白芍总苷对心肌缺血再灌注大鼠心肌细胞焦亡及NLRP3炎症小体表达的影响  

Effects of Total Glucosides of Paeonia on NLRP3 Expression and Pyroptososis of Myocardial Cells of Myocardial Ischemia Reperfusion Rats

作　　者：郑亚萍[1] 刘春杰[1] ZHENG Yaping;LIU Chunjie(Luohe Medical College,Luohe 462002 Henan,China)

机构地区：[1]漯河医学高等专科学校,河南漯河462002

出　　处：《中药新药与临床药理》2019年第8期910-914,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：河南省科技攻关计划(社会发展领域)项目(182102310322);河南省科技厅基础与前沿研究重点研究项目(162300410268)

摘　　要：目的观察白芍总苷(TGP)对心肌缺血再灌注大鼠心肌细胞焦亡及NLRP3炎症小体表达的影响。方法将80只SD大鼠随机分为假手术组,模型组及TGP高、中、低剂量组(200、100、50 mg·kg-1),每天灌胃(20 mL·kg-1)给药1次,连续14 d。末次给药后制备大鼠心肌缺血再灌注模型。记录心电图T波变化,并通过BL-420F生物机能实验系统记录左心室收缩压(LVSP)、左心室舒张末期压力(LVEDP)、最大收缩期压力变化率(+dp/dtmax)及最大舒张期压力变化速率(-dp/dtmax);采用比色法测定肌酸激酶同功酶MB(CK-MB)、乳酸脱氢酶(LDH)活性;三苯基四氮唑(TTC)染色法测定心肌梗死面积;Western Blot法检测心肌组织核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、半胱氨酸天冬氨酸特异蛋白酶1(Caspase-1)、白细胞介素1β(IL-1β)、凋亡相关斑点样蛋白(ASC)表达;免疫组化法检测心肌组织巨噬细胞(ED1阳性细胞)的表达。结果与假手术组比较,模型组大鼠的T波、LVEDP,CK-MB、LDH活性,NLRP3、ASC、Caspase-1、IL-1β蛋白表达水平,心肌组织ED1阳性细胞表达率及心肌梗死面积百分率均显著升高(P <0.01);LVSP及±dp/dtmax显著降低(P <0.01)。与模型组比较,TGP高、中剂量组大鼠的T波、LVEDP,CK-MB、LDH活性,NLRP3、ASC、Caspase-1、IL-1β蛋白表达水平,心肌组织ED1阳性细胞表达率及心肌梗死面积百分率均显著降低(P <0.05,P <0.01);LVSP及±dp/dtmax显著升高(P <0.05,P <0.01)。结论 TGP能有效改善缺血再灌注的心脏功能,减少心肌梗死面积,其作用可能与抑制NLRP3介导的Caspase-1依赖的心肌细胞焦亡有关。Objective To investigate the effects of total glucosides of paeonia(TGP)on the expression of NLRP3 and on pyroptososis of myocardial cells of myocardial ischemia reperfusion rats.Methods Eighty Sprague-Dawley rats were randomly divided into Sham operation group,model group,high,middle and low dose groups of TGP(200,100,50 mg·kg-1).T wave changes of rats were measured with electrocardiogram.Left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),maximum systolic pressure change rate(+dp/dtmax)and the changing rate of maximum diastolic pressure(-dp/dtmax)were recorded using BL-420 F system.The activities of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)were detected by colorimetry.The myocardial infarction area was measured using TTC staining.The expression levels of myocardial nucleotide-binding oligomerization domain-like receptor protein3(NLRP3),Caspase-1,interleukin 1β(IL-1β)and apoptosis-associated speck-like protein containing a CARD(ASC)were measured by Western Blot.Immunohistochemical method was used to detect the expression of macrophages.Results Compared with Sham operation group,T wave,LVEDP,CK-MB,LDH activity,NLRP3,ASC,Caspase-1,IL-1βlevels,myocardial tissue macrophage expression and myocardial infarction area of model group rats were significantly increased(P<0.01),while LVSP,+dp/dtmaxand-dp/dtmaxwere significantly decreased(P<0.01).Compared with model group,T wave,LVEDP,CK-MB,LDH activity,NLRP3,ASC,Caspase-1,IL-1βlevels,myocardial tissue macrophage expression and myocardial infarction area were significantly decreased in high and middle low dose TGP group rats(P<0.05,P<0.01).LVSP,+dp/dtmaxand-dp/dtmaxwere significantly increased in high and middle dose TGP group rats(P<0.05,P<0.01).Conclusion TGP showed significant protective effect on myocardial ischemia reperfusion rats,which may be associated with NLRP3 induced Caspase-1-dependent myocardial pyroptososis.

关 键 词：心肌缺血再灌注 白芍总苷 细胞焦亡 核苷酸结合寡聚化结构域样受体蛋白3 半胱氨酸天冬氨酸特异蛋白酶1 

分 类 号：R285.5[医药卫生—中药学]