Laboratory Animal and Comparative Medicine ›› 2024, Vol. 44 ›› Issue (4): 405-418.DOI: 10.12300/j.issn.1674-5817.2024.012
• Animal Models of Human Diseases • Previous Articles Next Articles
ZHENG Yiqing, DENG Yasheng, FAN Yanping, LIANG Tianwei, HUANG Hui, LIU Yonghui, NI Zhaobing, LIN Jiang()(
)
Received:
2024-01-22
Revised:
2024-04-07
Online:
2024-08-25
Published:
2024-09-06
Contact:
LIN Jiang
CLC Number:
ZHENG Yiqing,DENG Yasheng,FAN Yanping,et al. Application Analysis of Animal Models for Pelvic Inflammatory Disease Based on Data Mining[J]. Laboratory Animal and Comparative Medicine, 2024, 44(4): 405-418. DOI: 10.12300/j.issn.1674-5817.2024.012.
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URL: https://www.slarc.org.cn/dwyx/EN/10.12300/j.issn.1674-5817.2024.012
造模动物 Modeling animals | 频数(百分比/%) Frequency (percentage/%) | 体重/g Body weight/g |
---|---|---|
SD 大鼠 SD rats | 155 (71.76) | 以(200±20)g为主 |
Wistar 大鼠 Wistar rats | 43 (19.91) | 以(200±20)g为主 |
BALB/c 小鼠 BALB/c mice | 8 (3.70) | 以(20±1)g为主 |
新西兰白兔 New Zealand white rabbits | 3 (1.39) | 文献未提及 |
C57BL/6 小鼠 C57BL/6 mice | 4 (1.85) | 以(19±1)g为主 |
ICR 小鼠 ICR mice | 2 (0.93) | 以(21±1)g为主 |
FVB野生型小鼠 FVB wild-type mice | 1 (0.46) | 文献未提及 |
Table 1 Frequency distribution of animal species used in pelvic inflammatory disease (PID) models
造模动物 Modeling animals | 频数(百分比/%) Frequency (percentage/%) | 体重/g Body weight/g |
---|---|---|
SD 大鼠 SD rats | 155 (71.76) | 以(200±20)g为主 |
Wistar 大鼠 Wistar rats | 43 (19.91) | 以(200±20)g为主 |
BALB/c 小鼠 BALB/c mice | 8 (3.70) | 以(20±1)g为主 |
新西兰白兔 New Zealand white rabbits | 3 (1.39) | 文献未提及 |
C57BL/6 小鼠 C57BL/6 mice | 4 (1.85) | 以(19±1)g为主 |
ICR 小鼠 ICR mice | 2 (0.93) | 以(21±1)g为主 |
FVB野生型小鼠 FVB wild-type mice | 1 (0.46) | 文献未提及 |
造模因素 Modelling factors | 造模方法 Modelling methods | 频数(百分比/%) Frequency (percentage/%) |
---|---|---|
化学因素造模 Chemical factor modelling | 苯酚胶浆法 | 59 (27.19) |
盐酸和脂多糖法 | 6 (2.77) | |
物理因素造模 Physical factor modelling | 宫腔无菌异物法 | 4 (1.84) |
生物因素造模 Biological factor modelling | 单一细菌或微生物法 | 9 (4.15) |
混合细菌感染法 | 42 (19.35) | |
双重因素造模 Dual-factor modelling | 机械损伤+混合细菌感 染法 | 80 (36.87) |
苯酚凝胶+机械损伤法 | 12 (5.53) | |
