Linggui Zhugan Decoction（苓桂术甘汤）Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Mice by Suppressing TGF-β 1/Smad Signaling Pathway

• 来源期刊: 中国结合医学杂志（英文版）
• 年，卷（期）: 2020,（5）
• 页码范围: 345-352
• 页数: 8页
• 语种: 英文
• DOI: 10.1007/s11655-018-3024-0

摘要

Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction (LZD,苓桂术甘汤)on the ventricular remodeling (VR) after acute myocardial infarction (AMI) and related mRNA and proteins expression in transforming growth factor-beta 1 (TGF-β1)/Smad signaling pathway,and explain its putative mechanism.Methods:A VR model was generated by ligation of coronary artery in mice.Two weeks after surgery,60 mice were randomly divided into the model group,the sham-operation group (distilled water),the positive control group (2.4 mg/kg simvastatin),and the low-,medium-and high-dose LZD groups (2.1,4.2,8.4 g crude drug/kg,respectively) by a random number table,10 mice in each group.Mice in each group was treated for 4 weeks.Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument.Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining.The expressions of TGF-β 1,Smad2,Srnad3,p-Smad2 and p-Smad3 in myocardial tissue were detected by Westem blotting.The mRNA expressions of TGF-β1,Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).The expressions of matrix metalloprotein 2 (MMP2),MMP9,collagen Ⅰ and collagen Ⅲ were observed by immunohistochemical methods.Results:VR mice showed significant dysfunction in hemodynamic indices and cardiac structure and function.Compared with the sham-operation group,myocardial tissue damage,interstitial fibrosis occurred in the model mice,left ventricular systolic pressure (LVSP),left ventricular pressure maximum contraction rate (+dp/dtmax) and left ventricular pressure maximum relaxation rate (-dp/dtmax) decreased significantly (all P＜0.01),while left ventricular end-diastolic pressure (LVEDP),cardiac weight index and left ventricular weight index elevated significantly,meanwhile TGF-β1,p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagen Ⅰ,collagen Ⅲ protein expressions in myocardial tissue and TGF-β1,Smad2 and Smad3 mRNA expressions increased significantly (all P＜0.01).Compared with the model group,LZD could significantly improve the pathological changes of myocardial tissue,increase LVSP,+dp/dtmax and-dp/dtmax,lower LVEDP,reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β 1,p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagen Ⅰ and collagen Ⅲ proteins in myocardial tissue and mRNA expressions of TGF-β1,Smad2 and Smad3 (P＜0.05 or P＜0.01).Conclusion:LZD can significantly suppress VR induced by AMI,and its underlying mechanism may be associated with its inhibitory effect on the TGF-β 1/Smad signaling pathway.