槲皮素对心肾综合征大鼠心肾功能的保护作用及机制 点击下载
论文标题: 槲皮素对心肾综合征大鼠心肾功能的保护作用及机制
英文标题:
中文摘要: 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(35mg/kg)、槲皮素高剂量组(70mg/kg)、槲皮素高剂量+740Y-P组(70mg/kg槲皮素+3.5mg/kgPI3K/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14d。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)、24h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、24h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-κBp65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。
英文摘要: 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 20232016) associated with inhibiting the activation of the PI3K/Akt/NF-κB signaling pathway.
期刊: 2024年第35卷第13期
作者: 孔露娇;鲁华;王心;李帅;刘静;郭晓阳
英文作者: KONG Lujiao,LU Hua,WANG Xin,LI Shuai,LIU Jing,GUO Xiaoyang
关键字: 槲皮素;PI3K/Akt/NF-κB信号通路;心肾综合征;心肾功能;纤维化
KEYWORDS: quercetin; PI3K/Akt/NF-κB signaling pathway;
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