苯酚凝胶+异物法 | 1 (0.46) | |
苯酚凝胶+细菌感染法 | 1 (0.46) | |
多因素造模 Multi-factor modelling | 饥饿+疲劳干预联合细 菌感染法 | 3 (1.38) |
Table 2 Classification and frequency distribution of animal modelling methods for pelvic inflammatory disease (PID)
造模因素 Modelling factors | 造模方法 Modelling methods | 频数(百分比/%) Frequency (percentage/%) |
---|---|---|
化学因素造模 Chemical factor modelling | 苯酚胶浆法 | 59 (27.19) |
盐酸和脂多糖法 | 6 (2.77) | |
物理因素造模 Physical factor modelling | 宫腔无菌异物法 | 4 (1.84) |
生物因素造模 Biological factor modelling | 单一细菌或微生物法 | 9 (4.15) |
混合细菌感染法 | 42 (19.35) | |
双重因素造模 Dual-factor modelling | 机械损伤+混合细菌感 染法 | 80 (36.87) |
苯酚凝胶+机械损伤法 | 12 (5.53) | |
苯酚凝胶+异物法 | 1 (0.46) | |
苯酚凝胶+细菌感染法 | 1 (0.46) | |
多因素造模 Multi-factor modelling | 饥饿+疲劳干预联合细 菌感染法 | 3 (1.38) |
疾病模型类型 Disease model type | 造模周期/d Modelling cycle/d | 频数(百分比/%) Frequency (percentage/%) | 给药时间/d Administration time/d | 频数(百分比/%) Frequency (percentage/%) |
---|---|---|---|---|
急性盆腔炎 Acute pelvic inflammatory disease(APID) | ≤7 | 9 (4.09) | ≤7 | 11 (4.89) |
8~14 | 10 (4.55) | 8~14 | 4 (1.78) | |
15~21 | 2 (0.91) | 15~21 | 7 (3.11) | |
>28 | 2 (0.91) | 22~28 | 1 (0.45) | |
慢性盆腔炎/盆腔炎性疾病后遗症 Chronic pelvic inflammatory disease (CPID)/ sequelae of pelvic inflammatory disease(SPID) | ≤7 | 45 (20.46) | ≤7 | 17 (7.56) |
8~14 | 47 (21.36) | 8~14 | 45 (20.00) | |
15~21 | 24 (10.45) | 15~21 | 74 (32.89) | |
22~28 | 4 (1.82) | 22~28 | 20 (8.89) | |
>28 | 27 (12.27) | >28 | 10 (4.44) | |
不明确分期的盆腔炎 Pelvic inflammatory disease with unclear staging | ≤7 | 26 (11.81) | ≤7 | 4 (1.78) |
8~14 | 10 (4.55) | 8~14 | 10 (4.44) | |
15~21 | 10 (4.55) | 15~21 | 16 (7.11) | |
22~28 | 1 (0.45) | 22~28 | 3 (1.33) | |
>28 | 4 (1.82) | >28 | 3 (1.33) |
Table 3 Frequency distribution of modelling cycles and administration duration for pelvic inflammatory disease (PID) animal modelling
疾病模型类型 Disease model type | 造模周期/d Modelling cycle/d | 频数(百分比/%) Frequency (percentage/%) | 给药时间/d Administration time/d | 频数(百分比/%) Frequency (percentage/%) |
---|---|---|---|---|
急性盆腔炎 Acute pelvic inflammatory disease(APID) | ≤7 | 9 (4.09) | ≤7 | 11 (4.89) |
8~14 | 10 (4.55) | 8~14 | 4 (1.78) | |
15~21 | 2 (0.91) | 15~21 | 7 (3.11) | |
