氯沙坦对糖尿病大鼠胰岛组织中转化生长因子-β_1 Smad7蛋白表达的影响  

Effects of Losartan on expression of transforming growth factor-β_1 and Smad7 in pancreatic tissues of diabetic rats

作　　者：吴慧璐[1] 何军华[1] 王丽[1] 程瑞[1] 范运娟 

机构地区：[1]山西医科大学第二医院内分泌科,太原030001

出　　处：《中国药物与临床》2014年第3期284-286,共3页Chinese Remedies & Clinics

基　　金：山西省自然科学基金(2009011056-2);山西省卫生厅科研项目(201201074)

摘　　要：目的探讨血管紧张素Ⅱ(AngⅡ)受体阻滞剂氯沙坦对糖尿病大鼠胰岛组织中转化生长因子(TGF)-β1、Smad7表达的影响,从而验证氯沙坦在糖尿病大鼠胰腺组织纤维化中的作用。方法以健康成年Wistar大鼠为实验对象,随机分为正常组、糖尿病对照组和糖尿病氯沙坦干预组3组。正常组以普通饲料喂养,糖尿病对照组和糖尿病氯沙坦干预组以高脂高热量饲料喂养。8周后予糖尿病对照组和糖尿病氯沙坦干预组腹腔注射链脲佐菌素(STZ)诱导糖尿病大鼠模型,造模成功后,对糖尿病氯沙坦干预组大鼠给予氯沙坦30 mg·kg-1·d-1灌胃治疗,8周后检测各组大鼠的体质量、血糖、血胰岛素,然后处死取出胰腺组织,采用免疫组织化学方法检测胰岛组织中TGF-β1、Smad7蛋白的表达,用彩色病理图像分析系统进行定量分析。结果糖尿病对照组较正常对照组血糖增高,血胰岛素水平降低,并有明显的体质量减轻;胰岛组织中的TGF-β1蛋白含量增加,Smad7蛋白含量减少。氯沙坦干预组较糖尿病对照组各项指标均有明显改善,差异有统计学意义(P<0.05)。结论 AngⅡ受体阻滞剂氯沙坦对糖尿病大鼠胰岛组织纤维化有一定抑制作用,其作用机制可能与调节TGF-β1/Smads信号转导通路有关。Objective To investigate the effects of Losartan, the antagonist of angiotensin Ⅱ receptor, on ex- pression of transforming growth factor-β1 （TGF-β1） and Smad7 in pancreatic tissue of diabetic rats, which may help confirm the effect of Losartan on pancreatic tissue fibrosis in diabetic rats. Methods Healthy male adult Wistar rats were randomly assigned to be fed with normal diet （normal control group）, high-fat and -sugar diet （diabetic rat group） and high-fat and -sugar diet plus Losartan （Losartan-intervention group）. At week 8 diabetic rats group and Losartan- intervened group were subject to streptozotocin injection to induce the construction diabetic rat models. This was fol- lowed by gastric administration of Losartan 30 mg·kg^-1· d^-1 in the Losartan-intervention group. This has allowed the measurement of serum glucose, insulin and weight at week 8. The rats were sacrificed to extract pancreatic tissues. The levels of TGF-β1 and Smad7 protein in pancreatic tissues were examined by immunohistochemistry and quantita- tively analyzed by color pathological image analysis system. Results Compared with normal control group, the level of serum glucose was markedly higher and insulin and decreased in the diabetic rat group, which was evidenced by the significantly increased levels of TGF-β1 and Smad7 in pancreatic tissues. Losartan resulted in remarkable improve- ment in all indices （all P〈0.05）. Conclusion The inhibitory effects of Losartan, the antagonist of angiotensin Ⅱ re- ceptor, on pancreatic tissue fibrosis in diabetic rats may be related to regulation of TGF-β1/Smads signaling pathways.

关 键 词：糖尿病 2型 转化生长因子Β SMAD7 胰岛 纤维化 

分 类 号：R587.1[医药卫生—内分泌]