation Methods and Evaluation Criteria Analysis of Animal Models for Perimenopausal Syndrome[J]. Laboratory Animal and Comparative Medicine, 2024, 44(1): 74-84.
动物 Animals | 使用频次/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|
SD大鼠 Sprague-Dawley rats | 164 | 65.86 |
Wistar大鼠 Wistar rats | 35 | 14.06 |
ICR小鼠 ICR mice | 20 | 8.03 |
C57BL/6小鼠 C57BL/6 mice | 9 | 3.62 |
KM小鼠 KM mice | 7 | 2.81 |
C57BL/6N小鼠 C57BL/6N mice | 3 | 1.21 |
C57BL/6J小鼠 C57BL/6J mice | 3 | 1.21 |
BALB/c小鼠 BALB/c mice | 2 | 0.80 |
基因敲除小鼠 Knockout mice | 2 | 0.80 |
ddY小鼠 ddY mice | 1 | 0.40 |
Fischer-344-CDF大鼠 Fischer-344-CDF rats | 1 | 0.40 |
褐家鼠 Rattus norvegicus | 1 | 0.40 |
狨猴 Marmosets | 1 | 0.40 |
表1 围绝经期综合征模型的动物使用情况分布
Table 1 Distribution of animal usage of PS models
动物 Animals | 使用频次/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|
SD大鼠 Sprague-Dawley rats | 164 | 65.86 |
Wistar大鼠 Wistar rats | 35 | 14.06 |
ICR小鼠 ICR mice | 20 | 8.03 |
C57BL/6小鼠 C57BL/6 mice | 9 | 3.62 |
KM小鼠 KM mice | 7 | 2.81 |
C57BL/6N小鼠 C57BL/6N mice | 3 | 1.21 |
C57BL/6J小鼠 C57BL/6J mice | 3 | 1.21 |
BALB/c小鼠 BALB/c mice | 2 | 0.80 |
基因敲除小鼠 Knockout mice | 2 | 0.80 |
ddY小鼠 ddY mice | 1 | 0.40 |
Fischer-344-CDF大鼠 Fischer-344-CDF rats | 1 | 0.40 |
褐家鼠 Rattus norvegicus | 1 | 0.40 |
狨猴 Marmosets | 1 | 0.40 |
造模因素 Modeling factors | 造模方法 Modelling method | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|---|
卵巢去势 Ovariectomy | 双侧卵巢摘除术 | 139 | 54.30 |
一侧完全摘除,另一侧摘除80% | 4 | 1.56 | |
一侧完全摘除,另一侧摘除50% | 2 | 0.78 | |
一侧完全摘除,另一侧摘除20% | 1 | 0.39 | |
自然老化 Natural aging method | 自然老化法 | 43 | 16.80 |
环境化学物质 Environmental chemicals | 注射4-二氧化乙烯基环己烯(VCD) | 11 | 4.30 |
化学药物 Chemical drugs | 超促排卵药物 | 4 | 1.56 |
卵巢注射无水乙醇 | 2 | 0.78 | |
灌服雷公藤多苷片 | 1 | 0.39 | |
复合因素 Compounding factors | 双侧卵巢摘除术联合慢性束缚法 | 1 | 0.39 |
双侧卵巢摘除术联合慢性不可预知刺激 | 10 | 3.91 | |
双侧卵巢摘除术联合电刺激 | 2 | 0.78 | |
双侧卵巢摘除术加高脂饮食 | 1 | 0.39 | |
双侧卵巢摘除术联合CO2刺激 | 1 | 0.39 | |
双侧卵巢摘除术加睡眠剥夺 | 1 | 0.39 | |
注射VCD联合慢性束缚法 | 2 | 0.78 | |
病证结合 Disease-syndrome combination | 自然老化加注射氢化可的松 | 13 | 5.08 |
自然老化联合慢性束缚刺激 | 8 | 3.13 | |
双侧卵巢摘除术加灌服热性中药 | 5 | 1.95 | |
双侧卵巢摘除术联合慢性不可预知刺激 | 5 | 1.95 |
表2 围绝经期综合征动物模型造模方法分布
Table 2 Distribution of modeling methods for perimenopausal syndrome animal models
造模因素 Modeling factors | 造模方法 Modelling method | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|---|
卵巢去势 Ovariectomy | 双侧卵巢摘除术 | 139 | 54.30 |
一侧完全摘除,另一侧摘除80% | 4 | 1.56 | |
一侧完全摘除,另一侧摘除50% | 2 | 0.78 | |
一侧完全摘除,另一侧摘除20% | 1 | 0.39 | |
自然老化 Natural aging method | 自然老化法 | 43 | 16.80 |
环境化学物质 Environmental chemicals | 注射4-二氧化乙烯基环己烯(VCD) | 11 | 4.30 |
化学药物 Chemical drugs | 超促排卵药物 | 4 | 1.56 |
卵巢注射无水乙醇 | 2 | 0.78 | |
灌服雷公藤多苷片 | 1 | 0.39 | |
复合因素 Compounding factors | 双侧卵巢摘除术联合慢性束缚法 | 1 | 0.39 |
双侧卵巢摘除术联合慢性不可预知刺激 | 10 | 3.91 | |
双侧卵巢摘除术联合电刺激 | 2 | 0.78 | |
双侧卵巢摘除术加高脂饮食 | 1 | 0.39 | |
双侧卵巢摘除术联合CO2刺激 | 1 | 0.39 | |
双侧卵巢摘除术加睡眠剥夺 | 1 | 0.39 | |
注射VCD联合慢性束缚法 | 2 | 0.78 | |
病证结合 Disease-syndrome combination | 自然老化加注射氢化可的松 | 13 | 5.08 |
自然老化联合慢性束缚刺激 | 8 | 3.13 | |
双侧卵巢摘除术加灌服热性中药 | 5 | 1.95 | |
双侧卵巢摘除术联合慢性不可预知刺激 | 5 | 1.95 |
动物 Animals | 年龄 Age | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|---|
大鼠 Rat | 6周龄 | 5 | 4.95 |
7周龄 | 4 | 3.96 | |
6~8周龄 | 3 | 2.97 | |
8周龄 | 11 | 10.89 | |
8~10周龄 | 2 | 1.98 | |
10周龄 | 6 | 5.94 | |
11周龄 | 2 | 1.98 | |
12周龄 | 9 | 8.92 | |
2月龄 | 5 | 4.95 | |
2~3月龄 | 2 | 1.98 | |
3月龄 | 22 | 21.78 | |
3~4月龄 | 2 | 1.98 | |
4月龄 | 5 | 4.95 | |
6月龄 | 4 | 3.96 | |
小鼠 Mouse | 7周龄 | 2 | 9.53 |
8周龄 | 7 | 33.33 |
表3 卵巢摘除法建立围绝经期综合征动物模型的动物年龄分布