>28 | 2 (0.91) | 22~28 | 1 (0.45) | |
慢性盆腔炎/盆腔炎性疾病后遗症 Chronic pelvic inflammatory disease (CPID)/ sequelae of pelvic inflammatory disease(SPID) | ≤7 | 45 (20.46) | ≤7 | 17 (7.56) |
8~14 | 47 (21.36) | 8~14 | 45 (20.00) | |
15~21 | 24 (10.45) | 15~21 | 74 (32.89) | |
22~28 | 4 (1.82) | 22~28 | 20 (8.89) | |
>28 | 27 (12.27) | >28 | 10 (4.44) | |
不明确分期的盆腔炎 Pelvic inflammatory disease with unclear staging | ≤7 | 26 (11.81) | ≤7 | 4 (1.78) |
8~14 | 10 (4.55) | 8~14 | 10 (4.44) | |
15~21 | 10 (4.55) | 15~21 | 16 (7.11) | |
22~28 | 1 (0.45) | 22~28 | 3 (1.33) | |
>28 | 4 (1.82) | >28 | 3 (1.33) |
检测指标 Detection indicator | 频数(百分比/%) Frequency (percentage/%) |
---|---|
HE染色观察组织病理变化 Histopathological changes using HE staining | |
子宫Uterus | 132 (14.49) |
输卵管Oviduct | 19 (2.09) |
卵巢Ovary | 7 (0.77) |
阴道Vagina | 3 (0.33) |
盆腔Pelvic cavity | 2 (0.22) |
脾脏Spleen | 1 (0.11) |
ELISA检测血清相关指标ELISA detection of serum⁃related indicators | 130 (14.27) |
肉眼观察组织外观变化Changes in tissue morphology observed with the naked eye | 94 (10.32) |
蛋白质印迹法检测组织中相关蛋白表达Western blot detection of related protein expression in tissues | 65 (7.14) |
免疫组织化学法检测组织中相关蛋白表达、病理评分/分级Immunohistochemical detection of related protein expression, pathological scoring/grading in tissues | 57 (6.26) |
脏器指数/系数 Organ index/coefficient | |
子宫 Uterus | 26(2.85) |
卵巢 Ovary | 4(0.44) |
脾脏 Spleen | 6(0.66) |
胸腺 Thymus | 4(0.44) |
肝脏 Liver | 1(0.11) |
聚合酶链式反应检测组织相关指标的mRNA含量Polymerase chain reaction (PCR) for the detection of mRNA content of tissue-related indicators | |
逆转录PCR Reverse transcription PCR | 18 (1.98) |
实时荧光定量PCR Real-time fluorescence quantitative PCR | 15 (1.65) |
实时荧光定量逆转录PCR Real-time fluorescence quantitative reverse transcription PCR | 6 (0.66) |
肿胀度/肿胀率/抑制率 Swelling degree/Swelling rate/Inhibition rate | 32 (3.51) |
ELISA检测组织相关指标 ELISA detection of tissue-related indicators | 29 (3.18) |
血液流变学指标、氧化应激指标 Blood rheology indices, oxidative stress indices | 24 (2.63) |
一般状况 General condition | 18 (1.98) |
体重 Body weight | 16 (1.76) |
血常规 Complete blood count | 15 (1.65) |
流式细胞仪 Flow cytometry | 14 (1.54) |
阴道涂片 Vaginal smear | 10 (1.10) |
免疫荧光、小鼠疼痛评分Immunofluorescence, mouse grimace scale | 6 (0.66) |
