摘要
目的:探讨丹参酮ⅡA(T-ⅡA)对于缓解大鼠心肌梗死(MI)后左心室重构(LVR)的作用及其机制。方法:选取SD雄性大鼠80只,通过结扎左前降支(LAD)建立MI大鼠模型。将大鼠随机分为8组,假手术组未结扎LAD,其余各组均结扎LAD;除假手术组和MI组腹腔注射生理盐水外,其余各组分别给予T-ⅡA、脂多糖(LPS)和TAK-242治疗。HE和马松(Masson)三色染色评估MI大小、组织病理改变和纤维化程度。末端dUTP镍末端标记(TUNEL)染色观察心肌细胞凋亡情况。采用反转录定量聚合酶链反应(RT-qPCR)和蛋白免疫印迹试验检测Toll样受体4(TLR4)、髓样分化蛋白88(My D88)和核因子κB(NF-κB)的表达水平。结果:T-ⅡA能改善MI大鼠心功能,可降低MI大鼠心脏体积,改善心脏形态,减轻MI大鼠的组织病理学改变,并有效减轻MI和心肌纤维化。T-ⅡA抑制MI大鼠的TLR4/MyD88/NF-κB信号通路,且能有效减少MI大鼠梗死边缘区心肌细胞凋亡。结论:T-ⅡA通过抑制TLR4/MyD88/NF-κB信号通路的激活,改善心脏形态、功能和病理组织学变化,有效减轻MI的严重程度,预防LVR。
Objective:To explore the effect of TanshinoneⅡA(T-ⅡA)on alleviating left ventricular remodeling(LVR)after myocardial infarction(MI)in rats and its Mechanism.Methods:80 male SD rats were selected to establish the MI rat model by ligation of the left anterior descending branch(LAD).The rats were randomly divided into 8 groups.Sham operation group was not ligated LAD,and the other groups were all ligated LAD.Except for the sham operation group and the MI group by intraperitoneal injection of normal saline,the other groups were treated with T-ⅡA,lipopolysaccharide(LPS)and TAK-242 respectively.MI size,histopathological changes,and fibrosis degree were assessed by HE and Masson trichromatic staining.The apoptosis of cardiomyocytes was observed by TdT-mediated d UTP nick end labeling(TUNEL).The expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor(My D88)and nuclear factor-κB(NF-κB)were detected by reverse transcriptional quantitative polymerase chain reaction(RT-qPCR)and Western blot.Results:T-ⅡA can improve the heart function of MI rats,reduce the volume of the heart of MI rats,improve the shape of the heart,reduce the histopathological changes in MI rats,and effectively reduce MI and myocardial fibrosis.T-ⅡA inhibits the TLR4/MyD88/NF-κB signaling pathway in MI rats,and can effectively reduce cardiomyocyte apoptosis in the marginal zone of infarction in MI rats.Conclusion:T-ⅡA inhibits the activation of the TLR4/MyD88/NF-κB signaling pathway,improves cardiac morphology,function and histopathological changes,effectively reduces the severity of MI,and prevents LVR.
作者
杨玉春
周晓欢
王姣
张雷
何鹏义
木胡牙提
YANG Yu-chun;ZHOU Xiao-huan;WANG Jiao;ZHANG Lei;HE Peng-yi;Muhuyati(Department of Comprehensive Cardiology,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang,830054,China)
出处
《现代生物医学进展》
CAS
2021年第22期4217-4222,4261,共7页
Progress in Modern Biomedicine
基金
国家自然科学基金项目(81860066)。
关键词
丹参酮ⅡA
心肌梗死
左心室重构
信号通路
Tanshinone IIA
Myocardial infarction
Left ventricular remodeling
Signaling pathway