Table 3 Distribution of animal age in ovariectomy-induced perimenopausal syndrome animal model
动物 Animals | 年龄 Age | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|---|
大鼠 Rat | 6周龄 | 5 | 4.95 |
7周龄 | 4 | 3.96 | |
6~8周龄 | 3 | 2.97 | |
8周龄 | 11 | 10.89 | |
8~10周龄 | 2 | 1.98 | |
10周龄 | 6 | 5.94 | |
11周龄 | 2 | 1.98 | |
12周龄 | 9 | 8.92 | |
2月龄 | 5 | 4.95 | |
2~3月龄 | 2 | 1.98 | |
3月龄 | 22 | 21.78 | |
3~4月龄 | 2 | 1.98 | |
4月龄 | 5 | 4.95 | |
6月龄 | 4 | 3.96 | |
小鼠 Mouse | 7周龄 | 2 | 9.53 |
8周龄 | 7 | 33.33 |
动物 Animals | 月龄 Months of age | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|---|
大鼠 Rat | 10~12 | 4 | 8.00 |
11 | 2 | 4.00 | |
11~12 | 5 | 10.00 | |
12 | 9 | 18.00 | |
11~14 | 3 | 6.00 | |
13 | 6 | 12.00 | |
12~14 | 3 | 6.00 | |
14 | 2 | 4.00 | |
13~15 | 2 | 4.00 | |
11~15 | 2 | 4.00 | |
12~13 | 2 | 4.00 | |
13~16 | 2 | 4.00 | |
16 | 2 | 4.00 | |
小鼠 Mouse | 11 | 4 | 36.36 |
12 | 4 | 36.36 |
表4 自然老化法建立围绝经期综合征动物模型的动物月龄分布
Table 4 Distribution of animal age in perimenopausal syndrome animal model established by natural aging method
动物 Animals | 月龄 Months of age | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|---|
大鼠 Rat | 10~12 | 4 | 8.00 |
11 | 2 | 4.00 | |
11~12 | 5 | 10.00 | |
12 | 9 | 18.00 | |
11~14 | 3 | 6.00 | |
13 | 6 | 12.00 | |
12~14 | 3 | 6.00 | |
14 | 2 | 4.00 | |
13~15 | 2 | 4.00 | |
11~15 | 2 | 4.00 | |
12~13 | 2 | 4.00 | |
13~16 | 2 | 4.00 | |
16 | 2 | 4.00 | |
小鼠 Mouse | 11 | 4 | 36.36 |
12 | 4 | 36.36 |
阳性对照药物 Positive control drugs | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|
戊酸雌二醇 Estradiol valerate tablets | 54 | 31.21 |
雌激素 Estrogen | 30 | 17.92 |
更年安片 Gengnianan tablet | 14 | 8.09 |
替勃龙 Tibolone | 12 | 6.93 |
结合雌激素 Conjugated equine estrogen | 7 | 4.05 |
己烯雌酚 Diethylstilbestrol | 6 | 3.47 |
坤宝丸 Kunbao pill | 6 | 3.47 |
教材方 Teaching materials | 5 | 2.88 |
大豆异黄酮 Soybean isoflavones | 5 | 2.88 |
右归丸 Yougui Pill | 4 | 2.31 |
尼尔雌醇 Nilestriol | 3 | 1.73 |
坤泰胶囊 Kuntai Capsule | 3 | 1.73 |
莉芙敏 Remifemin | 3 | 1.73 |
苯甲酸雌二醇 Estradiol benzoate | 2 | 1.16 |
17α -乙炔雌二醇 17α-Ethinyl oestradiol | 2 | 1.16 |
染料木黄酮 Genistein | 2 | 1.16 |
六味地黄丸 Liuwei Dihuang Pills | 2 | 1.16 |
地西泮 Diazepam | 2 | 1.16 |
静心口服液 Jingxin oral liquid | 1 | 0.58 |
红三叶草提取物 Red clover dry extracts | 1 | 0.58 |
雷洛昔芬 Raloxifen | 1 | 0.58 |
黄芪精口服液 Milkvetch root oral liquids | 1 | 0.58 |
滋肾养阴汤 Zishen yangyin decoction | 1 | 0.58 |
市售蜂蜜 Commercially available honey | 1 | 0.58 |
柴胡疏肝散 Chaihu Shugan Powder | 1 | 0.58 |
左归丸 Zougui Pill | 1 | 0.58 |
更年欣胶囊 Gengnianxin capsule | 1 | 0.58 |
更年乐片 Gengnianle tablet | 1 | 0.58 |
表5 围绝经期综合征动物模型建立时阳性对照药物使用频数分布
Table 5 Frequency distribution of positive control drugs used in the establishment of perimenopausal syndrome animal model
阳性对照药物 Positive control drugs | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|
戊酸雌二醇 Estradiol valerate tablets | 54 | 31.21 |
雌激素 Estrogen | 30 | 17.92 |
更年安片 Gengnianan tablet | 14 | 8.09 |
替勃龙 Tibolone | 12 | 6.93 |
结合雌激素 Conjugated equine estrogen | 7 | 4.05 |
己烯雌酚 Diethylstilbestrol | 6 | 3.47 |
坤宝丸 Kunbao pill | 6 | 3.47 |
教材方 Teaching materials | 5 | 2.88 |
大豆异黄酮 Soybean isoflavones | 5 | 2.88 |
右归丸 Yougui Pill | 4 | 2.31 |
尼尔雌醇 Nilestriol | 3 | 1.73 |
坤泰胶囊 Kuntai Capsule | 3 | 1.73 |
莉芙敏 Remifemin | 3 | 1.73 |
苯甲酸雌二醇 Estradiol benzoate | 2 | 1.16 |
17α -乙炔雌二醇 17α-Ethinyl oestradiol | 2 | 1.16 |
染料木黄酮 Genistein | 2 | 1.16 |
六味地黄丸 Liuwei Dihuang Pills | 2 | 1.16 |
地西泮 Diazepam | 2 | 1.16 |
静心口服液 Jingxin oral liquid | 1 | 0.58 |
红三叶草提取物 Red clover dry extracts | 1 | 0.58 |
雷洛昔芬 Raloxifen | 1 | 0.58 |
黄芪精口服液 Milkvetch root oral liquids | 1 | 0.58 |
