替米沙坦通过降低Chemerin表达减轻2型糖尿病小鼠肾脏炎症反应  

Telmisartan ameliorates renal inflammation in T2DM mice by reducing Chemerin expression

作　　者：施子禄[1] 郑丹丹 黄秋虹 张素萍 黄倩 SHI Zi-lu;ZHENG Dan-dan;HUANG Qiu-hong;ZHANG Su-ping;HUANG Qian(Dept of Nephrology,First Hospital of Quanzhou Affiliated to Fujian Medical College,Quanzhou,Fujian 362000,China;Dept of Physiology,Quanzhou Medical College,Quanzhou,Fujian 362100,China;Dept of Physiology,Zhejiang University School of Basic Medicine,Hangzhou 310058,China)

机构地区：[1]福建医科大学附属泉州第一医院肾内科,福建泉州362000 [2]泉州医学高等专科学校基础医学部生理学教研室,福建泉州362100 [3]浙江大学基础医学院生理系,浙江杭州310058

出　　处：《中国药理学通报》2018年第12期1725-1730,共6页Chinese Pharmacological Bulletin

基　　金：泉州市科技计划项目(No 2018Z179;2018Z167);泉州医学高等专科学校校级青年课题(No XJK1619B)

摘　　要：目的研究血管紧张素II受体1拮抗剂替米沙坦对2型糖尿病(T2DM)模型小鼠肾脏炎症反应的影响,并探讨其作用机制。方法高脂饮食饲养4周联合链脲佐菌素STZ(40 mg·kg^(-1))一次性腹腔注射构建T2DM小鼠模型,并随机分为T2DM组、替米沙坦(1、3 mg·kg^(-1))组、正常对照组,连续灌胃给药8周。检测各组小鼠空腹血糖(FBG)、24 h尿微量白蛋白(mAlb)、血清肌酐(Scr)和尿素氮(BUN)含量变化;HE染色观察肾脏病理学变化;酶联免疫吸附法(ELISA)检测肾皮质中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平;ELISA法检测肾皮质血管紧张素II(Ang II)浓度;免疫组织化学法观察肾皮质中Chemerin分布;Western blot检测肾皮质中Chemerin蛋白的表达。结果替米沙坦以血糖非依赖性方式,降低T2DM小鼠mAlb、Scr、BUN含量,并通过抑制肾脏Ang II的生成和Chemerin蛋白的分布、表达,减轻肾脏炎症反应。结论替米沙坦抑制了T2DM小鼠肾脏炎症反应,其机制可能与抑制肾脏局部肾素-血管紧张素系统及Chemerin蛋白的分布、表达有关。Aim To investigate the protective effects of telmisartan against renal inflammation in type 2 diabetes mellitus（T2DM） mouse model and explore the underlying mechanisms. Methods T2DM mouse model was induced by 4 weeks’ high fat diet feeding and one time streptozotocin （STZ） 40 mg·kg^-1 intraperitoneal injection and were randomly divided into the following four groups： T2DM group, telmisartan（1, 3 mg·kg^-1 ） group and normal control group. Eight weeks later, the level of fasting blood-glucose（FBG）, microalbuminuria（mAlb）, serum creatinine（Scr） and blood urea nitrogen（BUN） were detected. The pathological changes in kidney were assessed by HE staining. Interleukin-1β（IL-1β）, interleukin-6（IL-6）, tumor necrosis factor α（TNF-α） levels and angiotensin II（Ang II） concentration in renal cortex were detected by enzyme linked immunosorbent assay（ELISA）. The Chemerin protein distribution and expression in renal cortex were identified by immunohistochemical staining and Western blot, respectively. Results Telmisartan could markedly reduce the contents of mAlb, Scr and BUN in T2DM mice, improve the kidney architecture, meanwhile decrease the levels of IL-1β, IL-6 and TNF-α by inhibiting Ang II and Chemerin protein expression in renal cortex, leading to the alleviation of degree of renal inflammation in T2DM mice. Conclusions Telmisartan attenuates renal inflammation in T2DM mice model, and this effect might be associated with the suppression of renal local RAS and Chemerin protein expression.

关 键 词：替米沙坦 2型糖尿病 CHEMERIN 白细胞介素6 肿瘤坏死因子Α 炎症 

分 类 号：R-332[医药卫生] R322.61