Laboratory Animal and Comparative Medicine ›› 2024, Vol. 44 ›› Issue (1): 74-84.DOI: 10.12300/j.issn.1674-5817.2023.062
• Animal Models of Human Diseases • Previous Articles Next Articles
Tianwei LIANG, Yasheng DENG, Hui HUANG, Na RONG, Xin LIU, Yujie WANG, Jiang LIN()(
)
Received:
2023-05-11
Revised:
2023-08-04
Online:
2024-02-25
Published:
2024-02-25
Contact:
Jiang LIN
CLC Number:
Tianwei LIANG,Yasheng DENG,Hui HUANG,et al. Preparation Methods and Evaluation Criteria Analysis of Animal Models for Perimenopausal Syndrome[J]. Laboratory Animal and Comparative Medicine, 2024, 44(1): 74-84. DOI: 10.12300/j.issn.1674-5817.2023.062.
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URL: https://www.slarc.org.cn/dwyx/EN/10.12300/j.issn.1674-5817.2023.062
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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