槲皮素对心肾综合征大鼠心肾功能的保护作用及机制  

Protective effect and mechanism of quercetin on cardiac and renal functions in rats with cardiorenal syndrome

作　　者：孔露娇 鲁华[1] 王心 李帅 刘静[1] 郭晓阳 KONG Lujiao;LU Hua;WANG Xin;LI Shuai;LIU Jing;GUO Xiaoyang(Dept.of Nephrology,Xingtai People’s Hospital,Hebei Xingtai 054000,China)

机构地区：[1]邢台市人民医院肾内科,河北邢台054000

出　　处：《中国药房》2024年第13期1612-1617,共6页China Pharmacy

基　　金：河北省2023年度医学科学研究课题计划项目(No.20232016)。

摘　　要：目的 基于磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/核因子κB(NF-κB)信号通路探讨槲皮素对心肾综合征(CRS)大鼠心肾功能的保护作用及机制。方法 取SD大鼠,采用左冠状动脉前降支结扎结合肾急性缺血再灌注的方法构建CRS模型,将造模成功的大鼠随机分为模型组、槲皮素低剂量组(35 mg/kg)、槲皮素高剂量组(70 mg/kg)、槲皮素高剂量+740Y-P组(70 mg/kg槲皮素+3.5 mg/kg PI3K/Akt/NF-κB信号通路激活剂740Y-P),每组12只;另取12只正常大鼠设为假手术组。每天给药1次,连续14 d。给药结束后,检测大鼠心功能指标[左心室射血分数(LVEF)、舒张末期容积(EDV)、等容舒张时间(IVRT)]与肾功能指标[血尿素氮(BUN)、血肌酐(Scr)、24 h尿蛋白];观察大鼠心肾组织纤维化情况;检测大鼠血清与心肾组织中炎症指标[白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)]水平及心肾组织中PI3K/Akt/NF-κB信号通路相关蛋白表达。结果 与假手术组比较,模型组大鼠BUN、24 h尿蛋白、Scr水平,心肾组织的胶原容积分数,血清与心肾组织中IL-1β、TNF-α水平,心肾组织中PI3K、Akt、NF-κB p65蛋白磷酸化水平均显著升高(P<0.05),LVEF、IVRT、EDV均显著降低(P<0.05)。与模型组比较,槲皮素低、高剂量组大鼠上述指标均显著改善(P<0.05),且高剂量组的改善效果更好(P<0.05)。740Y-P逆转了高剂量槲皮素对各指标的改善作用(P<0.05)。结论 槲皮素可减轻CRS大鼠心肾纤维化和功能损伤,其作用机制可能与抑制PI3K/Akt/NF-κB信号通路激活有关。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-1βand TNF-αin 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 querceti

关 键 词：槲皮素 PI3K/Akt/NF-κB信号通路 心肾综合征 心肾功能 纤维化 

分 类 号：R965[医药卫生—药理学]