硫化氢对糖尿病大鼠心肌纤维化及缝隙连接蛋白43的影响

Effects of hydrogen sulfide on myocardial fibrosis and connexin 43 in diabetic rats

目的:探讨气体信号分子硫化氢(H2S)对糖尿病大鼠心肌Ⅰ型胶原蛋白和缝隙连接蛋白CX43的影响。方法:将大鼠随机分为4组:对照组、糖尿病组(STZ组)、硫化氢干预糖尿病组(STZ+H2S组)及硫化氢干预正常组(H2S组)。用腹腔注射链脲佐菌素(STZ)(40mg/kg)建立糖尿病模型;对照组每天腹腔注射0.9%氯化钠;STZ组与H2S组每天腹腔注射硫氢化钠(H2S供体)溶液(100μmol/kg)。8周后处死大鼠,免疫组织化学检测Ⅰ型胶原蛋白的表达,Western Blot检测CX43蛋白的表达。结果:与对照组相比,STZ组的CX43蛋白表达明显下降(P<0.001),而Ⅰ型胶原蛋白的表达明显增加(P<0.01);与STZ组相比,STZ+H2S组CX43蛋白表达上调(P<0.01),而Ⅰ型胶原蛋白的表达则明显减少(P<0.05)。结论:H2S可改善糖尿病大鼠心肌纤维化,并上调CX43蛋白的表达,H2S可能参与糖尿病大鼠的心肌结构重构和电重构的调控。

Objective：To explore the effects of hydrogen sulfide （H2S） on cardiac type I collagen and CX43 in diabetic rats myocardium. Method：Rats were divided into four groups randomly： control group, diabetes mellitus group （STZ group）, diabetes mellitus treated with H2 S group （STZ＋ H2S group）, normal rats treated with H2 S group （H2 S group）. Diabetic model was induced by intraperitoneal injections of streptozotocin （STZ） with 40 mg/ kg body weight; Control group was treated with saline every day （ip） ; Naris （100 μmol/kg, ip） was administered to rats of STZ＋ H2 S group and H2 S group. After 8 weeks, the expression of CX43 was analyzed by Western blot- ting, type 1 collagen content was detected by Immunohistochemical method. Result：Compared with control group, the expression of CX43 was significantly decreased （P〈0. 001）, while type I collagen content was increased in STZ group mice （P〈0.01） ： The expression of CX43 was significantly increased （P〈0.01） and type I collagen content was obviously decreased （P〈0.05） in STZ＋ H2 S group compared to STZ group. Conclusion： H2 S can im- prove myocardial fibrosis, and increase the expression of CX43 protein in diabetic rats, which indicates that H2S may participate in cardiac remodeling in structure and electricity in diabetic rats.