马松染色法、NO含量测定 Masson staining method, measurement of NO content | 5 (0.55) |
Table 4 Classification and frequency distribution of high-frequency detection indicators in pelvic inflammatory disease (PID) animal models
检测指标 Detection indicator | 频数(百分比/%) Frequency (percentage/%) |
---|---|
HE染色观察组织病理变化 Histopathological changes using HE staining | |
子宫Uterus | 132 (14.49) |
输卵管Oviduct | 19 (2.09) |
卵巢Ovary | 7 (0.77) |
阴道Vagina | 3 (0.33) |
盆腔Pelvic cavity | 2 (0.22) |
脾脏Spleen | 1 (0.11) |
ELISA检测血清相关指标ELISA detection of serum⁃related indicators | 130 (14.27) |
肉眼观察组织外观变化Changes in tissue morphology observed with the naked eye | 94 (10.32) |
蛋白质印迹法检测组织中相关蛋白表达Western blot detection of related protein expression in tissues | 65 (7.14) |
免疫组织化学法检测组织中相关蛋白表达、病理评分/分级Immunohistochemical detection of related protein expression, pathological scoring/grading in tissues | 57 (6.26) |
脏器指数/系数 Organ index/coefficient | |
子宫 Uterus | 26(2.85) |
卵巢 Ovary | 4(0.44) |
脾脏 Spleen | 6(0.66) |
胸腺 Thymus | 4(0.44) |
肝脏 Liver | 1(0.11) |
聚合酶链式反应检测组织相关指标的mRNA含量Polymerase chain reaction (PCR) for the detection of mRNA content of tissue-related indicators | |
逆转录PCR Reverse transcription PCR | 18 (1.98) |
实时荧光定量PCR Real-time fluorescence quantitative PCR | 15 (1.65) |
实时荧光定量逆转录PCR Real-time fluorescence quantitative reverse transcription PCR | 6 (0.66) |
肿胀度/肿胀率/抑制率 Swelling degree/Swelling rate/Inhibition rate | 32 (3.51) |
ELISA检测组织相关指标 ELISA detection of tissue-related indicators | 29 (3.18) |
血液流变学指标、氧化应激指标 Blood rheology indices, oxidative stress indices | 24 (2.63) |
一般状况 General condition | 18 (1.98) |
体重 Body weight | 16 (1.76) |
血常规 Complete blood count | 15 (1.65) |
流式细胞仪 Flow cytometry | 14 (1.54) |
阴道涂片 Vaginal smear | 10 (1.10) |
免疫荧光、小鼠疼痛评分Immunofluorescence, mouse grimace scale | 6 (0.66) |
马松染色法、NO含量测定 Masson staining method, measurement of NO content | 5 (0.55) |
阳性对照药 Positive control drug | 剂量范围/(g·kg-1) Dose range/ (g·kg-1) | 频数(百分比/%) Frequency (percentage/%) |
---|---|---|
妇科千金片Fuke Qianjin Tablets | 0.15~3.6 | 44 (23.15) |
金刚藤胶囊Jingangteng Capsules | 0.067~16.2 | 17 (8.94) |
妇炎康片Fuyankang Tablets | 0.042~5.2 | 16 (8.42) |
