实验性自身免疫葡萄膜炎大鼠模型炎症程度影响因素及中西医病证特点分析

Influencing Factors on Degree of Inflammation in Experimental Autoimmune Uveitis Rat Model and Characteristics of Traditional Chinese and Western Medicine Symptoms

摘要:

目的 探讨不同的乳化混合物及乳化方法对实验性自身免疫性葡萄膜炎（EAU）大鼠模型炎症程度的影响及当下EAU模型特点分析。方法 通过给路易斯（Lewis）大鼠皮下注射弗氏完全佐剂（CFA）乳化的光感受器间视黄醇结合蛋白（IRBP ）1177-1191皮下免疫，同时予以腹腔注射或不注射百日咳毒素（PTX），建立EAU模型。使用裂隙灯、苏木素-伊红（HE）染色、眼底光学相干断层扫描对EAU造模相关影响因素进行了评估，包括乳化混合物（IRBP1177-1191、PTX、灭活的结核分枝杆菌）的不同剂量及4种不同乳化方法。通过慢性葡萄膜炎的中西医临床诊断标准及病证特点，对EAU动物模型的分类、特点、造模方法、优缺点及中西医病证的吻合度进行归纳与分析。结果 就乳化混合物的乳化剂量而言，增加灭活的结核分枝杆菌、抗原肽的剂量可以加重EAU大鼠眼前节炎症反应。增加注射PTX可以加重EAU大鼠眼前节炎症反应及视网膜厚度。就乳化方法而言，EAU模型的严重程度与乳化方法密切相关。4种乳化方法均可以成功诱导大鼠EAU。相比较而言，超声波细胞粉碎机和T10基本型分散机可以在短时间内获得乳化成功的乳液。乳化混合物的乳化程度也影响EAU大鼠模型严重程度。现有的EAU动物模型与西医诊断及中医眼部主证吻合度较高。结论 IRBP1177-1191、PTX、灭活的结核分枝杆菌、乳化方法可通过不同的途径影响EAU模型的严重程度。现有的EAU动物模型可以较好地模拟西医临床特点，但欠缺中医病因病机及证候特点。因而有必要构建病证结合的EAU动物模型。

Abstract:

Objective To explore the effects of different emulsion mixtures and emulsification methods on the inflammation severity in an experimental autoimmune uveitis （EAU） model in rats， and to analyze the characteristics of the current EAU model.Method EAU was induced in Lewis rats by subcutaneous injection of interphotoreceptor retinoid-binding protein （IRBP） 1177-1191 emulsified with Freund's complete adjuvant （CFA）， with or without intraperitoneal injection of pertussis toxin （PTX）. Slit lamp examination， HE staining， and optical coherence tomography were used to evaluate factors affecting EAU modeling， including different doses of the emulsion mixture （IRBP1177-1191， PTX， and inactivated Mycobacterium tuberculosis） and four different emulsification methods. The classification， characteristics， modeling methods， advantages， and disadvantages of EAU animal models were summarized and analyzed based on the clinical diagnostic criteria and syndrome characteristics of chronic uveitis in both traditional Chinese medicine （TCM） and western medicine， to evaluate the consistency between TCM and western medical syndromes.Result Increasing the dose of inactivated M. tuberculosis and antigen peptide in the emulsion mixture exacerbated the anterior segment inflammation in EAU rats. Increasing the injection of PTX also exacerbated anterior segment inflammation and increased retinal thickness in EAU rats. The severity of the EAU model was closely related to the emulsification method used. All four emulsification methods successfully induced EAU in rats. Comparatively， the ultrasonic cell disruptor and T10 basic disperser achieved successful emulsification in a short time. The degree of emulsification of the mixture also influenced the severity of the EAU model in rats. The existing EAU animal model shows a high degree of consistency with western medical diagnoses and the main ocular syndromes in TCM.Conclusion IRBP1177-1191， PTX， inactivated M. tuberculosis， and emulsification methods can affect the severity of the EAU model through different pathways. The existing EAU animal models can simulate the clinical characteristics of western medicine well but lack the etiology， pathogenesis， and syndrome characteristics of TCM. Therefore， it is necessary to construct an EAU animal model that combines disease and syndrome characteristics.