| Experimental goal:To study the therapeutic effect of Zhenwu Decoction on left coronary artery ligation induced heart failure in rats,and to explore the regulation effect and mechanism of Zhenwu Decoction on PINK1/Parkin pathway mediated mitochondrial autophagy in heart failure rats.Experimental Methods:Sixty SD male rats were randomly divided into 2 groups: sham operation group(ISS)(n = 10)and model group(n = 10)(model group MXZ,Losartan group LST,Zhenwu Decoction low-dose group ZWTD,Zhenwu Decoction medium-dose group ZWTZ and Zhenwu Decoction high-dose group ZWTG).The rat model of heart failure was established by left coronary artery ligation after thoracotomy with endotracheal intubation.Fourteen rats in the model group were randomly selected for preoperative and postoperative electrocardiogram examination;The sham operation group did not ligate coronary arteries after thoracotomy;Penicillin was injected for 3 consecutive days to prevent infection.M-type echocardiography was performed 8 weeks later.Rats in sham operation group and model group were given the same dose of normal saline intragastric administration,Losartan group was given losartan tablets 5mg/kg intragastric administration,Zhenwu Decoction low-dose,medium-dose and high-dose groups were given zhenwu Decoction granules 6g/kg,12g/kg and 18g/kg intragastric administration,respectively,Once a day for 28 days.The small animal ultrasound was performed again,Body weight,heart weight,left ventricular weight and serum BNP were measured,Changes of myocardial tissue were observed by HE staining,Ultrastructural changes of myocardium and mitochondria were observed by transmission electron microscopy,Protein contents of PINK1,Ρ-PINK1,Parkin,Ρ-parkin,LC3,P62 and Beclin1 related to the PINK1/ Parkin pathway were detected by Western blot.laboratory result:result1.Establishment of rat heart failure model: After ligation of the anterior descending branch of the left coronary artery,the myocardium surrounding the ligation turned white and an electrocardiogram was performed immediately: The ST segment presented a "giant R-type" elevation and fused with QRS wave,There was no such change in preoperative ecg;M-type echocardiography at 8 weeks postoperatively showed: Compared with the sham operation group,EF in the model group was significantly decreased(P<0.01),The average EF was less than 55%,Ventricular anterior wall contraction was not obvious in model group,The range of contraction was significantly lower than that of sham operation group;The rat model of heart failure was established successfully.Result2.Effect of Zhenwu Decoction on general state of heart failure rats:Compared with model group,the mental state of losartan group and Zhenwu decoction treatment group was improved,with shiny fur,increased activity and water intake,and black stool formation.Result3.Effects of Zhenwu Decoction on heart function in rats with chronic heart failure: compared with average EF before gavage,EF in model group was significantly decreased after gavage(P<0.01),losartan group significantly decreased after intragastric administration(P<0.05),there was no significant change after gavage in sham operation group and zhenwu Decoction low,medium and high treatment groups(P>0.05);Compared with sham operation group,BNP,LVIDs and LVIDd in model group were significantly increased(P<0.01),EF,FS,IVSs significantly decreased(P<0.01),IVSd decreased significantly(P<0.05);Compared with model group,BNP in losartan group was significantly decreased(P<0.01),LVIDs decreased significantly(P<0.05),no significant changes in EF,FS,IVSs,IVSd and LVIDd(P>0.05),BNP,LVIDs and LVIDd in zhenwu Decoction low-dose group were significantly decreased(P < 0.01),EF increased significantly(P<0.05),FS and IVSs were significantly increased(P<0.01),no significant improvement in IVSd(P>0.05),BNP and LVIDs in zhenwu Decoction medium-dose group were significantly decreased(P<0.01),EF,FS,IVSs increased significantly(P<0.01),no significant improvement in IVSd and LVIDd(P>0.05),BNP in zhenwu Decoction high-dose group was significantly decreased(P<0.01),LVIDs decreased significantly(P<0.05),EF increased significantly(P<0.01),FS and IVSs increased significantly(P<0.05),no significant improvement in IVSd and LVIDd(P>0.05).Result4.Effect of Zhenwu Decoction on heart function in rats with Heart failure: EF in model group was significantly lower than that before intragastric administration(P<0.01),EF in losartan group decreased significantly after gavage compared with before gavage(P < 0.05),There was no statistically significant difference in EF between sham operation group and zhenwu Decoction low-dose,medium-dose and high-dose groups after gavage(P<0.05);Compared with sham operation group,BNP,LVIDs and LVIDd in model group were significantly increased(P < 0.01),EF,IVSs and IVSd decreased significantly(P <0.05);Comparing the model group,BNP was significantly decreased in losartan group(P<0.01),LVIDs decreased significantly(P<0.05),EF,IVSs and IVSd did not increase significantly(P>0.05),LVIDd was not significantly decreased(P> 0.05),BNP,LVIDs and LVIDd in zhenwu Decoction low dose group were significantly decreased(P<0.01),EF increased significantly(P<0.05),IVSs significantly increased(P<0.01),no significant improvement on IVSd(P>0.05),BNP and LVIDs in zhenwu Decoction medium-dose group were significantly decreased(P < 0.01),EF and IVSs increased significantly(P < 0.01),no significant improvement on IVSd and LVIDd(P>0.05),BNP in zhenwu Decoction high-dose group was significantly decreased(P<0.01),LVIDs decreased significantly(P<0.05),EF increased significantly(P<0.01),IVSs significantly increased(P<0.05),no significant improvement in IVSd and LVIDd(P>0.05).Result5.Effect of Zhenwu Decoction on PINK1/ Parkin pathway related protein expression in chronic heart failure rats: Compared with sham operation group,P62 protein content in model group was significantly increased(P<0.01),LC3ⅱ,p-PINK1,p-parkin,Beclin1 protein content and LC3Ⅱ/ Ⅰ ratio were significantly decreased(P<0.01);Compared with model group,P62 in zhenwu Decoction low-dose,medium-dose and high-dose groups was significantly decreased(P<0.01),LC3Ⅱ,ρ-parkin,ρ-pin K1 protein content significantly increased(P < 0.01),LC3Ⅱ/Ⅰ and BECLIN1 in zhenwu Decoction group were significantly increased(P<0.05),LC3Ⅱ/Ⅰ and BECLIN1 in zhenwu Decoction medium-dose and high-dose groups were significantly increased(P<0.01).Conclusion:1.Zhenwu Decoction can improve the general condition of rats with heart failure,reduce serum BNP,inhibit the decrease of EF,reduce LVIDs,improve IVSs,improve cardiac function,inhibit myocardial fibrosis and myocardial cell swelling,and improve the ultrastructure of mitochondria in myocardial cells.2.Zhenwu Decoction may improve the utilization of damaged mitochondria,improve the energy supply of myocardium,inhibit ventricular hypertrophy and ventricular enlargement,improve the cardiac function of heart failure,and inhibit the progression of heart failure by enhancing the PINK1/Parkin signaling pathway mediated mitochondrial autophagy,so as to treat heart failure. |
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