硫化氢对糖尿病大鼠心肌纤维化及PPARγ、NF-κB表达的影响

目的:初步探讨硫化氢(H2S)对糖尿病心肌纤维化的影响及其作用机制。方法:采用链脲佐菌素(STZ)单次腹腔注射的方法制作大鼠糖尿病模型,以硫氢化钠作为外源性H2S供体。将40只雄性SD大鼠随机分为对照组、STZ组、STZ+H2S组及H2S组,每组各10只。8周后处死大鼠,HE染色及VG染色观察心肌胶原分布情况,并用图像分析系统测量心肌间质胶原容积分数。Western blotting观察大鼠心肌组织中Ⅰ型胶原、PPARγ和NF-κB的表达水平。结果:与对照组相比,STZ组大鼠心肌组织胶原纤维明显增多,Ⅰ型胶原表达水平明显升高(P0.05),PPARγ表达明显减少(P0.05),NF-κB蛋白表达水平明显升高(P0.05)。与STZ组相比,STZ+H2S组心肌胶原纤维较少,Ⅰ型胶原表达明显降低(P0.05),PPARγ表达显著上调(P0.05),NF-κB蛋白表达显著降低(P0.05),而H2S组大鼠心肌组织Ⅰ型胶原、PPARγ以及和NF-κB蛋白表达水平较对照组均无显著差异。结论:硫化氢可改善糖尿病心肌纤维化,其内在机制可能与PPARγ-NF-κB途径有关。

Effect of hydrogen sulfide on myocardial fibrosis and PPARγ and NF-κB expression in rat model of diabetes

AIM: To explore the effects of hydrogen sulfide (H₂S) on the myocardial fibrosis in a rat model of diabetes and its mechanism.METHODS: Single intraperitoneal injection of streptozotocin (STZ) was utilized to establish a rat model of diabetes. Sodium hydrosulfide was used as an exogenous donor of hydrogen sulfide. Male SD rats were randomly divided into control group, STZ group, STZ+H₂S group and H₂S group. Eight weeks later, HE and VG staining methods were used to observe the collagen distribution and collagen volume fraction was measured by image analysis. The expression levels of type I collagen, PPARγ and NF-κB in the cardiac tissues were determined by Western blotting.RESULTS: Compared with control group, collagen distribution and the expression levels of type I collagen and NF-κB in the cardiac tissues were markedly increased (P<0.05), while PPARγ was significantly decreased in STZ group (P<0.05), but these indexes were reversed significantly in STZ+H₂S group (P<0.05). The expression levels of type I collagen, PPARγ and NF-κB had no significant difference between H₂S group and control group.CONCLUSION: Hydrogen sulfide attenuates cardiac fibrosis in diabetic rats, and its mechanism may be related to PPARγ-NF-κB signaling pathway.