Protective effect and mechanism of quercetin on cardiac and renal functions in rats with cardiorenal syndrome
OBJECTIVE To investigate the protective effect and mechanism of quercetin on the cardiac and renal functions of rats with cardiorenal syndrome(CRS)based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor kappa-B(NF-κB)signaling pathway.METHODS CRS model of SD rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion.Model rats were randomly separated into model group,quercetin low-dose group(35 mg/kg),quercetin high-dose group(70 mg/kg),high-dose of quercetin+740Y-P group(70 mg/kg quercetin+3.5 mg/kg PI3K/Akt/NF-κB signaling pathway activator 740Y-P),with 12 rats in each group.Another 12 normal rats were selected as sham operation group.They were given relevant drugs,once a day,for 14 consecutive days.After administration,the cardiac function indexes[left ventricular ejection fraction(LVEF),end-diastolic volume(EDV),isovolumic relaxation time(IVRT)]and renal function indicators[blood urea nitrogen(BUN),24-hour urine protein,and serum creatinine(Scr)]were detected,and fibrosis in the cardiac and renal tissues was observed;the levels of inflammatory indexes[interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)]in the serum and cardiac and renal tissues as well as the expression of PI3K/Akt/NF-κB pathway-related proteins in the cardiac and renal tissues were detected.RESULTS Compared with sham operation group,the levels of BUN,24-hour urine protein and Scr,collagen volume fraction of cardiac and renal tissues,the levels of IL-1β and TNF-α in serum and cardiac and renal tissues,and the phosphorylation of PI3K,Akt and NF-κB p65 protein in cardiac and renal tissues were increased significantly in model group(P＜0.05);the levels of LVEF,IVRT and EDV were reduced significantly(P＜0.05).Compared with the model group,the above indexes were reversed significantly in quercetin low-dose and high-dose groups(P＜0.05),and the reversal effect was better in the high-dose group(P＜0.05).740Y-P restored the reverse effect of high-dose quercetin on the indexes(P＜0.05).CONCLUSIONS Quercetin can alleviate cardiac and renal fibrosis and function injury,the mechanism of which may be associated with inhibiting the activation of the PI3K/Akt/NF-κB signaling pathway.
quercetinPI3K/Akt/NF-κB signaling pathwaycardiorenal syndromecardiac and renal functionfibrosis
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