硫化氢对糖尿病大鼠心肌纤维化及基质金属蛋白酶7和缝隙连接蛋白43表达的影响

摘要

目的 探讨硫化氢(H2S)对糖尿病大鼠心肌纤维化及基质金属蛋白酶7(MMP-7)和缝隙连接蛋白43(Cx43)表达的影响.方法 将52只SD大鼠随机分为4组,每组13只:糖尿病模型组(STZ组),硫化氢干预模型组(STZ+H2S组),硫化氢干预正常组(H2S组),正常对照组(Control组).予以链脲佐菌素(STZ)(40 mg/kg)处理STZ组和STZ+H2S,复制糖尿病大鼠模型,复制成功后,每天予以硫氢化钠NaHS溶液(100μmol/kg)处理STZ+H2S组与H2S组,予以等量生理盐水对Control组行腹腔注射,8周后将大鼠处死.VG染色观察4组大鼠心肌组织病理学改变,Western blot检测IV型胶原蛋白、MMP-7、Cx43蛋白的表达.结果 STZ组与Control组相比,STZ大鼠心肌细胞排列紊乱明显,细胞间胶原沉积增加,心室肌组织中Ⅳ型胶原蛋白及MMP-7蛋白表达增加(P<0.05),而Cx43蛋白表达降低(P<0.05);STZ+H2S组与STZ组相比,STZ+H2S组心肌细胞排列紊乱有所改善,细胞间胶原沉积减少,心室肌组织中Ⅳ型胶原蛋白及MMP-7蛋白表达也减少(P<0.05),Cx43蛋白表达上调(P<0.05).结论 H2S可改善糖尿病大鼠心肌纤维化,其机制可能与通过调控MMP-7上调Cx43蛋白表达有关.%Objective To investigate the effect of hydrogen sulfide on myocardial fibrosis and the expressions of connexin 43 (Cx43) and MMP7 in diabetic rats. Methods Fifty-two rats were randomly divided into four groups (13 in each): diabetes mellitus group (STZ group), diabetes mellitus treated with H2S group (STZ+H2S group), normal rats treated with H2S group (H2S group) and control group. The STZ group and the STZ+H2S group were treated with Streptozotocin according to the standard of 40 mg/kg to make diabetes model. After the modeling, NaHS (the provider of H2S, 100 μmol/kg) was administered to the rats of the STZ+H2S group and the H2S group every day; the rats in the control group were injected with equal amount of saline into peritoneal cavity. After 8 weeks, the pathological changes of myocardium in the four groups were observed by VG staining. The expression levels of collagen IV, MMP7 and Cx43 were analyzed by Western blot. Results Compared with the control group, the expression levels of collagen IV and MMP7 in the myocardial tissue were significantly increased (P < 0.05), while the expression level of Cx43 protein was significantly decreased in the STZ group (P < 0.05), accompanied by disorder of myocardial cells. Compared with the STZ group, the expression levels of collagen IV and MMP7 protein in the myocardial tissue were significantly decreased in the STZ+H2S group (P < 0.05), while the expression level of Cx43 was significantly increased (P < 0.05) and the disorder of myocardial cells was improved. Conclusions Hydrogen sulfide could reduce myocardial fibrosis in diabetic rats, which may be related to the upregulation of connexin 43 expression by MMP7.