辛伐他汀通过增加脂联素及其受体的表达改善高脂饮食引起的肾脏损伤

摘要

目的:探讨辛伐他汀保护高脂饮食致肾脏损伤的新机制.方法:雌性SD大鼠随机分为标准饮食组、高脂饮食组及辛伐他汀治疗组,高脂饮食组和辛伐他汀治疗组先予高脂饮食20周,后者在高脂饮食的同时予辛伐他汀[10 mg/(kg·d)]灌胃治疗8周.分析大鼠血脂和肾脏的病理学变化、肾脏中脂联素、脂联素受体R1,R2,AMP依赖的蛋白激酶(AMPK),过氧化物酶体增殖物激活受体α(PPARα)、葡萄糖调节蛋白78(GRP78)和转录因子GADD153(CHOP)的表达.结果:高脂饮食组大鼠体质和血脂水平明显增高,脂联素及其受体表达明显下调,AMPKα磷酸化降低,PPARα表达降低,GRP78和CHOP基因表达水平均明显上调.辛伐他汀治疗组上述指标均出现明显改善.结论:辛伐他汀可能通过升高肾脏脂联素及其受体的表达,减少内质网应激来改善高脂诱导的大鼠肾脏损伤.%Objective To probe the new mechanism of simvastatin on high-fat diet-induced kidney dam-age. Methods Female SD rats were subjected to a standard control diet(SCD)or high-fat diet(HFD)for 20 weeks,then the HFD group was randomly divided into HFD group and HFD group with simvastatin treatment (HFD+ST,10mg·kg-1·d-1 )for another 8 weeks. The expression of adiponectin,adiponectin receptors R1 and R2, Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK),peroxisome proliferator-activated receptorα(PPARα),glucose regulated protein 78(GRP78)and GADD153(CHOP)in kidney were assessed respective-ly. Results Body weight and serum lipid levels in HFD group significantly increased ,expression of adiponectin and its receptors significantly down-regulated. Phosphorylation of AMPKα and PPARα expression decreased,and expression of GRP78 and CHOP up-regulated significantly. Above indexes in simvastatin treatment groups improved significantly. Conclusion Simvastatin can improve high-fat induced kidney damages ,probably by increasing expression of adiponectin and its receptors ,decreasing endoplasmic reticulum stress.