康妇炎胶囊、左氧氟沙星Kangfuyan Capsules, Levofloxacin | 0.025~9.3; 0.03~0.08 | 13 (6.84) |
醋酸地塞米松Dexamethasone acetate | 1.35×10-4~1.82 | 10 (5.26) |
阿司匹林Aspirin | 2×10-4~20 | 9 (4.73) |
妇乐片Fule Tablets | 0.65~2.5 | 8 (4.21) |
桂枝茯苓胶囊、罗红霉素Guizhi Fuling Capsules, Roxithromycin | 0.12~3; 82.74×10-3 | 5 (2.63) |
阿奇霉素、甲硝唑Azithromycin, Metronidazole | 1.7×10-3~6; 0.02~0.04 | 4 (2.10) |
花红颗粒、蒲苓盆炎康颗粒、人胎盘组织液、少腹逐瘀颗粒、康妇消炎栓、金鸡颗粒 Huahong Granules, Puling Penyankang Granules, Human Placenta Tissue Hydrolysate, Shaofu Zhuyu Granules, Kangfu Xiaoyan Suppository, Jinji Granules | 2.7~8.4; 3.15×10-3~3; 1; 0.364~1.5; 5.04; 1.02~27.4 | 3 (1.58) |
头孢克肟胶囊、妇炎消胶囊、克林霉素、庆大霉素、盆炎净胶囊 Cefixime Capsules, Fuyanxiao Capsules, Clindamycin, Gentamicin, Penyanjing Capsules | 0.067 5; 0.95; 0.01~0.04; 1.44×10-4; 0.54~3.24 | 2 (1.05) |
布洛芬、阿莫西林、TLR4抑制剂、坤复康片、依帕司他、泼尼松龙、羧甲基纤维素钠、妇科白带片、妇炎净 颗粒、抑菌方、抗炎方、补益方、蒙药赤瓟子、徐长卿 Ibuprofen, Amoxicillin, TLR4 inhibitors, Kunfukang Tablets, Epalrestat, Prednisolone, Sodium Carboxymethyl Cellulose, Fuke Baidai Tablets, Fuyanjing Granulas, Yijun Formula, Kangyan Formula, Buyi Formula, Mongolian Medicine Chipaozi, Cynanchum paniculatum | 0.07; 0.2; 1×10-3; 0.65; 0.02; 1.7×10-3; 20; 0.225; 1.2; 2.7; 2.7; 2.7; 1.04; 0.15 | 1 (0.53) |
Table 5 Positive control drugs for pelvic inflammatory disease (PID) animal models
阳性对照药 Positive control drug | 剂量范围/(g·kg-1) Dose range/ (g·kg-1) | 频数(百分比/%) Frequency (percentage/%) |
---|---|---|
妇科千金片Fuke Qianjin Tablets | 0.15~3.6 | 44 (23.15) |
金刚藤胶囊Jingangteng Capsules | 0.067~16.2 | 17 (8.94) |
妇炎康片Fuyankang Tablets | 0.042~5.2 | 16 (8.42) |
康妇炎胶囊、左氧氟沙星Kangfuyan Capsules, Levofloxacin | 0.025~9.3; 0.03~0.08 | 13 (6.84) |
醋酸地塞米松Dexamethasone acetate | 1.35×10-4~1.82 | 10 (5.26) |
阿司匹林Aspirin | 2×10-4~20 | 9 (4.73) |
妇乐片Fule Tablets | 0.65~2.5 | 8 (4.21) |
桂枝茯苓胶囊、罗红霉素Guizhi Fuling Capsules, Roxithromycin | 0.12~3; 82.74×10-3 | 5 (2.63) |
阿奇霉素、甲硝唑Azithromycin, Metronidazole | 1.7×10-3~6; 0.02~0.04 | 4 (2.10) |
花红颗粒、蒲苓盆炎康颗粒、人胎盘组织液、少腹逐瘀颗粒、康妇消炎栓、金鸡颗粒 Huahong Granules, Puling Penyankang Granules, Human Placenta Tissue Hydrolysate, Shaofu Zhuyu Granules, Kangfu Xiaoyan Suppository, Jinji Granules | 2.7~8.4; 3.15×10-3~3; 1; 0.364~1.5; 5.04; 1.02~27.4 | 3 (1.58) |
