Abstract: Objective To investigate the effects of resveratrol (RSV) on chronic kidney injury in high-fat mice by inhibiting endoplasmic reticulum (ER) stress response and its molecular mechanism. Methods Eighteen C57BL/6J mice were selected and randomly divided into three groups: the control group (CTRL group), high-fat group (HL group), and resveratrol group (RSV group), and a high-fat mouse model was established in HL and RSV group mice. RSV group was given a high-fat diet along with RSV 5 mg/(kg·d) lavage intervention. After 18 weeks, body weight, fasting blood glucose (FBG), low density lipoprotein cholesterol (LDL-C), low density lipoprotein cholesterol (HDL-C), uric acid (UA) and blood urea nitrogen (BUN) levels of mice in three groups were determined; the morphological changes of renal tissue in mice were observed with HE and PAS methods; the endoplasmic reticulum stress markers expression of CHOP, GRP78 protein and mRNA in kidney tissues were detected with western blot and RT-PCR methods. Results In RSV group, the body weight, FBG and LDL-C levels, serum UA and BUN levels were lower than those of HL group, while HDL-C level was higher than HL group, renal histopathological changes were improved, and the protein and mRNA expressions of ER stress markers CHOP and GRP78 were decreased. Conclusion RSV may improve chronic kidney injury in high fat diet mice by inhibiting the expression of endoplasmic reticulum markers CHOP and GRP78.

Key words: high-fat, chronic kidney injury, resveratrol, endoplasmic reticulum stress

摘要： 目的 探究白藜芦醇(RSV)通过抑制内质网应激反应改善高脂小鼠慢性肾损伤的作用及其分子机制。方法 选取18只C57BL/6J小鼠将其均分为3组,分别为对照组(CTRL组)、高脂组(HL组)、白藜芦醇组(RSV组),构建高脂模型。RSV组给予高脂饮食的同时进行RSV 5 mg/(kg·d)灌胃干预,18周后检测3组小鼠的体质量、空腹血糖(FBG)、低密度脂蛋白胆固醇(LDL-C)、低密度脂蛋白胆固醇(HDL-C)、尿酸(UA)和血尿素氮(BUN)的水平,采用HE、PAS染色观察小鼠肾组织的形态学变化,采用Western blot和RT-PCR法观察小鼠肾组织中内质网应激标志物CHOP、GRP78蛋白及mRNA的表达。结果 在给予RSV干预后,RSV组小鼠体重、FBG、LDL-C水平均低于HL组,HDL-C水平高于HL组,血清中UA和BUN均降低,肾组织形态学变化有所改善,内质网应激标志物CHOP、GRP78蛋白及mRNA的表达降低。结论 RSV主要通过抑制内质网标志物CHOP、GRP78的表达,改善高脂饮食诱导的慢性肾损伤。

关键词: 高脂, 慢性肾损伤, 白藜芦醇, 内质网应激