

浏览全部资源
扫码关注微信
邢台市人民医院肾内科,河北 邢台 054000
Received:17 January 2024,
Revised:2024-05-19,
Accepted:20 May 2024,
Published:15 July 2024
移动端阅览
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 [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 [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.
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 .
0
Views
312
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
公网安备50010302001817