硫化氢对大鼠糖尿病心肌病心肌间质纤维化及JAK2/STAT3通路的影响  

The influence of hydrogen sulfide on myocardial interstitial fibrosis and JAK2/STAT3signal pathway in rats diabetic cardiomyopathy

作　　者：杨萍 庞金伟 刘星 吴鹏 范忠才 YANG Ping PANG Jinwei LIU Xing WU Peng FAN Zhongcai(The Southwest Medical University, Luzhou, Sichuan, 646000, China The Affiliated Hospital of The Southwest Medical University)

机构地区：[1]西南医科大学,四川泸州646000 [2]西南医科大学附属医院心内科

出　　处：《临床心血管病杂志》2016年第12期1258-1262,共5页Journal of Clinical Cardiology

基　　金：四川省科学技术厅-泸州市人民政府-泸州医学院联合科研专项资金(No:0903-100020802)

摘　　要：目的:观察硫化氢(H_2S)对糖尿病心肌病(DCM)大鼠心肌组织纤维化、JAK2/STAT3通路及炎性因子表达的影响,探讨H_2S对DCM的作用及其机制。方法:运用糖尿病饮食联合链脲佐菌素(STZ)腹腔注射法建立SD大鼠2型糖尿病模型,选取随机血糖>16.7 mmol/L的大鼠20只随机分成DCM+0.9%氯化钠组(DCM+saline)、DCM+硫化氢组(DCM+NaHS),每组10只。另选20只正常大鼠随机分成正常对照组(Con trol+saline)、正常对照+硫化氢组(Control+NaHs),每组10只。从造模成功后第8周起,DCM+NaHS组和Control+NaHS组大鼠腹腔注射NaHS溶液100μmol·kg^(-1)·d^(-1),Control+saline组和DCM+saline组腹腔注射等量0.9%氯化钠。第12周未处死大鼠,取左心室心肌组织提取蛋白和制作常规石蜡切片。运用Masson染色观察大鼠心肌间质纤维化并计算心肌间质胶原容积分数(CVF);运用Western blot技术检测大鼠心肌组织Ⅰ型、Ⅲ型胶原;磷酸化JAK2(p-JAK2)、磷酸化STAT3(p-STAT3)蛋白表达水平;运用酶联免疫吸附试验(ELISA)方法检测炎性因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)表达水平。结果:与Control+Saline组相比,DCM+Saline组大鼠CVF明显增加,同时心肌组织中Ⅰ型、Ⅲ型胶原蛋白表达水平明显升高,pJAK2、p-STAT3蛋白的表达水平明显升高,IL-1β、IL-6、TNF-α的表达水平也明显升高(均P<0.05)。与DCM+Saline组相比,DCM+NAHS组大鼠CVF明显降低,心肌组织Ⅰ型、Ⅲ型胶原蛋白、p-JAK2、p-STAT3和IL-1β、IL-6、TNF-α的表达水平明显降低(均P<0.05)。与Control+Saline组相比,Control+NaHS组各检测指标无明显差异。结论:H_2S对正常大鼠心肌间质纤维化无明显影响,但给予外源性H_2S干预可改善DCM大鼠心肌间质纤维化程度,其机制可能与下调JAK2/STAT3通路的活化有关。Objective：To investigate the effects of exogenous hydrogen sulfice（H2S） administration on the myocardial interstitial fibrosis,the activation of JAK2/STAT3 pathway and the release of inflammatory cytokines in experimental diabetic cardiomyopathy（DCM） in rats.Method：DCM models were established using streptozocin intraperitoneal injection combing with diabetic diets in young male adult Sprague-Dawley rats.NaHS was used as the donor of exogenous H2S.20 male type 2 diabetic rats with blood glucose higher than 16.7 mmol/L were randomly designed into DCM ＋ Saline and DCM ＋ NaHS group（n= 10）.Another 20 male rats were randomly designed into Control＋Saline and Control ＋ NaHS group（n =10）,8 weeks after the establishment of type 2 diabetes,rats in Control ＋ NaHS and DCM＋NaHS groups were injected with NaHS 100 μmol·kg^-1·d^-1 intraperitoneally.Rats in Control＋Saline and DCM＋Saline groups were recieved equal saline instead.All rats were sacrificed 12 weeks after the establishment of type 2 diabetes.The left heart ventricular tissues of rats were harvested.Western blotting was used to measure the expression of p-JAK2 and p-STAT3.Enzyme-1 linked immunosorbent assay（EL1SA） was used to quantify the release of 1L-1β,1L-6 and TNF-α.Collagen volume fraction（CVF） in masson staining was calculated to explore the extent of myocardial interstitial fibrosis.Results：Compared with the Control ＋ Saline group,the CVF,expressions of type Ⅰ and type Ⅲ collagen in DCM ＋ Saline group were dramatically increased,indicating that the myocardial interstitial fibrosis was significantly higher in DCM rats.Meanwhile,the release of inflammatory cytokines including 1L-1β,IL-6 and TNF-α,the expressions of p-JAK2 and p-STAT3 were also significantly upregulated in DCM rats.Fortunately,after the administration of NaHS,the CVF in DCM＋ NaHS group rats was dramatically decreased while the expressions of type Ⅰ and type Ⅲ collagen were also significantly downregulated.Moreover,the release of infl

关 键 词：糖尿病心肌病 心肌间质纤维化 硫化氢 JAK2/STAT3 炎症 

分 类 号：R542.2[医药卫生—心血管疾病]