Gegen Qinlian Decoction(葛根芩连汤)Regulates Expression of HIF-2α,EPO,and GILUT4 in Renal Tissue of Obese Rat Model of Insulin Resistance and Hypoxia Predisposing to Type 2 Diabetes Mellitus
Objective:To investigate the effects of Gegen Qinlian Decoction(葛根芩连汤,GQD)on the expression of hypoxia-inducing factor-2α(HIF-2α),erythropoietin(EPO),and glucose transporter 4(GLUT4)in the renal tissue of the rat model of insulin resistance and hypoxia.Methods:Seventy-two SD rats were randomized into a normal control group and a modeling group.The rat model of insulin resistance and hypoxia was established by a high-fat diet for 13 weeks.The successfully modeled rats were randomized into model control,rosiglitazone(5 mg/kg),and GQD(1.65 g/kg and 14.85 g/kg)groups.Rats were administrated with corresponding drugs once a day for 16 consecutive weeks.The body mass,body length,and Lee's index were recorded.The radioimmunoassay was employed to measure the level of fasting in-sulin(FINS),an automatic biochemical analyzer was used to measure the levels of fasting blood glucose(FBG),serum creatinine(Scr),ure-a nitrogen(BUN),and uric acid(UA).HIF-2α and EPO were detected by enzyme-linked immunosorbent assay(ELISA).The morphologi-cal changes of the renal tissue were observed by hematoxylin-eosin(HE)staining.The mRNA and protein levels of Hif-2α,Epo,and Glut4 were determined by real-time quantitative PCR and Western blotting,respectively.Results:Compared with the normal control group,the model control group showed increased body weight,Lee's index,and homeostasis model assessment-insulin resistance(HOMA-IR)and ele-vated levels of FBG and FINS(P＜0.01).In addition,the model group presented up-regulated mRNA and protein levels of Hif-2α and Epo and down-regulated mRNA and protein levels of Glut4 in the renal tissue(P＜0.05,P＜0.01).Compared with the model control group,1.65 g/kg and 14.85 g/kg GQD decreased the body weight,Lee's index,and HOMA-IR,lowered the levels of FBG and FINS,down-regula-ted the mRNA and protein levels of Hif-2α and Epo,and up-regulated the mRNA and protein levels of GLUT4 in the renal tissue(P＜0.05 or P＜0.01).Conclusion:GQD can down-regulate the expression of HIF-2α and EPO and up-regulated the expression of GLUT4 in the model rats to alleviate insulin resistance and renal hypoxia,thereby delaying the occurrence and development of diabetic nephropathy.
Gegen Qinlian Decoction(葛根芩连汤)Type 2 diabetes mellitusInsulin resistanceHypoxiaHypoxia-inducing factor-2αErythropoietinGlucose transporter 4
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