滋肾养阴汤 Zishen yangyin decoction | 1 | 0.58 |
市售蜂蜜 Commercially available honey | 1 | 0.58 |
柴胡疏肝散 Chaihu Shugan Powder | 1 | 0.58 |
左归丸 Zougui Pill | 1 | 0.58 |
更年欣胶囊 Gengnianxin capsule | 1 | 0.58 |
更年乐片 Gengnianle tablet | 1 | 0.58 |
高频检测指标 High frequency detection indexes | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|
血清生化指标 Serum biochemical indicators | 190 | 19.09 |
阴道脱落细胞涂片 Shed cell of vaginal smears | 140 | 14.07 |
脏器形态学观察 Morphology observation of organs | 92 | 9.24 |
一般情况(体重、饮水量、外观、活动等) General condition (weight, water intake, appearance, activity, etc.) | 84 | 8.44 |
行为学观察 Behavioral observation | 68 | 6.83 |
脏器免疫组化 Immunohistochemistry | 56 | 5.62 |
脏器组织蛋白质印迹 Western blotting | 54 | 5.42 |
实时定量PCR检测相关mRNA表达 Real-time quantitative PCR of mRNA expression | 54 | 5.42 |
脏器湿重 Organ wet weight | 51 | 5.12 |
脏器指数(系数) Visceral index (factor) | 50 | 5.02 |
脏器组织匀浆生化 Biochemicals of organ tissue homogenates | 42 | 4.22 |
尾部皮肤和肛门温度 Tail skin and rectal temperature | 21 | 2.11 |
CT扫描骨形态计量学参数 Bone histomorphometric parameters by CT scan | 12 | 1.20 |
TUNEL染色检测脏器细胞凋亡 TUNEL staining of organ cell apoptosis | 11 | 1.10 |
免疫荧光法检测相关蛋白分布 Immunofluorescence assay for protein distribution | 9 | 0.90 |
戊巴比妥钠睡眠试验 Pentobarbital sodium sleep test | 7 | 0.70 |
代谢组学 Metabolomics | 6 | 0.60 |
肠道菌群 Intestinal flora | 5 | 0.50 |
X线测骨密度 Bone density measured by X-Ray | 5 | 0.50 |
原位杂交法检测相关mRNA表达 In situ hybridization of mRNA expression | 5 | 0.50 |
表6 围绝经期综合征动物模型建立后的高频检测指标分布
Table 6 Distribution of high frequency detection indexes in perimenopausal syndrome animal models
高频检测指标 High frequency detection indexes | 频数/次 Frequency/time | 百分比/% Percentage/% |
---|---|---|
血清生化指标 Serum biochemical indicators | 190 | 19.09 |
阴道脱落细胞涂片 Shed cell of vaginal smears | 140 | 14.07 |
脏器形态学观察 Morphology observation of organs | 92 | 9.24 |
一般情况(体重、饮水量、外观、活动等) General condition (weight, water intake, appearance, activity, etc.) | 84 | 8.44 |
行为学观察 Behavioral observation | 68 | 6.83 |
脏器免疫组化 Immunohistochemistry | 56 | 5.62 |
脏器组织蛋白质印迹 Western blotting | 54 | 5.42 |
实时定量PCR检测相关mRNA表达 Real-time quantitative PCR of mRNA expression | 54 | 5.42 |
脏器湿重 Organ wet weight | 51 | 5.12 |
脏器指数(系数) Visceral index (factor) | 50 | 5.02 |
脏器组织匀浆生化 Biochemicals of organ tissue homogenates | 42 | 4.22 |
尾部皮肤和肛门温度 Tail skin and rectal temperature | 21 | 2.11 |
CT扫描骨形态计量学参数 Bone histomorphometric parameters by CT scan | 12 | 1.20 |
TUNEL染色检测脏器细胞凋亡 TUNEL staining of organ cell apoptosis | 11 | 1.10 |
免疫荧光法检测相关蛋白分布 Immunofluorescence assay for protein distribution | 9 | 0.90 |
戊巴比妥钠睡眠试验 Pentobarbital sodium sleep test | 7 | 0.70 |
代谢组学 Metabolomics | 6 | 0.60 |
肠道菌群 Intestinal flora | 5 | 0.50 |
X线测骨密度 Bone density measured by X-Ray | 5 | 0.50 |
原位杂交法检测相关mRNA表达 In situ hybridization of mRNA expression | 5 | 0.50 |
西医评价指标 Western medicine evaluation indexes | 频数/次 Frequency/time | 百分比/% Percentage/ % |
---|---|---|
阴道脱落细胞涂片 Shed cell of vaginal smears | 125 | 85.04 |
阴道脱落细胞涂片+血清雌二醇 Shed cell of vaginal smears and estradiol | 5 | 3.40 |
血清雌二醇 Serum estradiol | 5 | 3.40 |
行为学+一般情况 Behavioral and general condition | 1 | 0.68 |
阴道脱落细胞涂片+行为学 Shed cell of vaginal smears and behavioral obeservations | 5 | 3.40 |
阴道脱落细胞涂片+一般情况 Shed cell of vaginal smears and general condition | 3 | 2.04 |
阴道电阻法 Vaginal electrical resistance method | 1 | 0.68 |
尾部皮肤和肛门温度 Tail skin and anal temperature | 1 | 0.68 |
阴道脱落细胞涂片+肛温 Shed cell of vaginal smears and anal temperature | 1 | 0.68 |
表7 围绝经期综合征动物模型建立成功的西医评价指标分布