头孢克肟胶囊、妇炎消胶囊、克林霉素、庆大霉素、盆炎净胶囊 Cefixime Capsules, Fuyanxiao Capsules, Clindamycin, Gentamicin, Penyanjing Capsules | 0.067 5; 0.95; 0.01~0.04; 1.44×10-4; 0.54~3.24 | 2 (1.05) |
布洛芬、阿莫西林、TLR4抑制剂、坤复康片、依帕司他、泼尼松龙、羧甲基纤维素钠、妇科白带片、妇炎净 颗粒、抑菌方、抗炎方、补益方、蒙药赤瓟子、徐长卿 Ibuprofen, Amoxicillin, TLR4 inhibitors, Kunfukang Tablets, Epalrestat, Prednisolone, Sodium Carboxymethyl Cellulose, Fuke Baidai Tablets, Fuyanjing Granulas, Yijun Formula, Kangyan Formula, Buyi Formula, Mongolian Medicine Chipaozi, Cynanchum paniculatum | 0.07; 0.2; 1×10-3; 0.65; 0.02; 1.7×10-3; 20; 0.225; 1.2; 2.7; 2.7; 2.7; 1.04; 0.15 | 1 (0.53) |
模型病变机制 Model lesion mechanism | 相关指标变化 Changes in relevant indicators |
---|---|
炎性反应 Inflammatory reaction | (1)促炎因子:肿瘤坏死因子(TNF)↑,白细胞介素(IL)-1β↑,IL-2↑,IL-6↑,IL-8↑,IL-17A↑,IL-17F↑,IL-18↑; (2)抑炎因子:IL-4↓,IL-10↓,IL-12↓,IL-13↓; (3)炎症细胞:白细胞↑,单核细胞↑,嗜酸性粒细胞↑,中性粒细胞↑,淋巴细胞↑; (4)其他炎症相关:单核细胞趋化蛋白-1(MCP-1)↑,趋化因子1(CXCL1)↑,巨噬细胞炎症蛋白-2(MIP-2)↑,一氧化氮(NO)↑,γ干扰素(IFN-γ)↓,环氧化酶-2(COX-2)↑,前列腺素E2(PGE2)↑,组胺↑,血栓素B2(TXB2)↑,6-酮-前列腺素F1α/TXB2↑,血管生成素-2(Ang-2)↑,骨桥蛋白(OPN)↑,调节激活正常T细胞表达分泌因子(RANTES)↑,髓过氧化物酶(MPO)↑,血管细胞间黏附分子1(VCAM-1)↑,内皮素-1(ET-1)↑,可溶性尿激酶型纤溶酶原激活物受体(suPAR)↑,磷脂酰肌醇-3激酶(PI3K)↑,丝苏氨酸激酶(AKT)↑,C反应蛋白(CRP)↑,超敏(hs)-CRP↑;核转录因子-κB(NF-κB)↑,IκB激酶α(IκKα)↑,IKβ激酶(IκKβ)↑,磷酸化NF-κB抑制蛋白α(p-IκBα)↑,NF-κB p50↑,NF-κB p65↑,磷酸化NF-κB-p65↑,c-Jun氨基末端激酶(JNK)↑,磷酸化JNK↑, p38丝裂原活化蛋白激酶(p38MAPK)↑,Smad2↑、Smad 3↑,Smad 7↓;Toll样受体(TLR)2↑,TLR4↑,髓样分化因子88(MyD88)↑,自噬效应蛋白1(Beclin-1)↑,微管相关蛋白轻链3Ⅱ(LC3-Ⅱ)↑,核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)↑,磷酸化酪氨酸激酶2(p-JAK2)↑,信号转导与转录激活因子1(STAT1)↑,磷酸化STAT3↑,细胞因子信号转导抑制因子1(SOCS1)↑,活化STAT蛋白质抑制因子3(PIAS3)↑;磷酸化AKT↑, 磷酸化κB抑制蛋白激酶α/β(p-IKKα/β)↑,磷脂酶Cβ(PLCβ)、磷脂酶C-γ1(PLC-γ1)和蛋白激酶C(PKC)↑,细胞外调节蛋白激酶(ERK)↑; (5)炎症、粘连等相关信号通路:①TLR4/髓样分化因子88(MyD88)/NF-κB信号通路中,TLR4↑、MyD88↑;②成纤维细胞生长因子(FGF)-2/激活FGF-2的受体1(FGFR1)信号通路中,PGE2↑、组胺↑,FGFR1↑,FGF-2↑;③NF-κB/TGF-β1/Smads信号通路中,NF-κB p65↑,TGF-β1↑,Smad 2↑,Smad 3↑,Smad7↓;④TLRs的信号转导途径之一PI3K/AKT信号通路中PI3K↑,AKT↑;⑤MAPK信号通路之JNK、p38信号通路中JNK↑,p38↑,p-JNK↑,p-p38↑;⑥JAK2/STAT3信号通路中,p-JAK2↑,p-STAT3↑,SOCS1↑,PIAS3↑;⑦JAK2/STAT1信号通路中,p-JAK2↑,p-STAT1↑,SOCS1↑,PIAS3↑;⑧ PLC/PKC信号通路中,PLC-β3↑,PLC-γ1和PKC的磷酸化↑;⑨ TLR4/NFκB/COX2信号通路中,TLR4↑,NF-κB↑,COX2↑[ |
