| Objective:To explore the Protective mechanism of Yiqi Xiefei Decoction(YXD)on myocardial tissue in chronic heart failure(CHF)by using Adriamycin-induced heart failure model.The diuretic test was used to verify the clinical efficacy of Yiqi Xiefei Decoction.Methods:1.Adriamycin(ADR)was used to induce chronic heart failure in Wistar rats.The rats were randomly divided into blank group,heart failure model group,Positive drug Qiliqiangxin capsule 0.33g/kg group,Yiqi Xiefei Decoction 17.5g raw drug/kg group,Yiqi Xiefei Decoction 8.75g raw drug/kg group,Yiqi Xiefei Decoction 4.38g raw drug/kg group.Yiqi Xiefei Decoction was administered continuously for 8 weeks.ThePhysiological indexes such as cardiac function and cardiac weight index were observed.The Physiological,biochemical and Pathological indexes such as cardiac function,myocardial cell injury,apoptosis,oxidative stress reaction,release of inflammatory factors and ultrastructural changes were observed by means of ELISA,HE,Masson,TUNEL,transmission electron microscopy and Western Blot to clarify the Preventive and therapeutic effect of Yiqi Xiefei Decoction on chronic heart failure and explore its mechanism.2.Male Wistar rats were randomly divided into blank group,Positive drug Qiliqiangxin Capsule 0.33g/kg group and Yiqi Xiefei Decoction 17.5g crude drug/kg group.The urine volume of animals was observed 0-2 hours and 2-4 hours after the last administration,and the total urine volume within 4 hours was calculated and compared between groups.Results:1.Effect of Adriamycin on Rat Model of Chronic Heart Failure1.1 Effect of Yiqi Xiefei Decoction on Cardiac Function in Adriamycin-induced Heart Failure RatsCompared with the blank group,the diastolic Pressure increased(p<0.01),the maximum left ventricular Pressure decreased(p<0.05),the maximum rate of increase(+dp/dt max)and the rate of decrease(-dp/dt max)of left ventricular Pressure decreased significantly in the model group(p<0.05,p<0.01).Compared with model group,the heart rate of Yiqi Xiefei Decoction 17.5g crude drug/kg group increased significantly(p<0.05);left ventricular systolic Pressure(LVSP),+dp/dt Max and-dp/dt Max increased significantly(p<0.01,p<0.05)in both Yiqi Xiefei Decoction 17.5g crude drug/kg group and 8.75g crude drug/kg group.1.2 Effect of Yiqi Xiefei Decoction on Heart Weight Index in Adriamycin-induced Heart Failure RatsCompared with the blank group,the weight of heart failure rats in the model group decreased significantly(p<0.001),and the weight of ascites increased significantly(p<0.001).Compared with model group,Yiqi Xiefei Decoction 17.5g crude drug/kg group could increase ascites weight and heart weight(p<0.01,p<0.05)and reduce ascites weight(p<0.05);Yiqi Xiefei Decoction 8.75g crude drug/kg group could increase heart weight(p<0.01),and increase heart weight index with ascites and heart weight index without ascites(p<0.05).Yiqi Xiefei Decoction 4.38g crude drug/kg group could increase heart weight(p<0.05).1.3 Effect of Yiqi Xiefei Decoction on Cell Morphology of Adriamycin-induced Heart Failure RatsHE staining showed that the left ventricular wall thickness of Yiqi Xiefei Decoction17.5g crude drug/kg group and 8.75g crude drug/kg group increased in varying degrees(p<0.05).Masson staining showed that the ratio of myocardial collagen distribution area in Yiqi Xiefei Decoction 17.5g crude drug/kg group and 8.75g crude drug/kg group decreased significantly compared with model group(p<0.05).TUNEL staining showed that the number of apoptotic Positive staining cells in Yiqi Xiefei Decoction 17.5g crude drug/kg group and 8.75g crude drug/kg group decreased significantly compared with model group(p<0.05).Ultrastructure was observed by transmission electron microscopy.The nucleus structure of Yiqi Xiefei Decoction 17.5g crude drug/kg group was normal;intercalated disc structure was close to normal;sarcomere structure on myofibrillar tract was clear and discernible,light and dark bands were clear;local mitochondria were increased and slightly dense,maintaining the complete structure of myocardial cells.1.4 Effect of Yiqi Xiefei Decoction on Serum Related Factor Levels in Adriamycin-induced Heart Failure RatsCompared with the blank group,the serum BNP content in the model group was significantly increased(p<0.001).Compared with model group,the content of BNP in serum was decreased in Yiqi Xiefei Decoction 17.5g crude drug/kg group and 8.75g crude drug/kg group(p<0.001,p<0.01).The results showed that compared with the blank group,the activity of SOD,MDA and GSH-PX in serum of the model group were significantly