Table 7 Distribution of evaluation indexes for successful establishment of perimenopausal syndrome animal models in Western medicine
西医评价指标 Western medicine evaluation indexes | 频数/次 Frequency/time | 百分比/% Percentage/ % |
---|---|---|
阴道脱落细胞涂片 Shed cell of vaginal smears | 125 | 85.04 |
阴道脱落细胞涂片+血清雌二醇 Shed cell of vaginal smears and estradiol | 5 | 3.40 |
血清雌二醇 Serum estradiol | 5 | 3.40 |
行为学+一般情况 Behavioral and general condition | 1 | 0.68 |
阴道脱落细胞涂片+行为学 Shed cell of vaginal smears and behavioral obeservations | 5 | 3.40 |
阴道脱落细胞涂片+一般情况 Shed cell of vaginal smears and general condition | 3 | 2.04 |
阴道电阻法 Vaginal electrical resistance method | 1 | 0.68 |
尾部皮肤和肛门温度 Tail skin and anal temperature | 1 | 0.68 |
阴道脱落细胞涂片+肛温 Shed cell of vaginal smears and anal temperature | 1 | 0.68 |
分类 Categories | PS患者 PS patients | PS模型动物 PS animals |
---|---|---|
临床表现 | 同:均可出现情绪抑郁或急躁不安、失眠等精神神经症状和毛发稀疏脱落等表现 | |
Clinical manifestation | 异:涉及多系统病变,症状复杂,如同时出现潮热汗出、失眠等症状 | 异:症状不如人类明显,部分症状无法直接观察,如排尿困难、潮热汗出等,需通过检测相关指标来判断 |
病理学观察 | 同:均检测阴道脱落细胞涂片 | |
Pathological observations | 异:暂无相关研究 | 异:可见脏器有不同程度萎缩,部分细胞数量减少 |
生化指标 | 同:均出现激素水平异常,如促黄体生成素(luteinizing hormone,LH)、促卵泡激素(follicle stimulating hormone,FSH)升高,雌二醇(estradiol,E2)、5-羟色胺(5-hydroxytryptamine,5-HT)降低 | |
Biochemical indexes | 异:大部分仅检查血清性激素水平,即LH、 FSH升高,E2降低,绝经后FSH>40 U/L, 且E2<10~20 pg/mL提示卵巢功能衰竭 | 异:检测指标较人类多,增加性激素、神经递质、炎症因子等指标,如造模后动物体内的多巴胺(dopamine,DA)、白细胞介素-2(interleukin-2,IL-2)水平降低,促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)升高 |
影像学检查 | 同:CT或X线检查均可发现骨小梁稀疏,骨密度下降 | |
Imaging examination | 异:大部分仅通过CT或X线检查发现骨密度下降和骨小梁稀疏 | 异:部分实验采用X线检查发现骨小梁稀发且结构紊乱;CT检查发现骨形态计量学参数减低;电镜检查发现下丘脑线粒体和内质网损伤等 |
表8 围绝经期综合征患者与动物模型的疾病特征和检测指标比较
Table 8 Comparison of disease characteristics and detection indexes between perimenopausal syndrome patients and model animals
分类 Categories | PS患者 PS patients | PS模型动物 PS animals |
---|---|---|
临床表现 | 同:均可出现情绪抑郁或急躁不安、失眠等精神神经症状和毛发稀疏脱落等表现 | |
Clinical manifestation | 异:涉及多系统病变,症状复杂,如同时出现潮热汗出、失眠等症状 | 异:症状不如人类明显,部分症状无法直接观察,如排尿困难、潮热汗出等,需通过检测相关指标来判断 |
病理学观察 | 同:均检测阴道脱落细胞涂片 | |
Pathological observations | 异:暂无相关研究 | 异:可见脏器有不同程度萎缩,部分细胞数量减少 |
生化指标 | 同:均出现激素水平异常,如促黄体生成素(luteinizing hormone,LH)、促卵泡激素(follicle stimulating hormone,FSH)升高,雌二醇(estradiol,E2)、5-羟色胺(5-hydroxytryptamine,5-HT)降低 | |
Biochemical indexes | 异:大部分仅检查血清性激素水平,即LH、 FSH升高,E2降低,绝经后FSH>40 U/L, 且E2<10~20 pg/mL提示卵巢功能衰竭 | 异:检测指标较人类多,增加性激素、神经递质、炎症因子等指标,如造模后动物体内的多巴胺(dopamine,DA)、白细胞介素-2(interleukin-2,IL-2)水平降低,促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)升高 |
影像学检查 | 同:CT或X线检查均可发现骨小梁稀疏,骨密度下降 | |
Imaging examination | 异:大部分仅通过CT或X线检查发现骨密度下降和骨小梁稀疏 | 异:部分实验采用X线检查发现骨小梁稀发且结构紊乱;CT检查发现骨形态计量学参数减低;电镜检查发现下丘脑线粒体和内质网损伤等 |
1 | 世界中医药学会联合会, 中华中医药学会. 国际中医临床实践指南更年期综合征(2020-10-11)[J]. 世界中医药, 2021, 16(2): 190-192. DOI: 10.3969/j.issn.1673-7202.2021.02.002 . |
World Federation of Chinese Medicine Societies, China Association of Chinese Medicine. International guide to clinical practice of traditional Chinese medicine: climacteric syndrome (October-November, 2020)[J]. World Chin Med, 2021, 16(2): 190-192. DOI: 10.3969/j.issn.1673-7202.2021.02.002 . | |
2 | NUDY M, ARAGAKI A K, JIANG X Z, et al. The severity of individual menopausal symptoms, cardiovascular disease, and all-cause mortality in the Women's Health Initiative Observational Cohort[J]. Menopause, 2022, 29(12):1365-1374. DOI: 10.1097/GME.0000000000002089 . |
3 | NAPPI R E, KROLL R, SIDDIQUI E, et al. Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden[J]. Menopause, 2021, 28(8):875-882. DOI: 10.1097/GME.0000000000001793 . |
