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邢台市人民医院肾内科,河北 邢台 054000
Published:15 July 2024,
Received:17 January 2024,
Revised:19 May 2024,
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孔露娇,鲁华,王心等.槲皮素对心肾综合征大鼠心肾功能的保护作用及机制 Δ[J].中国药房,2024,35(13):1612-1617.
KONG Lujiao,LU Hua,WANG Xin,et al.Protective effect and mechanism of quercetin on cardiac and renal functions in rats with cardiorenal syndrome[J].ZHONGGUO YAOFANG,2024,35(13):1612-1617.
孔露娇,鲁华,王心等.槲皮素对心肾综合征大鼠心肾功能的保护作用及机制 Δ[J].中国药房,2024,35(13):1612-1617. DOI: 10.6039/j.issn.1001-0408.2024.13.12.
KONG Lujiao,LU Hua,WANG Xin,et al.Protective effect and mechanism of quercetin on cardiac and renal functions in rats with cardiorenal syndrome[J].ZHONGGUO YAOFANG,2024,35(13):1612-1617. DOI: 10.6039/j.issn.1001-0408.2024.13.12.
目的
2
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
2
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
2
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
2
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
2
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
2
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
2
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 grou
p (
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
2
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.
槲皮素PI3K/Akt/NF-κB信号通路心肾综合征心肾功能纤维化
PI3K/Akt/NF-κB signaling pathwaycardiorenal syndromecardiac and renal functionfibrosis
MCCALLUM W,SARNAK M J. Cardiorenal syndrome in the hospital[J]. Clin J Am Soc Nephrol,2023,18(7):933-945.
MCCALLUM W,TESTANI J M. Updates in cardiorenal syndrome[J]. Med Clin North Am,2023,107(4):763-780.
COSTANZO M R. The cardiorenal syndrome in heart failure[J]. Cardiol Clin,2022,40(2):219-235.
AMADOR-MARTÍNEZ I,APARICIO-TREJO O E,BERNABE-YEPES B,et al. Mitochondrial impairment:a link for inflammatory responses activation in the cardiorenal syndrome type 4[J]. Int J Mol Sci,2023,24(21):15875.
LIU J,ZONG C G,YU X,et al. Alanyl-glutamine (Ala-gln) ameliorates dextran sulfate sodium (DSS)-induced acute colitis by regulating the gut microbiota,PI3K-Akt/NF-κB/STAT3 signaling,and associated pulmonary injury[J]. ACS Infect Dis,2023,9(4):979-992.
CHEN K T,HUANG X X,XIE D X,et al. RNA interactions in right ventricular dysfunction induced type Ⅱ cardiorenal syndrome[J]. Aging,2021,13(3):4215-4241.
WANG Y Y,LIU Y Y,LI J,et al. Gualou xiebai decoction ameliorates cardiorenal syndrome type Ⅱ by regulation of PI3K/Akt/NF-κB signaling pathway[J]. Phytomedicine,2024,123:155172.
SITI H N,JALIL J,ASMADI A Y,et al. Effects of quercetin on cardiac function in pressure overload and postische-mic cardiac injury in rodents:a systematic review and meta-analysis[J]. Cardiovasc Drugs Ther,2022,36(1):15-29.
FENG Q,YANG Y,QIAO Y J,et al. Quercetin ameliorates diabetic kidney injury by inhibiting ferroptosis via activating Nrf2/HO-1 signaling pathway[J]. Am J Chin Med,2023,51(4):997-1018.
BAGHERI A,RADMAN G,ARIA N,et al. The effects of quercetin on apoptosis and antioxidant activity in a renal ischemia/reperfusion injury animal model[J]. Drug Res,2023,73(5):255-262.
王时光,刘攀,任超,等. 黄芪甲苷对心肾综合征大鼠的肾功能保护作用研究[J]. 中国临床药理学杂志,2023,39(3):363-367.
WANG S G,LIU P,REN C,et al. Protective effect of astragaloside Ⅳ on renal function in rats with cardiorenal syndrome[J]. Chin J Clin Pharmacol,2023,39(3):363-367.
JIANG C J,LI D,CHEN L,et al. Quercetin ameliorated cardiac injury via reducing inflammatory actions and the glycerophospholipid metabolism dysregulation in a diabetic cardiomyopathy mouse model[J]. Food Funct,2022,13(14):7847-7856.
王万民,田涛. 甲状腺功能亢进症模型大鼠心肌细胞PI3K/Akt通路与胰岛素抵抗的关系[J]. 广东医学,2020,41(24):2526-2530.
WANG W M,TIAN T. The correlation between PI3K/Akt pathway and insulin resistance in cardiomyocytes of rat models of hyperthyroidism[J]. Guangdong Med J,2020,41(24):2526-2530.
吴英智,李志梁,赖俊,等. 白术内酯Ⅰ对心肾综合征大鼠心肾功能的影响及机制[J]. 现代中西医结合杂志,2023,32(20):2788-2797.
WU Y Z,LI Z L,LAI J,et al. AtractylenolideⅠ protects cardiac and renal function of rats with cardiorenal syndrome via suppressing fibrosis synthesis[J]. Mod J Integr Tradit Chin West Med,2023,32(20):2788-2797.
GALLO G,LANZA O,SAVOIA C. New insight in cardiorenal syndrome:from biomarkers to therapy[J]. Int J Mol Sci,2023,24(6):5089.
GEORGOPOULOU T,PETRAKIS I,DERMITZAKI K,et al. Cardiorenal syndrome:challenges in everyday clinical practice and key points towards a better management[J]. J Clin Med,2023,12(12):4121.
LUO M,LIU Z Y,HU Z R,et al. Quercetin improves contrast-induced acute kidney injury through the HIF-1α/lncRNA NEAT1/HMGB1 pathway[J]. Pharm Biol,2022,60(1):889-898.
POVEDA J,VÁZQUEZ-SÁNCHEZ S,SANZ A B,et al. TWEAK-Fn14 as a common pathway in the heart and the kidneys in cardiorenal syndrome[J]. J Pathol,2021,254(1):5-19.
DU L,ZHANG J R,ZHANG X Y,et al. Oxypeucedanin relieves LPS-induced acute lung injury by inhibiting the inflammation and maintaining the integrity of the lung air-blood barrier[J]. Aging,2022,14(16):6626-6641.
TSUKAMOTO S,WAKUI H,UEHARA T,et al. Combination of sacubitril/valsartan and blockade of the PI3K pathway enhanced kidney protection in a mouse model of cardiorenal syndrome[J]. Eur Heart J Open,2023,3(6):oead098.
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