Adiponectin receptor mediated berberine to alleviate renal lipid toxicity in mice with diabetic kidney disease
Objective To explore whether adiponectin receptor 1/2(AdipoR1/R2)mediates berberine to alleviate renal lipid toxicity in mice with diabetic kidney disease.Methods C57BLKS/J db/db mice and db/m mice were selected and divided into 4 groups,with 8 in each group.db/db mice and db/m mice were given berberine(150 mg·kg-1·d-)or placebo by gavage for 12 weeks,respectively.After intervention,blood glucose,blood lipids,urinary microalbumin/creatinine ratio and urinary albumin excretion rate were determined.Kidney tissues were taken for pathological examination,and oil red O staining,immunohistochemistry,ELISA and Western blotting were used to examine lipid deposition,AdipoRl/R2 expression and fibrosis markers expressions,etc.,respectively.The human glomerular endothelial cell line(HGEC)was used to verify the role of AdipoR1/R2 in berberine alleviating renal lipid toxicity.Results After berberine intervention,the body weight,blood glucose,lipids,proteinuria,renal lipid deposition,and renal pathological changes decreased in db/db mice(P＜0.05);the expressions of AdipoR1 and AdipoR2 increased,expressions of TGF-β1 and Col-Ⅳ decreased,and the expressions of PPAR-α and p-AMPK increased in kidney tissue of db/db mice(P＜0.05).In high-fat cultured HGEC cells treated with berberine-treated db/db mouse serum,the expressions of TGF-β1 and Col-Ⅳ decreased,while the expressions of PPAR-α and p-AMPK increased(P＜0.05);after AdipoR1/R2 on HGEC cells were silenced,the expressions of TGF-β1 and Col-Ⅳ increased,while the expressions of PPAR-α and p-AMPK decreased(P＜0.05).Conclusions Berberine can reduce renal lipid toxicity in diabetic nephropathy mice,and adiponectin receptor may mediate this effect of berberine.
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