4 | 苗明三. 实验动物和动物实验技术[M]. 北京: 中国中医药出版社, 1997. |
MIAO M S. Laboratory animals and animal experimental techniques[M]. Beijing: China Press of Traditional Chinese Medicine, 1997. | |
5 | 范星宇, 廖晓倩, 王梓仪, 等. 基于数据挖掘的原发性痛经动物模型分析[J]. 中国实验方剂学杂志, 2023, 29(2):166-174. |
FAN X Y, LIAO X Q, WANG Z Y, et al. Primary dysmenorrhea animal models based on data mining[J]. Chin J Exp Tradit Med Formulae, 2023, 29(2):166-174. | |
6 | 辛伟, 徐欢, 杨倩, 等. 夏冬季节气温变化对绝经期大鼠尾温变化的影响研究[J]. 时珍国医国药, 2021, 32(4):1013-1016. DOI: 10.3969/j.issn.1008-0805.2021.04.71 . |
XIN W, XU H, YANG Q, et al. Effect of seasonal temperature change in Xia Dong on tail temperature change of menopausal rats[J]. Lishizhen Med Mater Med Res, 2021, 32(4):1013-1016. DOI: 10.3969/j.issn.1008-0805.2021.04.71 . | |
7 | 余庆涛, 葛亚中. 墨旱莲丹参覆盆子口服液对更年期阴虚内热型大鼠的药理影响研究[J]. 海峡药学, 2021, 33(12): 10-12. DOI: 10.3969/j.issn.1006-3765.2021.12.003 . |
YU Q T, GE Y Z. Effect of MoHanLian DanShen FuPengZi oral liquid on model rats about the imitating-syndrome of fever due to Yin-deficiency in menopause[J]. Strait Pharm J, 2021, 33(12): 10-12. DOI: 10.3969/j.issn.1006-3765.2021.12.003 . | |
8 | ZHANG F, CAO J Y, ZHANG X, et al. Efficacy of self-made Gengnian Decoction on phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin signaling pathway in perimenopausal rats[J]. J Tradit Chin Med, 2019, 39(6):861-866. |
9 | 谢冰颖, 谢丽华, 许惠娟, 等. 疏肝法对围绝经期综合征肝郁证模型大鼠卵巢黄体生成素受体及促卵泡生成素受体的影响[J]. 国际中医中药杂志, 2018, 40(2):143-147. DOI: 10.3760/cma.j.issn.1673-4246.2018.02.012 . |
XIE B Y, XIE L H, XU H J, et al. Effects of liver-soothing therapy on the luteotropic hormone receptor and follicle stimulating hormone receptor of perimenopausal syndrome rats with liver qi stagnation[J]. International J Tradit Chin Med, 2018, 40(2):143-147. DOI: 10.3760/cma.j.issn.1673-4246.2018.02.012 . | |
10 | 谢幸, 孔北华, 段涛. 妇产科学[M]. 9版. 北京: 人民卫生出版社, 2018. |
XIE X, KONG B H, DUAN Z. Obstetrics and gynecology[M]. 9th ed. Beijing: People's Health Publishing House, 2018. | |
11 | GERVAIS N J, VIECHWEG S S, MONG J A, et al. The middle-aged ovariectomized marmoset (Callithrix jacchus) as a model of menopausal symptoms: preliminary evidence[J]. Neuroscience, 2016, 337:1-8. DOI: 10.1016/j.neuroscience. 2016.08.056 . |
12 | 孙侠, 刘科, 杨林, 等. 6种常用 SPF 级大小鼠繁殖性能测定与分析[J]. 中国比较医学杂志, 2016, 26(10):9-13. DOI: 10.3969.j.issn.1671-7856.2016.10.003 . |
SUN X, LIU K, YANG L, et al. Measurement and analysis of the reproductive performance in six commonly used SPF mice and rats[J]. Chin J Comp Med, 2016, 26(10):9-13. DOI: 10.3969.j.issn.1671-7856.2016.10.003 . | |
13 | 王铁枫, 刘雁峰, 辛明蔚, 等. 交通心肾中药对更年期大鼠性激素及神经递质的影响[J]. 中华中医药杂志, 2018, 33(4):1340-1343. |
WANG T F, LIU Y F, XIN M W, et al. Effects of Jiaotong Xinshen Decoction of coordinating heart and kidney on sex hormone and neurotransmitters in climacteric rats[J]. China Ind Econ, 2018, 33(4):1340-1343. | |
14 | 马娴, 傅萍, 凌博越, 等. 自然衰老ICR小鼠围绝经期模型的建立与评价[J]. 中华中医药杂志, 2016, 31(6): 2394-2397. DOI: 10.3969/j.issn.1673-7717.2008.05.030 . |
MA X, FU P, LING B Y, et al. Establishment and evaluation of perimenopausal model of ICR mice with natural aging[J]. China J Tradit Chin Med Pharm, 2016, 31(6): 2394-2397. DOI: 10.3969/j.issn.1673-7717.2008.05.030 . | |
15 | 臧凯, 罗小光, 李伟, 等. 围绝经期综合征渐衰动物模型选择[J]. 贵州医科大学学报, 2017, 42(11):1262-1265. DOI: 10.19367/j.cnki.1000-2707.2017.11.005 . |
ZANG K, LUO X G, LI W, et al. Selection of fading animal models with perimenopausal syndrome[J]. J Guizhou Med Univ, 2017, 42(11):1262-1265. DOI: 10.19367/j.cnki.1000-2707.2017.11.005 . | |
