1.Therapeutic effect and mechanism of Tongsaimai tablet on rats with acute myocardial infarction
Huailei GUO ; Gang TAN ; Xiuyun YANG ; Renxin XING
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(7):817-823
Objective To determine the effects of Tongsaimai tablet on cardiac function,myocardial injury,inflammation and fibrosis in rats with acute myocardial infarction(AMI)and investigate possible mechanism.Methods A total of 73 rats were subjected to establish rat model of AMI by ligation of the left anterior descending coronary artery.The 60 successfully modeled AMI rats were randomly divided into model group,p38 mitogen-activated protein kinase(MAPK)inhibitor group(10 mg/kg),low-and high-dose Tongsaimai tablet groups(0.28 and 0.56 g/kg),and high-dose Tongsaimai tablet+p38 MAPK inhibitor group(as above doses),with 12 rats in each group.Another 12 normal rats served as the sham operation group.After corresponding intervention for 14 d,echocardiography was applied to evaluate the heart function,including left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular ejec-tion fraction(LVEF),and left ventricular short axis shortening rate(LVFS).The levels of myo-cardial injury indexes[cardiac troponin Ⅰ(cTnⅠ),lactate dehydrogenase(LDH)]and inflammatory factors(TNF-α,IL-6,IL-10)were detected by ELISA.HE and Masson staining were used to ob-serve pathological changes and fibrosis in myocardial tissues.The expression of Collagen Ⅰ and Collagen Ⅲ in myocardial tissue was detected by immunohistochemical staining.The protein expression of p38 MAPK/matrix metalloproteinase(MMP)-9 pathway related proteins in myo-cardial tissues was detected by Western blotting.Results Compared with model group,the condi-tions were alleviated in the p38 MAPK inhibitor group,and low-and high-dose Tongsaimai tablet groups,with milder pathological damage in myocardial tissue,obviously decreased LVEDV,LVESV,cTnⅠ,LDH,TNF-α and IL-6 levels,CVF,expression of Collagen Ⅰ,Collagen Ⅲ,p-p38 MAPK/p38 MAPK and MMP-9,and increased LVEF,LVFS and IL-10 level(P<0.05).Com-pared with p38 MAPK inhibitor group and high-dose Tongsaimai tablet group,high-dose Tong-saimai tablet+p38 MAPK inhibitor group had LVEDV,LVESV,cTnⅠ,LDH,TNF-α,IL-6,CVF and Collagen Ⅰ,Collagen Ⅲ,p-p38 MAPK/p38 MAPK and MMP-9 decreased significantly,and LVEF[(64.31±7.78)%vs(52.89±7.05)%,(57.40±7.42)%]and LVFS[(34.51±5.29)%vs(27.02±5.01)%,(25.04±4.13)%]increased obviously(P<0.05).Conclusion Tongsaimai tab-let can improve cardiac function,myocardial injury,inflammation and fibrosis in AMI rats,which may be due to its inhibition of p38 MAPK/MMP-9 signaling pathway.