基于数据挖掘的盆腔炎性疾病动物模型应用分析

doi:10.12300/j.issn.1674-5817.2024.012

实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (4): 405-418.DOI: 10.12300/j.issn.1674-5817.2024.012

基于数据挖掘的盆腔炎性疾病动物模型应用分析

郑艺清, 邓亚胜, 范燕萍, 梁天薇, 黄慧, 刘永辉, 倪召兵, 林江()()

广西中医药大学基础医学院, 南宁 530200

收稿日期:2024-01-22 修回日期:2024-04-07 出版日期:2024-09-06 发布日期:2024-08-25
通讯作者: 林江（1963—），女，博士，教授，博士生导师，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:郑艺清（1998—），女，硕士研究生，研究方向：特色方剂的配伍及成药化研究。E-mail: 13063001367@163.com
基金资助:
全国高校黄大年式教师团队——广西中医药大学中西医基础课程教师团队(教育部教师函〔2022〕2号);广西名中医林江传承工作室(桂中医药科教发〔2021〕6号);广西一流学科建设项目——广西中医药大学中医学(桂教科研〔2022〕1号);广西中医药多学科交叉创新团队项目“中医药活性传承的广西海洋健康产业产品与装备创新团队”(GZKJ2302)

Application Analysis of Animal Models for Pelvic Inflammatory Disease Based on Data Mining

ZHENG Yiqing, DENG Yasheng, FAN Yanping, LIANG Tianwei, HUANG Hui, LIU Yonghui, NI Zhaobing, LIN Jiang()()

School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning 530200, China

Received:2024-01-22 Revised:2024-04-07 Published:2024-08-25 Online:2024-09-06
Contact: LIN Jiang (ORCID: 0009-0009-6182-2335), E-mail: 1713552545@qq.com

摘要/Abstract

摘要：

目的探究盆腔炎性疾病（pelvic inflammatory disease，PID）动物模型的造模要素和评价指标，为改进PID动物模型的造模方法、完善PID动物模型的合理应用提供参考依据。方法以“盆腔炎”并且“动物模型”或“鼠”或“豚鼠”或“兔”或“犬”或“猪”为主题词，在中国知网数据库、万方数据库和PubMed中检索2013—2023年发表的PID动物模型相关文献，对文献中记载的实验动物种类、造模方法、造模周期、检测指标、阳性对照用药和给药时间等内容进行整理归纳，建立数据库并进行统计分析。结果检索筛选出214篇符合纳入标准的PID动物模型文献。其中，模型动物种类选用最多的是SD大鼠，其次为Wistar大鼠；最常用的造模方式是机械损伤联合细菌感染法，其次是苯酚胶浆法；急性盆腔炎（acute pelvic inflammatory disease，APID）和慢性盆腔炎（chronic pelvic inflammatory disease，CPID）/盆腔炎性疾病后遗症（sequelae of pelvic inflammatory disease，SPID）动物造模周期频次最高的是8～14 d，其他不明确分期PID造模周期频数最高的是7 d；高频检测指标包括用苏木精-伊红染色法观察组织病理、酶联免疫吸附法检测血清相关指标、肉眼观察组织外观变化、免疫组化法检测子宫组织中相关蛋白表达和病理评分等；阳性对照药物应用频次最高的是妇科千金片，其次是金刚藤胶囊；APID给药时间频数最高的是7 d，CPID/SPID动物模型给药时间频次最多的是15～21 d。结论目前SD大鼠和Wistar大鼠是制备PID模型常用的实验动物，采用机械损伤加混合细菌感染双重造模法与临床发病机制吻合度较高，可建立术后宫腔感染引起的PID模型；根据研究目的不同，可选取不同的阳性对照药物和检测指标进行整体评价。现有的PID动物模型研究大都以西医诊断为标准，对中医症候动物模型的研究较少，需结合中医理论病因病机，构建更符合中医临床病证的PID动物模型。

关键词: 数据挖掘, 盆腔炎性疾病, 动物模型, 应用分析, 大鼠

Abstract:

Objective To investigate the key elements for model establishment and determine the evaluation indicators of animal models for pelvic inflammatory disease (PID), providing a reference for improving modelling methods and optimizing the application of PID animal models. Methods The search query "Pelvic Inflammatory Disease" AND "Animal Model" OR "Rat" OR "Mouse" OR" Guinea Pig" OR "Rabbit" OR "Dog" OR "Pig" was used to retrieve relevant literature on PID animal models published from 2013 to 2023 in China Knowledge Network Infrastructure (CNKI), Wanfang, and PubMed databases. The studies were analyzed and categorized based on experimental animal types, modelling methods, modelling cycles, detection indicators, positive control drugs, and administration duration. A database was established for statistical analysis. Results A total of 214 research articles on PID animal models meeting the inclusion criteria were identified. The most commonly used model animals are Sprague Dawley (SD) rats, followed by Wistar rats. The most frequently employed modelling method is a combination of mechanical injury and bacterial infection, followed by the phenol mucilage method. The most common modelling cycles for acute pelvic inflammatory disease (APID) and chronic pelvic inflammatory disease (CPID)/sequelae of pelvic inflammatory disease (SPID) are 8 to 14 days, while for PID models without specific staging, the cycles are 7 days. High-frequency detection methods and indicators include histopathological observation using hematoxylin-eosin staining, enzyme-linked immunosorbent assay (ELISA) for serum-related indicators, morphological changes of tissues observed with the naked eye, and immunohistochemical detection of related protein expression in uterine tissues, and pathological scoring. The most frequently used positive control drugs are Fuke Qianjin Tablets, followed by Jingangteng Capsules. The most common administration duration for APID is 7 days, and for CPID/SPID models, it ranges from 15 to 21 days. Conclusion Currently, SD rats and Wistar rats are commonly used as experimental animals for PID models. The dual modelling method of mechanical injury combined with mixed bacterial infection aligns closely with clinical pathogenesis and can be used to establish a PID model that simulates postoperative uterine cavity infection. Depending on the research objectives, different positive drugs and detection indicators should be selected for comprehensive evaluation. Most existing PID animal model studies are based on western medical diagnosis, with fewer studies focusing on Traditional Chinese Medicine (TCM) syndromes. There is a need to integrate TCM theories of etiology and pathogenesis to construct PID animal models that are more in line with TCM clinical symptoms.

Key words: Data mining, Pelvic inflammatory disease, Animal models, Application analysis, Rats

中图分类号:

R-332

郑艺清,邓亚胜,范燕萍,等. 基于数据挖掘的盆腔炎性疾病动物模型应用分析[J]. 实验动物与比较医学, 2024, 44(4): 405-418. DOI: 10.12300/j.issn.1674-5817.2024.012.

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.

图/表 6

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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)
化学因素造模 Chemical factor modelling	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)
生物因素造模 Biological factor modelling	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)

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)
化学因素造模 Chemical factor modelling	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)
生物因素造模 Biological factor modelling	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）

基于数据挖掘的盆腔炎性疾病动物模型应用分析

Application Analysis of Animal Models for Pelvic Inflammatory Disease Based on Data Mining

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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）

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