16 | TIAN S, MIAO M S, LI X M, et al. Study on neuroendocrine-immune function of Phenylethanoid Glycosides of Desertliving Cistanche herb in perimenopausal rat model[J]. J Ethnopharmacol, 2019, 238:111884. DOI: 10.1016/j.jep. 2019.111884 . |
17 | 周勇, 陈刚. 二仙汤对围绝经期综合征模型大鼠卵巢中凋亡蛋白Bcl-2、Bax的作用研究[J]. 时珍国医国药, 2020, 31(2):320-323. DOI: 10.3969/j.issn.1008-0805.2020.02.020 . |
ZHOU Y, CHEN G. Effect of Erxian Decoction on apoptosis proteins bcl-2 and bax in ovary of perimenopausal syndrome model rats[J]. Lishizhen Med Mater Med Res, 2020, 31(2):320-323. DOI: 10.3969/j.issn.1008-0805.2020.02.020 . | |
18 | LI Y, MA H, LU Y, et al. Menoprogen, a TCM herbal formula for menopause, increases endogenous E2 in an aged rat model of menopause by reducing ovarian granulosa cell apoptosis[J]. Biomed Res Int, 2016, 2016:2574637. DOI: 10.1155/2016/2574637 . |
19 | WANG S W, WU F H, ZHANG Y B, et al. Ameliorating effect of Erxian decoction combined with Fructus Schisandrae chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat model[J]. Chin Med, 2016, 11:47. DOI: 10.1186/s13020-016-0117-6 . |
20 | 马娴, 傅萍, 凌博越, 等. 自然衰老法与卵巢去势法建立围绝经期小鼠模型的比较研究[J]. 中华中医药学刊, 2017, 35(3):551-554. DOI: 10.13193/j.issn.1673-7717.2017.03.010 . |
MA X, FU P, LING B Y, et al. Comparative study on the establishment of perimenopausal mouse model by natural aging method and ovariectomy method[J]. Chin Arch Tradit Chin Med, 2017, 35(3):551-554. DOI: 10.13193/j.issn.1673-7717.2017.03.010 . | |
21 | RODRIGUES-SANTOS I, KALIL-CUTTI B, ANSELMO-FRANCI J A. Low corticosterone response to stress in a perimenopausal rat model is associated with the hypoactivation of PaMP region of the paraventricular nucleus and can be corrected by exogenous progesterone supplementation[J]. Neuroendocrinology, 2022, 112(5):467-480. DOI: 10.1159/000518336 . |
22 | KIM D, LIU Q F, JEONG H J, et al. A modified formulation of sutaehwan ameliorates menopausal anxiety, depression and heart hypertrophy in the VCD-induced menopausal mouse model[J]. Biol Pharm Bull, 2019, 42(9):1471-1481. DOI: 10.1248/bpb.b19-00056 . |
23 | CHEN J M, WANG H H, DONG Z Y, et al. GnRH-a-induced perimenopausal rat modeling and black cohosh preparations' effect on rat's reproductive endocrine[J]. Front Endocrinol (Lausanne), 2021, 12:683552. DOI: 10.3389/fendo.2021.683552 . |
24 | 于鑫梅, 杨溢铎, 李佶. 超促排卵诱导制备大鼠围绝经期动物模型的研究[J]. 中华中医药杂志, 2020, 35(8):4211-4214. DOI: 10.3969/j.issn.1005-9903.2007.10.023 . |
YU X M, YANG Y D, LI J. Study on perimenopausal mice model induced by superovulation[J]. China J Tradit Chin Med Pharm, 2020, 35(8):4211-4214. DOI: 10.3969/j.issn.1005-9903.2007.10.023 . | |
25 | ZHOU X D, YANG X J, ZHENG Y, et al. Jie-yu pill, A proprietary herbal medicine, ameliorates mood disorder-like behavior and cognitive impairment in estrogen-deprived mice exposed to chronic unpredictable mild stress: implication for a potential therapy of menopause syndrome[J]. Front Psychiatry, 2020, 11:579995. DOI: 10.3389/fpsyt.2020.579995 . |
26 | LAN J J, WU C M, LIANG W N, et al. An effective treatment of perimenopausal syndrome by combining two traditional Prescriptions of Chinese botanical drugs[J]. Front Pharmacol, 2021, 12:744409. DOI: 10.3389/fphar.2021.744409 . |
27 | 刘旭, 马瑞红. 雌性大鼠增龄与卵巢储备功能之间的关系[J]. 中国妇幼保健, 2016, 31(23):5151-5153. DOI: 10.7620/zgfybj.j.issn.1001-4411.2016.01.93 . |
LIU X, MA R H. Relationship between aging and ovarian reserve function in female rats[J]. Matern Child Health Care China, 2016, 31(23):5151-5153. DOI: 10.7620/zgfybj.j.issn.1001-4411.2016.01.93 . | |