lower(p<0.001),higher(p<0.01)and lower(p<0.01).Compared with model group,Yiqi Xiefei Decoction 17.5g crude drug/kg group and 8.75g crude drug/kg group could increase SOD activity in serum(p<0.05),and Yiqi Xiefei Decoction 4.38g crude drug/kg group could significantly increase SOD activity in serum(p<0.001).1.5 Effect of Yiqi Xiefei Decoction on Related Factors in Myocardial Tissue of Adriamycin-induced Heart Failure RatsCompared with the blank group,the contents of RyR2 and ERCA in the myocardium of the model group decreased significantly(p<0.05),and the contents of Na+-K+-ATPase decreased.Compared with the model group,the Yiqi Xiefei Decoction 17.5g crude drug/kg group could increase the content of Na+-K+-ATPase(p<0.01),RyR2(p<0.01),Serca(p<0.05),and the Yiqi Xiefei Decoction 8.75g crude drug/kg group could increase the content of RyR2 in myocardial tissue(p<0.05).Compared with the blank group,the content of IL-6 and TNF-alpha in the myocardium of the model group increased significantly(p<0.05)and TNF-alpha increased significantly(p<0.01).Compared with model group,Yiqi Xiefei Decoction 17.5g crude drug/kg group could reduce the content of IL-6 in myocardial tissue(p<0.05).1.6 Effect of Yiqi Xiefei Decoction on Adriamycin-induced Heart Failure-related Proteins in RatsCompared with the blank group,the expression of CaM Protein increased in the model group,while the expression of CaMKII Protein increased significantly(p<0.05).Compared with model group,Yiqi Xiefei Decoction 17.5g crude drug/kg group,8.75g crude drug/kg group and 4.38g crude drug/kg group all reduced the expression of CaMKII Protein in myocardial tissue(p<0.05,p<0.01,p<0.01).Compared with the blank group,the expression of NF-kB Protein and TLR4 Protein increased significantly in the model group(p<0.05).Compared with the model group,Yiqi Xiefei Decoction 17.5g crude drug/kg group could reduce the expression of TLR4 Protein in myocardial tissue(p<0.05),and the expression of NF-kB Protein also decreased.Compared with the blank group,the expression of Bcl-2 Protein decreased(p<0.05),while the expression of Bax,caspase-3 and caspase-8protein increased(p<0.05),and the expression of caspase-9 also increased.Compared with model group,Yiqi Xiefei Decoction 17.5g crude drug/kg group increased the expression of Bcl-2 protein(p<0.05),and decreased the expression of Bax and caspase-3(p<0.05);in Yiqi Xiefei Decoction 8.75g crude drug/kg group,the expression of Bax protein decreased(p<0.05),and the expression of Bcl-2 protein increased(p<0.05);in the Yiqi Xiefei Decoction 4.38g crude drug/kg group,the expression of Bax in myocardium decreased(p<0.05).2.The effects on the Rats‘urine volumeThe results showed that compared with the blank group,the urine volume of Yiqi Xiefei Decoction 17.5g crude drug/kg group increased significantly during 2-4 hours and0-4 hours(p<0.05,p<0.01).Compared with the positive control group,the total urine volume of Yiqi Xiefei Decoction 17.5g crude drug/kg group increased significantly during0-2 hours,2-4 hours and 4 hours(p<0.05,p<0.01,p<0.001).Conclusion:1.From the histomorphological observation,Yiqi Xiefei Decoction can effectively protect myocardial tissue,reduce myocardial cell damage,myocardial fibrosis and ventricular wall muscle tension and prevent ventricular remodeling;Yiqi Xiefei Decoction can increase the content of Na~+-K~+-ATP,increase the content of RyR2 and Serca in myocardial tissue,reduce the expression of CaMk II protein in myocardial tissue,enhance positive myocardial strength and improve heart failure patients’heart rate.Muscle relaxation and contraction function;Yiqi Xiefei Decoction high dose group can reduce the content of IL6 in myocardial tissue,significantly inhibit the expression of TLR4 and NF-kappa B protein in myocardial tissue of rats with heart failure,thereby inhibiting inflammation;Yiqi Xiefei Decoction can significantly reduce the expression of caspase-8,caspase-3 and Bax protein,significantly increase the expression of anti-apoptotic Bcl-2protein,play an anti-apoptotic role,and consequently protect the myocardial tissue from APO Myocardial tissue,alleviating the development of heart failure.These may be the mechanism of Yiqi Xiefei Decoction in preventing and treating heart failure,which provides a new therapeutic target for clinical treatment of heart failure.2.The urine volume test showed that Yiqi Xiefei Decoction had the effect of purging lung and diuresis.The diuresis effect of Yiqi Xiefei Decoction on rats with 17.5g crude drug/kg was better than that of positive drug group. |
PDF Full Text Request