外源性硫化氢对2型糖尿病大鼠心肌纤维化及TGF-β1/Smads信号通路的影响  

Effects of exogenous hydrogen sulfide on myocardial fibrosis and TGF-β1/Smads signaling pathway in type 2 diabetic rats

作　　者：曾奇虎 翁静飞 李小林 杨萍 白雪 范忠才(指导) ZENG Qi-Hu;WENG Jing-Fei;LI Xiao-Lin;YANG Ping;BAI Xue;FAN Zhong-Cai(The Affiliated Hospital of Traditional Chinese Medicine,Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属中医医院,泸州646000 [2]西南医科大学附属医院,泸州646000

出　　处：《中国免疫学杂志》2020年第6期653-657,共5页Chinese Journal of Immunology

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资助项目(No.0903-100020802)。

摘　　要：目的:观察外源性硫化氢(H2S)对2型糖尿病(T2DM)大鼠心肌间质纤维化和TGF-β1/Smads信号通路的影响,探究H2S对2型糖尿病大鼠心肌纤维化的作用及机制。方法:给予47只雄性SD大鼠高糖高脂饮食饲养4周并腹腔注射40 mg/kg链尿佐菌素(STZ)构建T2DM模型。腹腔注射后3 d和5 d采尾静脉血测血糖,血糖≥16.7 mmol/L提示糖尿病大鼠模型构建成功。选取糖尿病大鼠20只,正常大鼠20只,随机分组为:正常对照组(Control组)、硫氢化钠对照组(NaHS组)、糖尿病组(DM组)、糖尿病+硫氢化钠组(DM+NaHS组),每组10只。予以DM+NaHS组和NaHS组大鼠腹腔注射NaHS溶液100μmol/(kg·d),予以Control组和DM组腹腔注射等量生理盐水,持续12周。12周后,留取大鼠血清,检测空腹血糖(FBG);应用超声心动图测量各组大鼠左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室短轴缩短率(LVFS)、左心室射血分数(LVEF)和E/A ratio;采用Masson染色法评估心肌间质纤维化程度和使用Image-Pro Plus 6.0软件测定心肌间质胶原容积分数(CVF);应用Western blot检测心肌TGF-β1、Smad7、p-Smad2/3蛋白和Ⅰ型胶原蛋白表达水平。结果:与Control组相比,DM组大鼠FBG明显升高,心脏收缩与舒张功能恶化,心肌间质胶原纤维显著增加,CVF明显增加,TGF-β1、p-Smad2/3和心肌Ⅰ型胶原蛋白表达水平明显上调,Smad7蛋白明显下调(P<0.05);与DM组相比,DM+NaHS组大鼠血糖水平明显降低,心脏收缩与舒张功能改善,心肌间质胶原纤维明显减少,CVF明显减少,心肌组织TGF-β1、p-Smad2/3、心肌Ⅰ型胶原蛋白表达明显下调,Smad7蛋白明显上调(均P<0.05)。结论:外源性H2S对2型糖尿病大鼠心脏具有保护作用,其机制可能是与通过调控TGF-β1/Smads信号通路、改善糖尿病大鼠心肌纤维化有关。Objective:To observe the effects of exogenous hydrogen sulfide on cardiac fibrosis and TGF-β1/Smads signaling pathway in type 2 diabetic rats,so as to illustrate the effects of exogenous hydrogen sulfide on cardiac fibrosis of type 2 diabetic rats and the underlying mechanism.Methods:The rat model of type 2 diabetic mellitus was established by a single intraperitoneal injection of streptozotocin(STZ,40 mg/kg)in 40 healthy male Sprague-Dawley rats combined with high-glucose and high-fat diet for 4 weeks.Blood glucose levels were measured 3 and 5 days after streptozotocin injection using a hand-held glucometer,by tail vein puncture blood sampling.Only rats with blood glucose levels≥16.7 mmol/L on both days were defined as diabetic and used in the present study.After modeling was successful,all rats were randomly divided into the following 4 groups with 10 animals per group:Control group,NaHS group,DM group and DM+NaHS group.DM+NaHS group rats and NaHS group rats were intraperitoneally administered H2S donor sodium hydrosulfide(NaHS)at a dose of 100μmol/kg per day for 12 weeks,DM group rats and Control rats were intraperitoneally injected with an equivalent volume of physiological saline for 12 weeks with general condition and weight change of rats observed.After 12 weeks,fasting blood glucose(FBG)was measured in all groups,and left ventricular end diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular fractional shortening(LVFS),left ventricular ejection fraction(LVEF)and E/A ratio were measured by echocardiography.The degree of myocardial interstitial fibrosis was evaluated by Masson′s staining,the collagen volume fraction(CVF)of myocardial interstitium was measured by Image-Pro Plus 6.0 software.The protein expressions of TGF-β1,Smad7,p-Smad2/3 and CollagenⅠwere detected by Western blot.Results:Compared with Control group,the FBG of DM group was significantly increased,the systolic and diastolic function of the DM group was worsened,the myocardial interstitial collagen f

关 键 词：硫化氢 糖尿病心肌病 心肌间质纤维化 TGF-β1/Smads 

分 类 号：R587.2[医药卫生—内分泌]