外源性硫化氢对糖尿病肾病大鼠肾纤维化的影响及机制

发布时间：2018-08-04 07:55

【摘要】：目的探讨外源性硫化氢(H2S)对糖尿病肾病大鼠肾纤维化的影响及其机制。方法将27只健康雄性SD大鼠腹腔注射链尿佐菌素(STZ)建立2型糖尿病模型,8周后建立糖尿病肾病模型。选取糖尿病肾病模型大鼠20只,另选取正常大鼠20只,分为正常对照组(Control+saline组)、H2S对照组(Control+Na HS组)、模型组(DN+saline组)、H2S治疗组(DN+Na HS组),每组10只。予以DN+saline组和Control+Na HS组大鼠腹腔注射Na HS溶液100μmol/(kg·d),予以Control+saline组和DN+saline组腹腔注射等量生理盐水。持续8周后,收集24 h尿液,采用考马斯亮蓝G-250法检测24 h尿蛋白定量(24 h Upro);心脏采血、留取血清,采用全自动生化分析仪检测血清尿素氮(BUN)、肌酐(Scr)水平;取肾脏组织,采用HE染色法观察肾脏组织病理学表现,Western blotting法检测肾脏组织转化生长因子β1(TGF-β1)、Smad7蛋白表达,免疫组化法检测肾脏纤维化相关蛋白纤维连接蛋白(FN)、层粘连蛋白(LN)、ɑ-平滑肌肌动蛋白(ɑ-SMA)表达。结果与Control+saline组相比,DN+saline组大鼠BUN、SCr和24 h Upro升高(P均0.05),肾脏病理损伤明显加重,肾脏组织FN、LN、ɑ-SMA、TGF-β1蛋白表达上调(P均0.05),Smad7蛋白表达下调(P0.05);与DN+saline组相比,DN+Na HS组大鼠BUN、SCr、24 h Upro降低(P均0.05),肾脏病理损伤明显减轻,肾脏组织FN、LN、ɑ-SMA、和TGF-β1蛋白表达下调(P均0.05),Smad7蛋白上调(P均0.05)。结论外源性H2S可明显改善糖尿病肾病大鼠的肾纤维化,其机制可能与调控TGF-β1/Smad7信号通路有关。
[Abstract]:Objective to investigate the effect and mechanism of exogenous hydrogen sulfide (H 2S) on renal fibrosis in diabetic nephropathy rats. Methods 27 healthy male SD rats were injected with streptozotocin (STZ) to establish diabetic nephropathy model after 8 weeks. Twenty diabetic nephropathy model rats and 20 normal rats were divided into normal control group (Control saline group), H2S control group (Control Na HS group), model group (DN saline group), H2S treatment group (DN Na HS group), 10 rats in each group. Rats in DN saline group and Control Na HS group were intraperitoneally injected with 100 渭 mol/ (kg d), NaHS solution. The Control saline group and DN saline group were given intraperitoneal injection of the same amount of normal saline. After 8 weeks, 24 h urine was collected, 24 h urine protein was measured by Coomassie brilliant blue G-250 method (24 h Upro); heart blood was collected, serum urea nitrogen (BUN), creatinine (Scr) was detected by automatic biochemical analyzer, renal tissue was taken. The expression of transforming growth factor 尾 1 (TGF- 尾 1) Smad7 protein in renal tissue was detected by HE staining and Western blotting. The expression of fibronectin (FN), laminin (LN),) and smooth muscle actin (SMA) was detected by immunohistochemistry. Results compared with Control saline group, the BUNS SCR and 24 h Upro in DN saline group were higher than those in Control saline group (P 0. 05). Compared with DN saline group, the expression of Smad7 protein decreased at 24 h (P 0.05), and the pathological damage of kidney was alleviated. The expression of FNLN, -SMA-TGF- 尾 1 and TGF- 尾 1 protein were down-regulated (P 0.05) and Smad7 protein was upregulated (all P 0.05). Conclusion exogenous H 2S can significantly improve renal fibrosis in diabetic nephropathy rats, and its mechanism may be related to the regulation of TGF- 尾 1/Smad7 signaling pathway.
【作者单位】：西南医科大学附属医院;
【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(0903-100020802)
【分类号】：R587.2;R692.9

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