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苦参素通过JAK2/STAT3通路抑制心肌缺血再灌注大鼠炎症反应

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目的:探讨苦参素对心肌缺血再灌注(MIR)大鼠炎症反应的影响,并以 Janus 激酶 2(JAK2)/信号转导与转录激活子 3(STAT3)通路为切入点探讨其可能的作用机制。方法:将144只大鼠按随机数字表法分为6组:假手术组、模型组、维拉帕米(6 mg/kg)组和苦参素低剂量(25 mg/kg)、中剂量(50 mg/kg)、高剂量(100 mg/kg)组,每组 24只。造模前 7d开始每日 1次腹腔注射给药。末次给药 30 min后,通过阻断左冠状动脉前降支 30 min构建MIR大鼠模型。再灌注 24h后,观察心电图ST段变化,通过生物机能系统测定左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左心室内压最大升高速率(+dp/dtmax)和最大下降速率(-dp/dtmax);分光光度法检测血浆心肌酶[肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)]活性;通过 2,3,5-氯化三苯基四氮唑(TTC)染色、苏木素-伊红(HE)染色观察心肌梗死率和心肌组织病变;酶联免疫吸附实验(ELISA)法检测心肌组织炎性因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)]含量;蛋白质印迹法(Western Blot)检测 JAK2/STAT3 通路蛋白和高迁移率族蛋白 B1(HMGB1)表达。结果:苦参素预处理可明显降低 MIR大鼠心电图 ST段高度、LVEDP、心肌梗死率、血浆 CK-MB、LDH活性、心肌组织 TNF-α、IL-1β、IL-6含量及磷酸化 JAK2(p-JAK2)/JAK2、磷酸化 STAT3(p-STAT3)/STAT3 表达比值和 HMGB1 相对表达量,可明显升高 LVSP、+dp/dtmax、-dp/dtmax,差异均有统计学意义(P<0。05)。苦参素上述作用具有一定的剂量依赖性,苦参素高剂量组作用最强。除+dp/dtmax、-dp/dtmax外,苦参素高剂量组对其他指标的作用均优于维拉帕米组(P<0。05)。结论:苦参素可能通过抑制JAK2/STAT3通路活化而减轻 MIR大鼠炎症反应,对 MIR大鼠心脏功能起保护作用。
Effect of Oxymatrine on Inflammatory Response in Rats with Myocardial Ischemia-reperfusion
Objective:To investigate the effect of Oxymatrine on the inflammatory response of myocardial ischemia-reperfusion(MIR)rats.Methods:According to the random number table method,144 rats were divided into 6 groups:sham operation group,model group,verapamil(6 mg/kg)group,and Oxymatrine low-dose(25 mg/kg),medium-dose(50 mg/kg),high-dose(100 mg/kg)groups,with 24 rats in each group.The rats were administered by intraperitoneal injection once a day for 7 days before modeling.Thirty minutes after the last administration,the rat left anterior descending coronary artery was blocked for 30 minutes.After reperfusion twenty-four hours,the ST segment changes of the electrocardiogram were observed,the left ventricular systolic pressure(LVSP)and end-diastolic pressure(LVEDP),the maximum rise rate of left ventricular pressure(+dp/dtmax)and the maximum drop rate of left ventricular pressure(-dp/dtmax)were detected by biological function system.The activity of myocardial enzymes[creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)]in plasma were detected by spectrophotometry.The myocardial infarction rate and myocardial tissue lesions were observed by 2,3,5-triphenyl tetrazolium chloride(TTC)staining and hematoxylin-eosin(HE)staining.The contents of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6]in myocardial tissue were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway proteins and high mobility group box 1(HMGB1)were detected by Western Blot.Results:Oxymatrine pretreatment could significantly reduce ST segment height,LVEDP,myocardial infarction rate,CK-MB,and LDH activities in plasma,TNF-α,IL-1β,IL-6 contents in myocardial tissue,the expression ratio of p-JAK2/JAK2,p-STAT3/STAT3 and the relative expression of HMGB1,and it could significantly increase LVSP,+ dp/dtmax,-dp/dtmax,all of the difference was significant(P<0.05).Oxymatrine pretreatment could significantly improve myocardial tissue lesions.The above effects of Oxymatrine showed certain dose dependence,and the high-dose Oxymatrine group showed the strongest effect.Except for +dp/dtmax and-dp/dtmax,the effects of Oxymatrine high-dose on other indexes were better than those of the verapamil group(P<0.05).Conclusion:Oxymatrine may reduce the inflammatory response in MIR rats by inhibiting the activation of JAK2/STAT3 pathway,and plays protective role on cardiac function in MIR rats.

myocardial ischemia-reperfusionOxymatrineJanus kinase 2/signal transducer and activator of transcription 3 pathwayinflammation responsecardiac functionexeperimental study

苗卫光、杨丽、孙志涛、李伟伟、仝飞

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邯郸市第二医院(河北邯郸 056001)

心肌缺血再灌注 苦参素 Janus激酶2/信号转导与转录激活子3通路 炎症反应 心脏功能 实验研究

河北省邯郸市科学技术研究与发展计划

1823208064ZC

2024

中西医结合心脑血管病杂志
中国中西医结合学会 山西医科大学第一医院

中西医结合心脑血管病杂志

CSTPCD
影响因子:1.463
ISSN:1672-1349
年,卷(期):2024.22(2)
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