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槲皮素对心肾综合征大鼠心肾功能的保护作用及机制
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| 篇名： | 槲皮素对心肾综合征大鼠心肾功能的保护作用及机制 |
| TITLE： | Protective effect and mechanism of quercetin on cardiac and renal functions in rats with cardiorenal syndrome |
| 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。 |
| ABSTRACT： | 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 |
| AUTHORS： | 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； |
| 阅读数： | 6 次 |
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