达格列净调控JAK2/STAT3轴对大鼠缺血性室性心律失常的作用  

Effects of dapagliflozin on ischemic ventricular arrhythmia in rats by regulating JAK2/STAT3 axis

作　　者：凌静 吴瑶 田国平 LING Jing;WU Yao;TIAN Guo-ping(Department of Functional Examination,the Second Hospital,University of South China,Hengyang 421001,Hunan Province,China;Department of Cardiovascular Medicine,the Second Hospital,University of South China,Hengyang 421001,Hunan Province,China)

机构地区：[1]南华大学附属第二医院功能检查科,湖南衡阳421001 [2]南华大学附属第二医院心血管内科,湖南衡阳421001

出　　处：《中国临床药理学杂志》2024年第3期388-392,共5页The Chinese Journal of Clinical Pharmacology

基　　金：湖南省自然科学基金资助项目(2021JJ30608)。

摘　　要：目的 探讨达格列净(DAPA)调控蛋白酪氨酸激酶2(JAK2)/信号转导子与激活子3(STAT3)轴对大鼠缺血性室性心律失常(VA)的作用及机制研究。方法 将大鼠随机分为假手术组、模型组和低、中、高剂量实验组及AG490组,每组10只。除假手术组外各组用结扎冠状动脉左前降支(LAD)构建大鼠缺血性VA模型。造模后48 h,低、中、高剂量实验组分别给予大鼠1、3、5 mg·kg^(-1) DAPA灌胃,AG490组灌胃5 mg·kg^(-1) DAPA+5 mg·kg^(-1) AG490,每日1次,持续30 d。用心电图检查大鼠心律失常评分,用蛋白质印迹法检测心肌组织中磷酸化JAK2(p-JAK2)/JAK2和磷酸化STAT3(p-STAT3)/STAT3蛋白的表达水平。结果 假手术组、模型组、低、中、高剂量实验组和AG490组的心律失常评分分别为(0.00±0.00)、(4.36±0.52)、(3.41±0.42)、(2.84±0.33)、(2.13±0.26)和(3.74±0.43)分,p-JAK2/JAK2相对表达水平比值分别为0.98±0.10、0.41±0.05、0.62±0.07、0.74±0.08、0.91±0.09和0.52±0.06,p-STAT3/STAT3相对表达水平比值分别为0.93±0.09、0.33±0.04、0.57±0.06、0.78±0.08、0.89±0.09和0.49±0.05。模型组的上述指标与假手术组、低、中、高剂量实验组比较,AG490组的上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论 DAPA可能通过激活JAK2/STAT3信号通路,抑制炎症反应和氧化应激,改善大鼠缺血性VA。Objective To investigate the effect and mechanism of dapagliflozin(DAPA) on ischemic ventricular arrhythmia(VA) in rats by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) axis.Methods The rats were randomly divided into sham operation group,model group,experimental-L,-M,-H groups and AG490 group.All groups except sham group were established model of ischemic VA by ligation of the left anterior descending coronary artery(LAD).After 48 h of modeling,the experimental-L,-M,-H groups were given 1,3,5 mg·kg^(-1) DAPA by gavage,respectively;the AG490 group were given 5 mg·kg^(-1) DAPA+5 mg·kg^(-1) AG490 by gavage,once a day for 30 days.The arrhythmia scores of rats were examined by electrocardiogram;the expression levels of phosphorylated JAK2(p-JAK2)/JAK2 and phosphorylated STAT3( p-STAT3)/STAT3 proteins in myocardial tissue were detected by Western blotting.Results The arrhythmia scores of the sham operation group,model group,experimental-L,-M,-H groups and AG490group were( 0.00 ± 0.00),( 4.36 ± 0.52),( 3.41 ± 0.42),( 2.84 ± 0.33),( 2.13 ± 0.26) and( 3.74 ± 0.43)points;the relative expression levels of p-JAK2/JAK2 were 0.98 ± 0.10,0.41 ± 0.05,0.62 ± 0.07,0.74 ± 0.08,0.91 ± 0.09 and 0.52 ± 0.06;the relative expression levels of p-STAT3/STAT3 were 0.93 ± 0.09,0.33 ± 0.04,0.57 ± 0.06,0.78 ± 0.08,0.89 ± 0.09 and 0.49 ± 0.05,respectively.There were significant differences in the above indexes between the model group and the sham operation group,experimental-L,-M,-H groups( all P < 0.05);compared with the experimental-H group,the difference of AG490 was statistically significant( all P < 0.05).Conclusion DAPA may improve ischemic VA in rats by activating the JAK2/STAT3 signaling pathway and inhibiting inflammatory response and oxidative stress.

关 键 词：缺血性室性心律失常 达格列净 蛋白酪氨酸激酶2/信号转导子与激活子3 

分 类 号：R972[医药卫生—药品]