晚期糖尿病大鼠主动脉病理改变及环孢素A保护作用的研究  

Study on aortic pathological changes of rats with advanced diabetic mellitus and the protective effect of cyclosporine A

作　　者：叶东海 姜丽娟[2] 韩会民[2] 赵越 

机构地区：[1]大庆油田总院集团解放社区卫生服务中心,黑龙江大庆163461 [2]大庆市第四医院,黑龙江大庆163712 [3]大庆油田总院集团南区医院,黑龙江大庆163461

出　　处：《中国中西医结合急救杂志》2011年第3期170-173,共4页Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care

基　　金：黑龙江省自然科学基金项目（D200832）

摘　　要：目的探讨晚期糖尿病（DM）大鼠主动脉病理改变及环孢素A（CsA）的保护作用。方法将30只雄性Wistar大鼠按随机数字表法均分为正常对照组、模型组、CsA组3组。腹腔注射链脲佐菌素（STZ）方法制备大鼠DM模型，并使血糖维持在20-25mmol／L。CsA组于成模后28周给予CsA3mg·kg-1·d-1口服6周。成模34周后处死大鼠，取主动脉组织常规固定、脱水、包埋、切片，进行苏木素一伊红（HE）染色、Masson染色观察主动脉病理变化及间质纤维化程度；用免疫组化染色半定量分析IgG、IgA、核转录因子-κB（NF-κB）、转化生长因子-β1（TGF—β1）水平。结果模型组大鼠主动脉管壁可见淋巴细胞浸润，胶原纤维增生；CsA组较模型组有所减轻。免疫组化半定量分析显示，模型组、CsA组IgG、IgA、NF—κB及TGF—β1的积分吸光度（A）值（×10。）显著高于正常对照组（IgA：196．54±60．76、94．02±17．01比37．78±12．31；IgG：133．18±19．38、60．77±30．30比13．11±3．22；NF—κB：159．35±28．20、100．90±49．84比55．01±13．71；TGF-β1：175．46±26．40、132．33±42．63比37．78±16．60，P〈0．05或P〈0．01），且CsA组明显低于模型组（P〈0．05或P〈0．01）。随DM病程延长，免疫球蛋白及细胞因子沉积越多、主动脉病变越重。结论晚期DM主动脉存在病理损伤和功能异常，CsA可能通过减少主动脉免疫球蛋白沉积量和细胞因子表达起保护作用。Objective To study the aortic pathological changes of rats with advanced diabetic mellitus （DM） and the protective effect of cyclosporine A （CsA） on them. Methods Thirty male Wistar rats were randomly divided into three groups： normal control, model and CsA groups. The DM rat model was reproduced by intraperitoneal injection of streptozotocin （STZ）, and its blood glucose was maintained at 20 - 25 mmol/L. Twenty-eight weeks after modeling, CsA 3 mg· kg-1 · d-1 was given orally to the rats in CsA group for 6 weeks. Rats were sacrificed at 34 weeks after modeling, the aortic specimen was taken to make conventional fixation, dehydration, embedment and hematoxylin-eosin （HE） stain and Masson stain to observe the pathological changes and degree of aortic interstitial fibrosis; IgG, IgA, nuclear factor-κB （NF-κB） and transforming growth factor-β1 （TGF-β1） were observed by immunohistoehemical staining and semi-quantitative analysis. Results There were lymphocyte infiltration and collagen fiber hyperplasia in aortic wall of model group, and the aortic pathological changes were milder in CsA group. Semi-quantitative analyses of immunohistochemistry showed that the integral absorbance （A） values （X 103） of IgG, IgA, NF-κB and TGF-β1 in model group and CsA group were significantly higher than those in normal control group （IgA： 196.54±60.76, 94.02±17.01 vs. 37.78±12.31; IgG： 133.18±19.38, 60.77±30.30 vs. 13.11±3.22; NF-κB：159.35±28.20, 100.90±49.84 vs. 55.01±13.71; TGF-β1：175.46±26.40, 132.33±42.63 vs. 37.78±16.60, P〈0.05 or P〈0. 01）, and those in the CsA group was obviously lower than those in model group （P〈0. 05 or P〈0. 01）. Along with the prolongation of DM course, the immunoglobulin deposition and cytokine expression became more and more in quantity, and the aortic pathological changes revealed severer. Conclusion There are pathological damage and dysfunction of the aorta in the advanced DM rat, and CsA may play a protective role by reducing

关 键 词：糖尿病 主动脉 环孢素A 免疫球蛋白 转化生长因子-Β1 核转录因子-ΚB 

分 类 号：R587.1[医药卫生—内分泌] R361.2[医药卫生—内科学]