EGCG通过HIF-1α信号通路对顺铂诱导大鼠肾损伤的保护作用

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目的:研究EGCG(表没食子儿茶素没食子酸酯,Epigallocatechin-3-gallate)对顺铂(Cisplatin)诱导的大鼠肾损伤保护作用,并通过检测大鼠肾组织HIF-1α蛋白、mRNA的表达水平探讨其相关机制。方法:50只SD雄性大鼠(10只/组)按体重随机分为对照组、肾损伤组、EGCG 25 mg/kg、50 mg/kg、100 mg/kg不同剂量干预组。统计大鼠肾重量指数(KMI),分光光度计检测大鼠血清BUN、Cr的含量,HE染色观察大鼠肾组织病理损伤。RT-PCR法检测大鼠肾组织HIF-1α(hypoxia inducible factor-1,HIF-1)mRNA的表达水平;Western blot法检测大鼠肾组织HIF-1α蛋白表达水平。结果:肾损伤组中大鼠的肾重量指数明显升高,血清中BUN、Cr的含量明显升高,肾皮质HIF-1α蛋白含量升高,肾组织mRNA表达水平增加。肾损伤组中的大鼠肾组织HE染色结果中出现程度不等的部分肾小管扩张,较多肾小管上皮细胞变性、坏死脱落,基底膜裸露,腔内有大量红染无结构的颗粒状物质,较多肾小管腔内有蛋白管型。与肾损伤组相比,EGCG 50 mg/kg、100 mg/kg剂量组的大鼠肾重量指数明显降低,血清Cr含量降低,肾皮质HIF-1αmRNA、HIF-1α蛋白的含量有所升高,肾组织HE染色结果有所改善,肾小管上皮细胞变性、坏死脱落减轻,基底膜裸露情况减轻,腔内红染无结构的颗粒状物质减少,肾小管腔内蛋白管型减少。EGCG 25 mg/kg组中的大鼠肾组织上诉指标未见显著改善。结论:EGCG可能通过影响HIF-1α的表达,发挥其对缺血缺氧造成的肾损伤大鼠的保护作用。 OBJECTIVE: To study the protective effect of EGCG (Epigallocatechin-3-gallate) on Cisplatin-induced renal injury in rats and to detect the expression of HIF-1α protein and mRNA in rat kidney Level to explore its related mechanisms. Methods: Fifty SD male rats (10 rats / group) were randomly divided into control group, kidney injury group, EGCG 25 mg / kg, 50 mg / kg and 100 mg / kg intervention groups. Kidney weight index (KMI), the content of BUN and Cr in serum were detected by spectrophotometer. The pathological changes of rat kidney were observed by HE staining. The expression of HIF-1α mRNA in rat renal tissue was detected by RT-PCR. The protein expression of HIF-1α in renal tissue was detected by Western blot. Results: The renal weight index of rats in renal injury group was significantly increased, the levels of BUN and Cr in serum were significantly increased, the protein content of HIF-1α in renal cortex was increased, and the mRNA expression of renal tissue was increased. Renal injury in the rat kidney tissue HE staining results in varying degrees of tubular dilatation, more renal tubular epithelial cells degeneration, necrosis, basement membrane bare, the cavity has a large number of red dye unstructured particulate matter , More renal tubular cavity protein tube. Compared with the renal injury group, the renal weight index of rats in EGCG 50 mg / kg and 100 mg / kg groups were significantly decreased, while the content of serum Cr was decreased. The contents of HIF-1αmRNA and HIF-1α protein in renal cortex were increased, Renal tissue HE staining improved, renal tubular epithelial cells degeneration, necrosis shedding, basement membrane mitigation, intraluminal red staining of the structure of the particulate matter is reduced, tubular tubular protein decreased. There was no significant improvement in rat kidney tissue appetite in the EGCG 25 mg / kg group. Conclusion: EGCG may exert its protective effects on renal injury induced by hypoxia and hypoxia through affecting the expression of HIF-1α.
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