Traditional Chinese Medication Qiliqiangxin Attenuates Cardiac Remodeling After Acute Myocardial Infarction In Mice

Purpose:To study the effects and mechanism of Qiliqiangxin(QLQX) on cardiac remodeling after acute myocardial infarction in mice.Methods:Establish the acute myocardial infarction(AMI) mouse model by ligating the left anterior descending coronary artery(LAD). To determine the effects of QLQX on cardiac remodeling after AMI, mice were randomly divided into eight groups and were treated by intragastric administration as follows for 21 days:(i) sham operation+vehicle;(ii) sham operation+QLQX(0.25 g/kg/d);(iii) AMI+QLQX(0.25 g/kg/d);(iv) AMI+vehicle;(v) sham operation+ QLQX(0.5g/kg/d);(vi) AMI+QLQX(0.5g/kg/d);(vii) sham operation+QLQX(0.75g/kg/d); and(viii) AMI+QLQX(0.75g/kg/d). To determine if QLQX provide beneficial effects through PPAR-γ, mice were randomly divided into eight groups and were treated as follows for 21 days:(i) sham operation+vehicle;(ii) sham operation+QLQX(0.5 g/kg/d);(iii) AMI+vehicle;(iv) AMI+QLQX(0.5 g/kg/d);(v) sham operation+Rosiglitazone(PPAR-γ activator 1mg/kg/d);(vi) AMI+Rosiglitazone(PPAR-γ activator 1mg/kg/d);(vii) sham operation+T0070907(PPAR-γ inhibitor 1mg/kg/d); and(viii) AMI+T0070907(PPAR-γ inhibitor 1mg/kg/d). PPAR-γ activator and inhibitor were by intraperitoneal injection just after AMI. To clarify whether QLQX affects the acute injury or post-MI remodeling, mice were either treated with QLQX or vehicle for the first 3 days after infarction or from day 3 to day 21 at a dose of 0.5 g/kg/d.We analyzed the cardiac function, myocardial infarction size, fibrosis, apoptosis, and survival rate; and we also detected the expression level of some classical signal pathway, such as Akt, SAPK/JNK, ERK and PPAR-s family.Results:(1) The echocardiography showed a higher cardiac function with the administration of QLQX;(2) H&E, masson’s, TUNEL staining and survival analysis showed better cardiomyocyte architecture, lower fibrosis, apoptosis and a higher survival rate in QLQX groups;(3) QLQX attenuated cardiac remodeling but not infarction size;(4) QLQX didn’t affect the Akt, SAPK/JNK, ERK signal pathway; but increased the expression of PPAR-γ, with a stronger evidence from reverse experiment.Conclusions: QLQX increased heart function and survival rate, and reduced fibrosis and apoptosis after AMI in mouse. QLQX attenuated cardiac remodeling by increasing the expression of PPAR-γ.