28 | LLIBEROS C, LIEW S H, ZAREIE P, et al. Evaluation of inflammation and follicle depletion during ovarian ageing in mice[J]. Sci Rep, 2021, 11(1):278. DOI: 10.1038/s41598-020-79488-4 . |
29 | ZINGUE S, MICHEL T, TCHATCHOU J, et al. Estrogenic effects of Ficus umbellata Vahl. (Moraceae) extracts and their ability to alleviate some menopausal symptoms induced by ovariectomy in Wistar rats[J]. J Ethnopharmacol, 2016, 179:332-344. DOI: 10.1016/j.jep.2016.01.004 . |
30 | 刘晓宇, 王娇, 钱欣, 等. 围绝经期大鼠动情周期变化的研究[J]. 哈尔滨医科大学学报, 2014(5):358-360. |
LIU X Y, WANG J, QIAN X, et al. Changes of estrous cycle of perimenopausal rats[J]. J Harbin Med Univ, 2014(5):358-360. | |
31 | BELLOFIORE N, GEORGE E, VOLLENHOVEN B, et al. Reproductive aging and menopause-like transition in the menstruating spiny mouse (Acomys cahirinus)[J]. Hum Reprod, 2021, 36(12):3083-3094. DOI: 10.1093/humrep/deab215 . |
32 | HABERMEHL T L, UNDERWOOD K B, WELCH K D, et al. Aging-associated changes in motor function are ovarian somatic tissue-dependent, but germ cell and estradiol independent in post-reproductive female mice exposed to young ovarian tissue[J]. GeroScience, 2022, 44(4):2157-2169. DOI: 10.1007/s11357-022-00549-9 . |
33 | ZHANG J F, SHAO S R, YE C H, et al. A clinical study of the effect of estradiol valerate on sleep disorders, negative emotions, and quality of life in perimenopausal women[J]. Evid Based Complement Alternat Med, 2021, 2021:8037459. DOI: 10.1155/2021/8037459 . |
34 | 葛容辉. 更年安片治疗妇女更年期综合征的临床效果观察[J]. 中国现代药物应用, 2020, 14(23):137-139. DOI: 10.14164/j.cnki.cn11-5581/r.2020.23.061 . |
GE R H. Clinical effect of Gengnian'an Tablets in the treatment of climacteric syndrome[J]. Chin J Modern Drug Application, 2020, 14(23):137-139. DOI: 10.14164/j.cnki.cn11-5581/r.2020.23.061 . | |
35 | 中华中医药学会中药实验药理专业委员会. 围绝经期综合征动物模型制备规范(草案)[J]. 中华中医药杂志, 2018, 33(3):996-1000. DOI: 10.3969/j.issn.1006-6179.2011.03.019 . |
Traditional Chinese Medicine Experimental Pharmacology Professional Committee, China Association of Chinese Medicine. Standard for preparation of animal model of perimenopausal syndrome (draft)[J]. China J Tradit Chin Med Pharm, 2018, 33(3):996-1000. DOI: 10.3969/j.issn.1006-6179.2011.03.019 . | |
36 | 李艺, 黄露, 王红. 血清性激素水平与更年期综合征的相关性[J]. 中国老年学杂志, 2020, 40(14):3042-3045. |
YI, LU H, HONG W. 血清性激素水平与更年期综合征的相关性[J]. Chin J Gerontol, 2020, 40(14):3042-3045. | |
37 | LI J L, HE P Y, ZHANG J, et al. Orcinol glucoside improves the depressive-like behaviors of perimenopausal depression mice through modulating activity of hypothalamic-pituitary-adrenal/ovary axis and activating BDNF- TrkB-CREB signaling pathway[J]. Phytother Res, 2021, 35(10):5795-5807. DOI: 10.1002/ptr.7237 . |
38 | TANG B X, MENG Q Y, XIE C, et al. Ziyin Bushen Decoction alleviates perimenopausal syndrome in rats by enhancing estradiol production[J]. Evid Based Complement Alternat Med, 2020, 2020:8895809. DOI: 10.1155/2020/8895809 . |
39 | JIANG H, BAI W P, WANG W J, et al. Proteomics in plasma of ovariectomized rats and those exposed to estradiol valerate[J]. J Steroid Biochem Mol Biol, 2018, 178:1-12. DOI: 10.1016/j.jsbmb.2017.10.015 . |
40 | WU X G, KIM M J, YANG H J, et al. Chitosan alleviated menopausal symptoms and modulated the gut microbiota in estrogen-deficient rats[J]. Eur J Nutr, 2021, 60(4):1907-1919. DOI: 10.1007/s00394-020-02382-2 . |
41 | 石玉梅, 李诗哲, 耿佃涛, 等. 围绝经期及绝经后女性血红蛋白和血脂与骨质疏松的相关性[J]. 中国骨质疏松杂志, 2023, 29(2):195-198, 208. DOI: 10.3969/j.issn.1006-7108.2023.02.008 . |
