Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice  

作　　者：WEI Ya-ru HOU Yun-long YIN Yu-jie LI Zhen LIU Yi HAN Ning-xin WANG Zi-xuan LIU Lu WANG Xiao-qi HAO Yuan-jie MA Kun GU Jiao-jiao JIA Zhen-hua 

机构地区：[1]Graduate School,Hebei University of Chinese Medicine,Shijiazhuang,050090,China [2]Shijiazhuang Yiling Pharmaceutical New Drug Evaluation Center,Shijiazhuang,050035,China [3]Hebei Institute of Integrated Traditional and Western Medicine,Shijiazhuang,050035,China [4]National Key Laboratory for Innovation and Transformation of Luobing Theory,Shijiazhuang,050035,China [5]Department of Cardiology,Hebei Yiling Hospital,Shijiazhuang,050091,China [6]Graduate School,Hebei Medical University,Shijiazhuang,050017,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第7期608-615,共8页中国结合医学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No.81973692);Traditional Chinese Medicine Innovation Project of Hebei Province(No.223777120D);High-Level Talent Funding Program of Hebei(No.E2020100001)。

摘　　要：Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in mice.Methods A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min.According to a random number table,66 mice were randomly divided into 6 groups(n=11 per group):the sham group,the model group,the LY-294002 group,the TXL group,the TXL+LY-294002 group and the benazepril(BNPL)group.The day after modeling,TXL and BNPL were administered by gavage.Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks.Echocardiography was used to measure cardiac function in mice.Masson staining was used to evaluate the degree of myocardial fibrosis in mice.Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT)after MIRI was performed by immunohistochemistry,immunofluorescence staining and flow cytometry,respectively.The protein expressions of platelet endothelial cell adhesion molecule-1(CD31),α-smoth muscle actin(α-SMA),phosphatidylinositol-3-kinase(PI3K)and phospho protein kinase B(p-AKT)were assessed using Western blot.Results TXL improved cardiac function in MIRI mice,reduced the degree of myocardial fibrosis,increased the expression of CD31 and inhibited the expression ofα-SMA,thus inhibited the occurrence of EndMT(P<0.05 or P<0.01).TXL significantly increased the protein expressions of PI3K and p-AKT(P<0.05 or P<0.01).There was no significant difference between TXL and BNPL group(P>0.05).In addition,the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention,eliminated the protective effect of TXL,further supporting the protective effect of TXL.Conclusion TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关 键 词：myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway 

分 类 号：R285.5[医药卫生—中药学]