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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