SHI Y M, LI S Z, GENG D T, et al. Relationship between hemoglobin and blood lipids and osteoporosis in perimenopausal and postmenopausal women[J]. Chin J Osteoporos, 2023, 29(2):195-198, 208. DOI: 10.3969/j.issn.1006-7108.2023.02.008 . | |
42 | 杨文佳, 赵娜, 于心同, 等. "补肾安神"法针刺治疗肾阴虚型围绝经期失眠: 随机对照试验[J]. 中国针灸, 2023, 43(6):634-638. |
YANG W J, ZHAO N, YU X T, et al. Bushen Anshen acupuncture for perimenopausal insomnia of kidney-Yin deficiency: a randomized controlled trial[J]. Chin Acupunct Moxibustion, 2023, 43(6):634-638. | |
43 | LEE E, JANG M, LIM T G, et al. Selective activation of the estrogen receptor-β by the polysaccharide from Cynanchum wilfordii alleviates menopausal syndrome in ovariectomized mice[J]. Int J Biol Macromol, 2020, 165(Pt A):1029-1037. DOI: 10.1016/j.ijbiomac.2020.09.165 . |
44 | LEE M, PARK S J, MOON Y J, et al. Combination of Sargassum fusiforme and Pueraria lobata extracts alleviates postmenopausal symptoms in ovariectomized rats[J]. J Med Food, 2020, 23(7):735-744. DOI: 10.1089/jmf.2019.4555 . |
45 | CHEN X Q, WU C M, LIANG W N, et al. The metabolomic rationale for treating perimenopausal syndrome as kidney deficiency[J]. Evid Based Complement Alternat Med, 2020, 2020:8568353. DOI: 10.1155/2020/8568353 . |
46 | 阮璐薇, 张鹏横, 黄睿婷, 等. 去势法联合慢性不可预知性温和应激法建立围绝经期综合征肝郁证动物模型的研究[J]. 中华中医药杂志, 2021, 36(1):394-397. |
RUAN L W, ZHANG P H, HUANG R T, et al. Castration combined with chronic unpredictable mild stress to establish animal model of liver depression pattern of perimenopausal syndrome[J]. China Ind Econ, 2021, 36(1):394-397. | |
47 | 赵元, 郑红霞, 徐颖, 等. 青盐方治疗围绝经期焦虑症的网络分析及实验验证[J]. 中国中药杂志, 2020, 45(17):4129-4139. DOI: 10.19540/j.cnki.cjcmm.20200622.401 . |
ZHAO Y, ZHENG H X, XU Y, et al. Network analysis and experimental verification of Qingyan Formula in treatment of perimenopausal anxiety disorder[J]. China J Chin Materia Med, 2020, 45(17):4129-4139. DOI: 10.19540/j.cnki.cjcmm.20200622.401 . | |
48 | 唐雨晴, 张东伟, 孙雪娇, 等. 补肾活血方对去卵巢大鼠子宫ER及Cyclin B表达影响的实验研究[J]. 北京中医药大学学报, 2016, 39(4):281-287. DOI: 10.3969/j.issn.1006-2157.2016.04.004 . |
TANG Y Q, ZHANG D W, SUN X J, et al. Effects of Bushen Huoxue Formula on estrogen receptor and Cyclin B in uteri of ovariectomized rats[J]. J Beijing Univ Tradit Chin Med, 2016, 39(4):281-287. DOI: 10.3969/j.issn.1006-2157.2016.04.004 . | |
49 | 闫丽, 温和, 唐桂毅, 等. 大鼠阴道细胞涂片不同染色方法在动情周期判定中的价值[J]. 药物评价研究, 2020, 43(1):72-76. DOI: 10.7501/j.issn.1674-6376.2020.01.012 . |
YAN L, WEN H, TANG G Y, et al. Diagnostic value of three staining methods for rat vaginal cell smears in determination of estrous cycle[J]. Drug Eval Res, 2020, 43(1):72-76. DOI: 10.7501/j.issn.1674-6376.2020.01.012 . | |
50 | CHEUNG H P, WANG S W, NG T B, et al. Comparison of chemical profiles and effectiveness between Erxian Decoction and mixtures of decoctions of its individual herbs: a novel approach for identification of the standard chemicals[J]. Chin Med, 2017, 12:1. DOI: 10.1186/s13020-016-0123-8 . |
51 | 赵磊, 黄赫, 慕杨娜, 等. 济阴颗粒对围绝经期综合征大鼠卵巢Caspase依赖性细胞凋亡通路的影响[J]. 北京中医药大学学报, 2018, 41(5):372-375. DOI: 10.3969/j.issn.1006-2157.2018.05.004 . |
ZHAO L, HUANG H, MU Y N, et al. Influence of Jiyin Capsule on apoptosis pathway of ovarian caspase de-pendent cells in rats with peri-menopausal syndrome[J]. J Beijing Univ Tradit Chin Med, 2018, 41(5):372-375. DOI: 10.3969/j.issn.1006-2157.2018.05.004 . | |
52 | PARK D R, YEO C H, YOON J E, et al. Polygonatum sibiricum improves menopause symptoms by regulating hormone receptor balance in an ovariectomized mouse model[J]. Biomed Pharmacother, 2022, 153:113385. DOI: 10.1016/j.biopha.2022.113385 . |
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