白藜芦醇对肾间质纤维化的干预研究

发布时间：2018-05-29 04:54

本文选题：慢性肾功能衰竭 + 肾间质纤维化　；参考：《南华大学》2014年硕士论文

【摘要】：目的观察白藜芦醇对单侧输尿管梗阻大鼠模型肾间质纤维化的干预研究。方法24只清洁级SD大鼠随机分为假手术组(A组)和手术组(B、C),每组各8只,手术组将大鼠进行单侧输尿管结扎的方法建立肾间质纤维化的动物模型,再分为模型对照组(B组)、白藜芦醇治疗组(C组)。均予以普通饲养,假手术组A和模型对照组B:以10ml/Kg等量生理盐水灌胃,白藜芦醇治疗组:给予25mg/kg.d白藜芦醇(溶解于生理盐水以10ml/Kg)灌胃,手术后第14天处死所有大鼠;检查各组术后第14天血清尿素氮(BUN)、肌酐(Cr),并观察各组大鼠UUO术后14天肾组织纤维化程度:1)用HE和Masson染色的方法观察肾组织纤维化程度及肾小管上皮细胞基底膜变化;2)用免疫组织化学的方法检测TGF-β1、Col I、Smad2/3、Smad7的蛋白表达水平。结果1)术后第14天血清尿素氮、肌酐:模型组较假手术组大鼠尿素氮、肌酐明显升高(P0.05),经白藜芦醇治疗后,大鼠尿素氮、肌酐明显下降(P0.05)。2)病理切片HE染色:模型组较假手术组大鼠肾间质损伤指数明显升高(P0.01);经白藜芦醇治疗后,较模型组其肾间质损伤指数明显降低(P0.05),较假手术组肾间质损伤指数增高(P0.01)。3)病理切片Masson染色:模型组胶原含量明显增高(P0.01),而白藜芦醇治疗后,胶原沉积明显减轻(P0.01)。4)免疫组化显示TGF-β1、Col I、Smad2/3、Smad7:假手术组肾间质内未见I型胶原表达,模型组可见大量I型胶原沉积,经白藜芦醇治疗后,较模型组其肾间质内I型胶原的表达明显减轻(P0.05);假手术组大鼠肾组织TGF-β1呈弱阳性表达,模型组TGF-β1表达较假手术组显著增高(P0.01),白藜芦醇治疗组TGF-β1表达较模型组显著下降(P0.05);假手术组大鼠肾组织Smad2/3呈弱阳性表达,模型组呈强阳性表达,而白藜芦醇治疗组则表达减弱(P0.01);假手术组肾组织Smad7表达较模型组明显增强,而白藜芦醇治疗组则Smad7表达较模型组增强(P0.01)。结论白藜芦醇可以通过影响肾组织Col I及TGF-β/Smads通路中Smad2/3、Smad7、TGF-β1表达,抑制肾间质纤维化,从而延缓肾功能衰竭。
[Abstract]:Objective to observe the effect of resveratrol on renal interstitial fibrosis in rats with unilateral ureteral obstruction. Methods Twenty-four clean SD rats were randomly divided into sham operation group (n = 8) and operation group (n = 8). Rats in operation group were treated with unilateral ureteral ligation to establish an animal model of renal interstitial fibrosis. They were divided into two groups: model control group B group and resveratrol treatment group C group. All rats were fed with normal feeding, sham operation group (A) and model control group (B) were treated with 10ml/Kg, resveratrol group was given 25mg/kg.d resveratrol (10 ml / kg) dissolved in normal saline. All rats were killed on the 14th day after operation. The serum urea nitrogen bun (bun) and creatinine (Cr) were examined on the 14th day after operation in each group, and the degree of renal fibrosis in each group was observed 14 days after UUO. The degree of renal fibrosis and the basement membrane degeneration of renal tubular epithelial cells were observed by HE and Masson staining. The protein expression of TGF- 尾 1 Col / Smad2 / 3 Smad7 was detected by immunohistochemical method. Results 1) on the 14th day after operation, serum urea nitrogen and creatinine: the urea nitrogen and creatinine in the model group were significantly higher than those in the sham operation group. After resveratrol treatment, the serum urea nitrogen in the model group was significantly higher than that in the sham operation group. He staining of pathological sections: the renal interstitial injury index in the model group was significantly higher than that in the sham operation group, and after resveratrol treatment, the renal interstitial injury index in the model group was significantly higher than that in the sham operation group. Compared with the model group, the renal interstitial injury index of the model group was significantly lower than that of the sham operation group, and the index of renal interstitial injury was higher than that of the sham-operated group. The Masson staining of pathological sections showed that the collagen content in the model group was significantly higher than that in the model group, but after resveratrol treatment, the collagen content in the model group was significantly higher than that in the control group. Collagen deposition significantly alleviated P0.01U. 4) Immunohistochemistry showed that TGF- 尾 _ 1Col / Smad2 / 3 / Smad7: no type I collagen was found in the renal interstitium of sham operation group, and a large number of type I collagen deposition was observed in model group after resveratrol treatment. Compared with the model group, the expression of type I collagen in the renal interstitium was significantly reduced in the model group, and the expression of TGF- 尾 1 was weakly positive in the renal tissue of the sham-operated group. The expression of TGF- 尾 1 in the model group was significantly higher than that in the sham operation group, and the expression of TGF- 尾 1 in the resveratrol treatment group was significantly lower than that in the model group, while the expression of Smad2/3 in the renal tissue of the sham-operated group was weakly positive, and the expression of TGF- 尾 1 in the model group was strongly positive. The expression of Smad7 in renal tissue of sham operation group was significantly higher than that of model group, while the expression of Smad7 in resveratrol treatment group was higher than that in model group. Conclusion resveratrol can inhibit renal interstitial fibrosis and delay renal failure by affecting the expression of Smad2 / 3 Smad7TGF- 尾 1 in Col I and TGF- 尾 / Smads pathway.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

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