氧化应激损伤Oxidative stress damage | 丙二醛↑,总抗氧化能力↓,超氧化物歧化酶↓,一氧化氮合酶(NOS)↑[ |
细胞凋亡 Apoptosis | 含半胱氨酸的天冬氨酸蛋白水解酶(caspase)-3↑,caspase-8↑,切割型caspase-3↑,切割型caspase-8↑,caspase-1↑;凋亡相关斑点样蛋白(ASC)↑,前B细胞克隆增强因子(PBEF)↑,Bcl-xl↑,Bcl-2关联的X蛋白(BAX)↑,B淋巴细胞瘤-2(BCL-2)↓,自杀相关因子↑,自杀相关因子配体(FasL)↑,肿瘤抑制基因(p53)↑,程序性死亡受体-1(PD-1)↓,程序性死亡受体配体-1(PD-L1)↓,TNF受体1(TNFR-1)↑,葡萄糖调节反应蛋白78(GRP78)↑,CCAAT增强子结合蛋白同源蛋白(CHOP)↑,TUNEL细胞凋亡率↑[ |
组织增生、粘连及纤维化 Tissue proliferation, adhesion,and fibrosis | 转化生长因子-β1↑,细胞间黏附分子-1↑,FGF2↑,胰岛素样生长因子-1(IGF-1)↑,Ⅰ型胶原蛋白↑,结缔组织生长因子↑,纤溶酶原激活剂抑制因子-1↑,组织型纤溶酶原激活剂(t PA)↓, 血管内皮生长因子(VEGF)↑,表皮生长因子(EGF)↓,黏蛋白-1(MUC-1)↓,基质血小板衍化生长因子(PDGF)↑,基质金属蛋白酶(MMP)2↑,MMP-9↑,金属蛋白酶抑制因子↑,磷酸化细胞外调节蛋白激酶(p-Erk1/2)↑,整合素αVβ3↓,同源框基因A10(HOXA10)↓,Ⅱ型TGF-β受体(TβRⅡ)↑[ |
免疫系统平衡失调 Imbalance of immune system | (1)免疫球蛋白:免疫球蛋白(Ig)A、IgG、IgM↓,分泌型IgA↓; (2)红细胞免疫指标检测:红细胞C3b受体花环率↓,红细胞免疫复合物花环率↑,细胞免疫黏附促进率(RFER)↓,红细胞免疫黏附抑制(RFIR)↑; (3)免疫细胞功能:CD4+CD25+调节性T细胞↑,CD4+↑,CD8+↓,自然杀伤性T细胞↓, CD3+↓,CD4+/CD8+↓, T细胞百分率、淋转率↓,自然杀伤(NK)细胞↓,调节性T细胞↓,辅助性T细胞17↑,辅助性T淋巴细胞(Th)、细胞毒性T淋巴细胞(Tc)、CD8细胞↑;巨噬细胞吞噬能力↓,血清总补体↓[ |
血液流变异常 Hemorheological abnormalities | 全血黏度低中高切↑,血浆黏度↑、红细胞聚集指数↑、全血高切相对指数↑、全血低切相对指数↑,还原黏度低中高切↑,红细胞压积↑,红细胞刚性指数↑、变形指数↑、电泳时间↑,全血卡松黏度和血小板聚集率↑,血沉和血沉方程K值↑[ |
肝肾功能障碍 Liver and kidney dysfunction | 促肾上腺皮质激素释放激素↑,促肾上腺皮质激素↑,肾上腺皮质酮↑,丙氨酸转氨酶↑,白蛋白↑,天冬氨酸转氨酶↑,碱性磷酸酶↑,肌酐↑,葡萄糖↑[ |
Table 6 Laboratory-related examination indicators for preparation of pelvic inflammatory disease (PID) animal models
模型病变机制 Model lesion mechanism | 相关指标变化 Changes in relevant indicators |
---|---|
炎性反应 Inflammatory reaction | (1)促炎因子:肿瘤坏死因子(TNF)↑,白细胞介素(IL)-1β↑,IL-2↑,IL-6↑,IL-8↑,IL-17A↑,IL-17F↑,IL-18↑; (2)抑炎因子:IL-4↓,IL-10↓,IL-12↓,IL-13↓; (3)炎症细胞:白细胞↑,单核细胞↑,嗜酸性粒细胞↑,中性粒细胞↑,淋巴细胞↑; (4)其他炎症相关:单核细胞趋化蛋白-1(MCP-1)↑,趋化因子1(CXCL1)↑,巨噬细胞炎症蛋白-2(MIP-2)↑,一氧化氮(NO)↑,γ干扰素(IFN-γ)↓,环氧化酶-2(COX-2)↑,前列腺素E2(PGE2)↑,组胺↑,血栓素B2(TXB2)↑,6-酮-前列腺素F1α/TXB2↑,血管生成素-2(Ang-2)↑,骨桥蛋白(OPN)↑,调节激活正常T细胞表达分泌因子(RANTES)↑,髓过氧化物酶(MPO)↑,血管细胞间黏附分子1(VCAM-1)↑,内皮素-1(ET-1)↑,可溶性尿激酶型纤溶酶原激活物受体(suPAR)↑,磷脂酰肌醇-3激酶(PI3K)↑,丝苏氨酸激酶(AKT)↑,C反应蛋白(CRP)↑,超敏(hs)-CRP↑;核转录因子-κB(NF-κB)↑,IκB激酶α(IκKα)↑,IKβ激酶(IκKβ)↑,磷酸化NF-κB抑制蛋白α(p-IκBα)↑,NF-κB p50↑,NF-κB p65↑,磷酸化NF-κB-p65↑,c-Jun氨基末端激酶(JNK)↑,磷酸化JNK↑, p38丝裂原活化蛋白激酶(p38MAPK)↑,Smad2↑、Smad 