[关键词]
[摘要]
目的 采用数据挖掘方法总结肺纤维化动物模型的特点及建立药效指标评价体系。方法 通过中国知网 (CNKI)、万方数据库(Wangfang)、维普中文科技期刊全文数据库(VIP)、PubMed、Web of Science、Embase 数 据库检索与肺纤维化动物药效研究相关的文献,归纳整理、分析肺纤维化动物模型的造模方法、干预药物等, 并统计检测指标类型、方法等,构建肺纤维化动物药效指标体系。结果 共纳入 1 174 篇文献,动物造模常见 的诱导因素有肿瘤药物、环境/职业暴露颗粒、物理因素等,以 C57 BL/6 小鼠、SD 大鼠为主要研究对象,其 中博来霉素以无创性气管滴注诱导肺纤维化动物模型最常见。肺纤维化动物药效研究中常见的干预药物有化学 药、抑制剂/激动剂、天然药物、中药复方等。肺纤维化动物药效研究中检测指标包括一般情况、肺功能、肺 组织病理、细胞外基质、上皮间质转化、细胞因子、氧化应激等七类,其中一般情况以体质量、肺系数、生存 分析检测为主;肺功能指标主要包括用力肺活量、动态肺顺应性、潮气量等;常见的肺组织病理染色方法有 HE 染色、Masson 染色及天狼猩红染色等;细胞外基质检测指标以Ⅰ型胶原蛋白、羟脯氨酸、纤维连接蛋白等 为主;上皮间质转化指标有 α-平滑肌肌动蛋白、E-钙黏蛋白、波形蛋白等;细胞因子检测指标主要有转化生 长因子 β1、肿瘤坏死因子 α、白细胞介素 6 等;氧化应激检测指标主要包括丙二醛、超氧化物歧化酶、谷胱 甘肽等。根据检测指标频次≥200 次作为肺纤维化动物药效研究检测的强推荐指标,将一般情况(体质量、肺系 数)、肺病理(HE 染色、Masson 染色等)、细胞外基质(羟脯氨酸、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白、纤维连接蛋 白)、上皮间质化(α-平滑肌肌动蛋白)、细胞因子(肿瘤坏死因子 α、白细胞介素 6/1β、转化生长因子 β1)作为 肺纤维化动物药效研究检测的强推荐指标。结论 本研究为肺纤维化动物模型构建及药效指标评价体系的建立 提供了更多参考。
[Key word]
[Abstract]
Objective To summarize the characteristics of animal models of pulmonary fibrosis and establish an efficacy indicator evaluation system using data mining methods. Method Literature related to pharmacological studies of pulmonary fibrosis in animals was retrieved from databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, Web of Science, and Embase. The modeling methods, intervention drugs, and other aspects of animal models of pulmonary fibrosis were summarized and analyzed. The types and methods of detection indicators were statistically analyzed to form an efficacy indicator system for animal studies of pulmonary fibrosis. Results A total of 1 174 articles were included. Common inducing factors for animal modeling included antineoplastic drugs,environmental/occupational exposure particles,and physical factors. C57 BL/6 mice and SD rats were the main research subjects. Among these,bleomycin-induced pulmonary fibrosis models via non-invasive tracheal drip were the most common. Common intervention drugs in animal efficacy studies of pulmonary fibrosis included chemical drugs, inhibitors/agonists, natural products, and traditional Chinese medicine compounds. Detection indicators in animal efficacy studies of pulmonary fibrosis were categorized into seven types: general condition, pulmonary function, histopathology, extracellular matrix, epithelial-mesenchymal transition (EMT), cytokines, and oxidative stress. General condition indicators primarily included body weight, lung coefficient, and survival analysis. Pulmonary function indicators mainly included forced vital capacity,dynamic lung compliance,and tidal volume. Common lung histopathological staining methods included hematoxylin-eosin (HE) staining, Masson staining, and Sirius red staining. Extracellular matrix detection indicators mainly included type Ⅰ collagen,hydroxyproline,and fibronectin. EMT indicators included α-smooth muscle actin (α-SMA),E-cadherin,and vimentin. Cytokine detection indicators mainly included transforming growth factor- β1(TGF-β1),tumor necrosis factor- α(TNF-α),and interleukin-6 (IL-6). Oxidative stress detection indicators mainly included malondialdehyde (MDA),superoxide dismutase (SOD), and glutathione (GSH). Based on detection indicators with a frequency≥200 times,strongly recommended indicators for animal efficacy studies of pulmonary fibrosis were identified as:general condition (body mass,lung coefficient),lung pathology (HE staining, Masson staining, etc.), extracellular matrix (hydroxyproline, type Ⅰ and Ⅲ collagen, fibronectin),EMT (α-SMA),and cytokines (TNF-α,IL-6/IL-1β,TGF-β1). Conclusion This study provides additional references for the construction of animal models of pulmonary fibrosis and the establishment of an efficacy indicator evaluation system.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金区域联合重点项目(U23A20503);河南省科技研发计划联合基金(优势学科培育类)重点项目(232301420020)。