白藜芦醇减轻高脂饮食小鼠肾损伤的作用及机制

Effect and mechanism of resveratrol on chronic kidney injury induced by high-lipid diet in mice

目的研究高脂(HL)导致脂质代谢紊乱所引发慢性肾损伤的机制,并探讨白藜芦醇(RSV)在肾脏损伤中起保护作用的机制。方法选取6周龄雄性C57BL/6J小鼠造模,分设正常对照组(CTRL组)、高脂组(HL组)、白藜芦醇干预组(RSV组),18周后检测各组血脂、体质量和肾功能,采用HE染色、PAS染色和免疫组化法检测肾组织形态学变化;通过Western blot和RT-PCR方法检测小鼠肾组织氧化应激和内质网应激相关蛋白的表达。结果RSV明显降低高脂饮食小鼠的体质量、血脂和尿酸水平;改善肾小球系膜增生和肾小管纤维化,减少肾小球糖原沉积以及下调纤维黏连蛋白(FN)的表达;RSV明显上调抗氧化相关蛋白沉默信息调节因子2相关酶1(SIRT1)、超氧化物歧化酶2(SOD2)和谷胱甘肽过氧化物酶4(GPx4)的表达、下调内质网应激分子标志葡萄糖调节蛋白78(GRP78)和CCAAT增强子结合蛋白的同源蛋白(CHOP)的蛋白和mRNA表达。结论RSV通过抑制肾组织纤维化、氧化应激和内质网应激,减轻高脂饮食导致的慢性肾脏损伤。

Objective To investigate the protective effect of resveratrol(RSV)on kidney injury induced by high-lipid,and the mechanism unederlying.Methods Six-week-old male C57BL/6J mice were divided into following groups:normal diet(CTRL),high-lipid(HL)and RSV intervention(RSV)groups.After 18 weeks of high-fat diet,blood lipids,body weight and kidney function of mice were measured.Histomorphological changes in kidney were evaluated by HE staining and PAS staining.The expression of renal tissue oxidative stress and expression of endoplasmic reticulum stress-related proteins in mice was detected using immunohistochemistry,Western blot and RT-PCR.Results RSV significantly reduced the body weight,and blood lipid and uric acid of mice induced by high-fat diet.Furthermore,RSV improved mesangial proliferation and tubular fibrosis,and reduced glomerular glycogen deposition and down-regulated the expression of fibronectin.Most importantly,RSV significantly up-regulated the expression of antioxidant-related proteins silent information regulator factor 2 related enzyme 1,superoxide dismutase 2 and glutathione peroxidase 4,and down-regulated the endoplasmic reticulum stress molecular markers,glucose regulated protein 78 and CCAAT/enhancer binding protein-homologous protein at protein and gene levels.Conclusion These findings revealed that RSV has protective effect on high fat diet-induced chronic renal injury,the mechanism may relate to its inhibition of renal fibrosis,oxidative stress and endoplasmic reticulum stress.