内源性H_2S对糖尿病肾病细胞外基质积聚的作用

目的观察糖尿病肾病(diabetic nephropathy,DN)大鼠肾组织中纤维黏连蛋白(fibronectin,FN)分布及含量变化,探讨内源性硫化氢(H2S)对糖尿病肾病细胞外基质积聚的作用。方法雄性SD大鼠28只用数字表法随机分为对照组、DN组、H2S干预组和胱硫醚-γ裂解酶(cystathionine-γ-lyase,CSE)阻断剂组,每组7只。用免疫组织化学法及Western blotting免疫印迹法检测各组大鼠肾组织中FN分布及含量。结果1)对照组大鼠FN主要分布于系膜基质和肾小囊壁;DN组和CSE阻断剂组大鼠肾小球基质中FN的分布增加;与DN组及CSE阻断剂组比较,H2S组大鼠FN的分布明显减少。2)与对照组比较,DN组大鼠FN的含量增加,Western blotting检测结果显示,DN组(48896±779)与对照组(38531±902)比较差异有统计学意义(P<0.01);与DN组、CSE阻断剂组比较,H2S组中FN的含量下降,Western blotting结果显示,H2S干预组(42737±1196)与DN组(48896±779)、CSE阻断剂组(48252±1068)比较,差异有统计学意义(P<0.01)。结论内源性H2S可抑制DN大鼠肾脏中细胞外基质的过度积聚,延缓糖尿病肾病的病理改变。

Role of Endogenous H2S in the Accumulation of Extracellular Matrix of the Diabetic Nephropathy

Objective To explore changes of fibronectin(FN) in the kidney tissues of diabetic nephropathy)(DN) rats, and to study the role of endogenous H₂S in the pathological development of diabetic nephropathy. Methods Twenty-eight rats(male, Sprague-Dawley) were randomly divided into four groups: control group, diabetic nephropathy group, DN+NaHS(H₂S donor) group and DN+DL-propargylglycine(PAG, H₂S synthetase inhibitor) group. Relative location and expression of FN in kidney tissues were measured respectively by Western blotting and immunohistochemistry. Results FN was positive in both the intraglomerular mesangial region and the extracellular matrix(EMC) in kidney tissues of DN group, and its expression level increased significantly. Western blotting: DN group (48 896±779) vs control group(38 531±902), P<0.01. Compared with that of DN group and DN+PAG group, NaHS significantly inhibited the over-expression of FN, Western blotting: DN+NaHS group(42 737±1 196) vs DN group(48 896±779) and DN+PAG group(48 252±1 068), P<0.01. Conclusion Endogenous H₂S can alleviate the pathological progression of DN by inhibiting the accumulation of ECM.