硫化氢通过调控转化生长因子-β及基质金属蛋白酶-9/基质金属蛋白酶抑制剂-1改善糖尿病大鼠肾小管间质纤维化  

Hydrogen sulfide alleviates renal fibrosis in diabetic rats through TGF-β,MMP-9 and TIMP-1 signaling pathway

作　　者：李子宁[1] 梁彪[1] 刘茂军[1] 褚春[2] 曾欧[1] 李琳[1] 李妍[1] 杨军[1] LI Zi-Ning LIANG Biao LIU Mao-Jun et al(Department of Cardiology, the First Affiliated Hospital of South China University, Hengyang 421001, Hunan, China)

机构地区：[1]南华大学附属第一医院老年医学科,湖南衡阳421001 [2]南华大学附属第二医院药剂科

出　　处：《中国老年学杂志》2017年第3期544-546,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金(No.81270181)

摘　　要：目的探讨硫化氢(H_2S)气体信号分子对糖尿病大鼠肾小管间质纤维化及转化生长因子(TGF)-β、基质金属蛋白酶(MMP)-9/基质金属蛋白酶抑制剂(TIMP)-1表达的影响。方法单次腹腔注射链脲佐菌素(STZ)建立糖尿病模型将成年雄性SD大鼠64只随机分为正常对照组(Control组)、STZ组、STZ+H_2S组、H_2S组。造模72 h后采尾静脉血检测,若血糖>16.7 mmol/L表明造模成功。H_2S组和STZ+H_2S组大鼠腹腔注射Na HS溶液100μmol·kg^(-1)·d^(-1),Control组和STZ组腹腔注射同等量生理盐水。8 w后取标本,Masson染色观察大鼠肾脏组织病理形态学改变,Western印迹检测大鼠肾脏TGF-β、MMP-9、TIMP-1、Ⅳ型胶原蛋白的表达水平。结果与Control组相比,STZ组存在明显肾小管间质纤维化,同时肾脏组织中Ⅳ型胶原、TGF-β、TIMP-1蛋白的表达升高,MMP-9蛋白的表达水平下降(P<0.05);与STZ组大鼠相比,STZ+H_2S组肾小管间质纤维化减轻,肾组织TGF-β、TIMP-1、Ⅳ型胶原蛋白的表达降低,MMP-9蛋白表达水平升高(P<0.05)。结论 H_2S可改善糖尿病大鼠肾小管间质纤维化,其机制可能与调控MMP-9/TIMP-1失衡以及TGF-β蛋白的表达水平有关。Objective To explore the effects of hydrogen sulfide on glomerular fibrosis in diabetic rats and the expressions of TGF-β, MMP-9 and TIMP-1. Methods 64 adult male SD rats were randomly divided into control, streptozotocin（ STZ）, diabetic rats with H2S treatment （STZ＋H2S） and normal rats with H2S treatment （H2S） groups. Diabetes mellitus was induced by the intraperitoneal injection of STZ. After the model was established successfully, the rats in STZ＋H2S and H2S groups were given daily intraperitoneal injections of NaSH （100 μmol/kg） ,while the rats in control and STZ groups were given saline. After 8 weeks, the pathologies of renal interstitial fibrosis were examined by Massion staining, and the expressions of CollagenlV, TGF-β, MMP-9 and MMP-1 were analyzed by Western blot. Results Compared with those of control group, the rats in STZ group showed obvious glomerular fibrosis in the nephridial tissue with significantly in- creased expression levels of Collagen lV, TGF-β and TIMP1 and decreased expression level of MMP9 （P〈0.05）, while changes in STZ＋H2S group were significantly reversed （P〈0.05）. Conclusions Hydrogen sulfide could alleviate glomerular fibrosis in diabetic rats, and the mechanism might involve the regulation of MMP-9/TIMP-1 imbalance and the level of TGF-β protein expression.

关 键 词：硫化氢 糖尿病 转化生长因子-Β 基质金属蛋白酶抑制剂-1 基质金属蛋白酶-9 

分 类 号：R587.1[医药卫生—内分泌]