The Effect And Mechanism Of Resveratrol On Chronic Kidney Injury Induced By High-Lipid Diet In Mice

Background Due to the accelerated pace of life,the incidence of obesity-related diseases caused by unhealthy lifestyles such as high-fat diets and lack of exercise has increased year by year.Disorders of lipid metabolism,as an important component of metabolic syndrome(MS),are one of the common features of many primary and secondary kidney diseases.When the body has a disorder of lipid metabolism,it causes lipid deposition in the kidney and further progresses to kidney damage.Therefore,it is important to study the chronic kidney injury caused by lipid metabolism disorder and drug intervention.Resveratrol(RSV)is a polyphenolic compound found mainly in plants such as grapes and gourds.It has been confirmed that RSV has anti-inflammatory,anti-oxidation,anti-tumor,anti-platelet aggregation effects,and has the functions of protecting heart and cerebral ischemia.In recent years,it has been found to have renal protective effects and has been confirmed in animal models such as chronic renal failure,acute kidney injury,and diabetic nephropathy.The mechanism of resveratrol exerting renal protection is still unclear.It has been found that RSV can reduce renal inflammatory status by stimulating SIRT1 signaling pathway to protect kidney,inhibit inflammatory factor IL-6,TNF-α or reduce NO release.In this study,mice were fed a high-fat diet for a long time,and RSV intervention was added to study the pathological changes of renal tissue caused by high-fat diet,and to explore the protective mechanism of RSV on renal damage caused by high-fat diet.Objective To investigate the mechanism of long-term high-fat diet-induced renal injury in mice and the effect of RSV on renal tissue inflammatory response,oxidative stress and endoplasmic reticulum stress-related protein expression.Methods Eighteen 6-week-old C57BL/6J male mice were purchased from the Animal Center of Anhui Medical University and randomly divided into three groups: normal control group(CTRL)fed normal diet,high-lipid group(HL)fed high-fat diet,RSV intervention(RSV)group was intervention with resveratrol.After 18 weeks,blood was collected and sacrificed.The blood lipids(total cholesterol,triglyceride and high-density lipoprotein),body weight and renal function(creatinine,urea nitrogen)were measured in each group.One side of the kidney was selected to make paraffin.Sections,HE staining and PAS staining were used to study the morphological changes of renal tissues;immunohistochemistry was used to detect the expression of fibronectin(FN)in the kidney;Western blot and rt-pcr were used to detect the expression of antioxidant proteins SIRT1(sirtuin1),GPx4(glutathione peroxidase 4),SOD2(superoxide dismutase 2),stress marker GRP78(glucose-regulated protein 78)and CHOP(C/EBP homologous protein),and the expression of nuclear protein P65 of mice.SPSS19.0 was used for statistical analysis,(?)±s was used for all data and one-way anova was used.P<0.05 was considered statistically significant.Results(1)Blood biochemical indexes showed that serum levels of TC,TG,LDL and UA in the HL group were higher than those in the CTRL group,while HDL levels were lower(P < 0.05).Compared with HL group,serum TC,TG,LDL and UA levels in RSV group decreased,while HDL levels increased(P < 0.05).(2)Immunohistochemical staining of glomerular mesenchymal cells labeled with anti-FN monoclonal antibody showed that the positive expression of HL group was stronger than that of CTRL group,and the positive expression was weaker in RSV group than HL group;HE staining the results showed that RSV can improve the morphological changes of mouse kidney tissue induced by high-fat diet,improve mesangial proliferation and tubular fibrosis,and glycogen staining showed decreased glomerular glycogen deposition and decreased glomerular erythema.(3)The expression levels of antioxidant-related proteins SIRT1,SOD2 and GPx4 in HL group were significantly lower than those in CTRL group(P<0.05).Compared with HL group,RSV significantly up-regulated antioxidant-related proteins SIRT1,SOD2 and Expression of GPx4(P<0.05).(4)Compared with CTRL,the expression of GRP78,CHOP protein and m RNA in the HL group was up-regulated(P<0.05).GRP78 and CHOP m RNA expression levels in RSV group were significantly down-regulated compared with HL group(P<0.05).(5)The expression of p65 protein was up-regulated in HL group compared with CTRL group(P<0.05).RSV group could down-regulate p65 protein expression in RSV group compared with HL group(P<0.05).Conclusion The results of this study showed that the kidney tissue damage was obvious in the high-fat diet model group.RSV can inhibit the oxidative stress,endoplasmic reticulum stress and inflammatory reaction in the kidney tissue,and alleviate the chronic kidney injury caused by high-fat diet.