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Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at infarct border zone through SIRT1-Mediated FOXO1 and NF-κB Pathways in Rat Model of Acute Myocardial infarction

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Chinese Journal of Integrative Medicine 2022年第4期28卷 330-338页

作者： TAN Yu BIE Yu-long CHEN Li ZHAO Yi-han SONG Lei MIAO Li-na YU Yan-qiao CHAI Hua MA Xiao-juan SHI Da-zhuo National Clinical Research Center for Chinese Medicine Cardiology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing100091China Peking University Traditional Chinese Medicine Clinical Medical School(Xiyuan Hospital) Beijing100191China Department of Graduate School Beijing University of Chinese MedicineBeijing100029China

Objective To investigate whether Lingbao Huxin Pill(LBHX)protects against acute myocardial infarction(AMI)at the infarct border zone(IBZ)of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1(SIRT1)-mediated forkhead box protein O1(FOXO1)and nuclear factor-κB(NF-κB)signaling pathways.Methods Six-week-old Wistar rats with normal diet were randomized into the sham,the model,Betaloc(0.9 mg/kg daily),LBHX-L(0.45 mg/kg daily),LBHX-M(0.9 mg/kg daily),LBHX-H(1.8 mg/kg daily),and LBHX+EX527(0.9 mg/kg daily)groups according to the method of random number table,13 in each group.In this study,left anterior descending coronary artery(LADCA)ligation was performed to induce an AMI model in rats.The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay.A TdT-mediated dUTP nick-end labeling(TUNEL)assay was conducted to assess cardiomyocyte apoptosis in the IBZ.The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain,Masson and hematoxylineosin(HE)staining assays.The expression levels of tumor necrosis factorα(TNF-α),interleukin(IL)-6,IL-1β,and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays(ELISAs).The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR(RT-qPCR).The protein expressions of SIRT1,FOXO1,SOD2,BAX and NF-κB p65 were detected by Western blot analysis.Results The ligation of the LADCA successfully induced an AMI model.The LBHX pretreatment reduced the infarct size in the AMI rats(P<0.01).The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ.Further,the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue(P<0.05),myocardial interstitial collagen deposition(P<0.05)and inflammation at the IBZ.The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats(P<0.05 or P<0.01).Furthermore,Western blot analysis revealed that the LBHX pretreatmen

关键词： Lingbao Huxin Pill Chinese medicine infarct border zone acute myocardial infarction SIRT1

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