3↑,Smad 7↓;Toll样受体(TLR)2↑,TLR4↑,髓样分化因子88(MyD88)↑,自噬效应蛋白1(Beclin-1)↑,微管相关蛋白轻链3Ⅱ(LC3-Ⅱ)↑,核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)↑,磷酸化酪氨酸激酶2(p-JAK2)↑,信号转导与转录激活因子1(STAT1)↑,磷酸化STAT3↑,细胞因子信号转导抑制因子1(SOCS1)↑,活化STAT蛋白质抑制因子3(PIAS3)↑;磷酸化AKT↑, 磷酸化κB抑制蛋白激酶α/β(p-IKKα/β)↑,磷脂酶Cβ(PLCβ)、磷脂酶C-γ1(PLC-γ1)和蛋白激酶C(PKC)↑,细胞外调节蛋白激酶(ERK)↑; (5)炎症、粘连等相关信号通路:①TLR4/髓样分化因子88(MyD88)/NF-κB信号通路中,TLR4↑、MyD88↑;②成纤维细胞生长因子(FGF)-2/激活FGF-2的受体1(FGFR1)信号通路中,PGE2↑、组胺↑,FGFR1↑,FGF-2↑;③NF-κB/TGF-β1/Smads信号通路中,NF-κB p65↑,TGF-β1↑,Smad 2↑,Smad 3↑,Smad7↓;④TLRs的信号转导途径之一PI3K/AKT信号通路中PI3K↑,AKT↑;⑤MAPK信号通路之JNK、p38信号通路中JNK↑,p38↑,p-JNK↑,p-p38↑;⑥JAK2/STAT3信号通路中,p-JAK2↑,p-STAT3↑,SOCS1↑,PIAS3↑;⑦JAK2/STAT1信号通路中,p-JAK2↑,p-STAT1↑,SOCS1↑,PIAS3↑;⑧ PLC/PKC信号通路中,PLC-β3↑,PLC-γ1和PKC的磷酸化↑;⑨ TLR4/NFκB/COX2信号通路中,TLR4↑,NF-κB↑,COX2↑[ |
氧化应激损伤Oxidative stress damage | 丙二醛↑,总抗氧化能力↓,超氧化物歧化酶↓,一氧化氮合酶(NOS)↑[ |
细胞凋亡 Apoptosis | 含半胱氨酸的天冬氨酸蛋白水解酶(caspase)-3↑,caspase-8↑,切割型caspase-3↑,切割型caspase-8↑,caspase-1↑;凋亡相关斑点样蛋白(ASC)↑,前B细胞克隆增强因子(PBEF)↑,Bcl-xl↑,Bcl-2关联的X蛋白(BAX)↑,B淋巴细胞瘤-2(BCL-2)↓,自杀相关因子↑,自杀相关因子配体(FasL)↑,肿瘤抑制基因(p53)↑,程序性死亡受体-1(PD-1)↓,程序性死亡受体配体-1(PD-L1)↓,TNF受体1(TNFR-1)↑,葡萄糖调节反应蛋白78(GRP78)↑,CCAAT增强子结合蛋白同源蛋白(CHOP)↑,TUNEL细胞凋亡率↑[ |
组织增生、粘连及纤维化 Tissue proliferation, adhesion,and fibrosis | 转化生长因子-β1↑,细胞间黏附分子-1↑,FGF2↑,胰岛素样生长因子-1(IGF-1)↑,Ⅰ型胶原蛋白↑,结缔组织生长因子↑,纤溶酶原激活剂抑制因子-1↑,组织型纤溶酶原激活剂(t PA)↓, 血管内皮生长因子(VEGF)↑,表皮生长因子(EGF)↓,黏蛋白-1(MUC-1)↓,基质血小板衍化生长因子(PDGF)↑,基质金属蛋白酶(MMP)2↑,MMP-9↑,金属蛋白酶抑制因子↑,磷酸化细胞外调节蛋白激酶(p-Erk1/2)↑,整合素αVβ3↓,同源框基因A10(HOXA10)↓,Ⅱ型TGF-β受体(TβRⅡ)↑[ |
免疫系统平衡失调 Imbalance of immune system | (1)免疫球蛋白:免疫球蛋白(Ig)A、IgG、IgM↓,分泌型IgA↓; (2)红细胞免疫指标检测:红细胞C3b受体花环率↓,红细胞免疫复合物花环率↑,细胞免疫黏附促进率(RFER)↓,红细胞免疫黏附抑制(RFIR)↑; (3)免疫细胞功能:CD4+CD25+调节性T细胞↑,CD4+↑,CD8+↓,自然杀伤性T细胞↓, CD3+↓,CD4+/CD8+↓, T细胞百分率、淋转率↓,自然杀伤(NK)细胞↓,调节性T细胞↓,辅助性T细胞17↑,辅助性T淋巴细胞(Th)、细胞毒性T淋巴细胞(Tc)、CD8细胞↑;巨噬细胞吞噬能力↓,血清总补体↓[ |
血液流变异常 Hemorheological abnormalities | 全血黏度低中高切↑,血浆黏度↑、红细胞聚集指数↑、全血高切相对指数↑、全血低切相对指数↑,还原黏度低中高切↑,红细胞压积↑,红细胞刚性指数↑、变形指数↑、电泳时间↑,全血卡松黏度和血小板聚集率↑,血沉和血沉方程K值↑[ |
肝肾功能障碍 Liver and kidney dysfunction | 促肾上腺皮质激素释放激素↑,促肾上腺皮质激素↑,肾上腺皮质酮↑,丙氨酸转氨酶↑,白蛋白↑,天冬氨酸转氨酶↑,碱性磷酸酶↑,肌酐↑,葡萄糖↑[ |
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