| Objective: Compare the effects of moxibustion,RAPA and 3-MA on general behavioral signs,heart mass and index,cardiac function index,serum BNP and the expression of autophagy-related proteins LC3 and Beclin-1 in myocardium,and to explore the possible mechanism of moxibustion in the treatment of CHF,and to provide further experimental evidence for moxibustion treatment of CHF.Methods: Sixty SD male rats were randomly divided into 15 cages(4/cage),randomly selected 3 cages(12)as normal group and another 12 cages(48)for modeling.The modeling method was intraperitoneally injected with ADR at a dose of 2 mg/kg,once a week for 12 weeks.After successful modeling,the rats were randomly divided into4 groups: model group,moxibustion group,3-MA group and RAPA group.Normal and model groups were fed normally without any treatment.Moxibustion group were treated by moxibustion stimulation of "Fei Shu"(BL13)and "Xin Shu"(BL15)20 mins a day for 3 weeks.RAPA group was treated with gavage of RAPA at a dose of 2 mg/kg,once a day for 3 weeks.3-MA group was treated with intraperitoneal injection of3-MA at a dose of 15 mg/kg,once a day for 3 weeks.After the treatment,the changes of the general behavioral signs were recorded.The heart rate,cardiac output,left ventricular systolic pressure,left ventricular end diastolic pressure,left ventricular pressure and ascending rate were measured by cardiac function measuring instrument.Weigh the rat heart mass.BNP kit was used to detect and calculate the serum BNP levels in each group.The relative expression of LC3 and Beclin-1 in myocardium of rats were detected and compared by western blot.Results: 1.The general behavioral signs of the model rats were significantly changed,the body weight was decreased,the heart mass was increased,and the whole body mass index was increased(P<0.05).There were significant changes in cardiac function index(P<0.05).At the same time,HE staining showed that the model rat myocardial cells arranged disorder and cytoplasmic vacuolization formation,myocardial fiber localized rupture and dissolution were changed significantly.2.During the treatment period,the general behavioral signs of asthma,diarrhea,appetite and mental state of moxibustion group and 3-MA group were improved in different degrees.The state of rats in RAPA group continued to deteriorate.3.The mass of the moxibustion group and the 3-MA group increased in different degrees,the quality of the whole heart was reduced and the whole heart mass index was significantly decreased(P<0.05).While there had no significant improvement in RAPA group(P>0.05).4.The cardiac function indexes of moxibustion group and 3-MA group were significantly improved(P<0.05).While the RAPA group had no significant change(P>0.05).There also had no significant change in 3-MA group and moxibustion group(P>0.05).5.The serum BNP levels in the model group were significantly increased(P<0.01).Moxibustion group and 3-MA group were significantly decreased(P<0.05).While the RAPA group had no significant change(P>0.05).6.The expression of autophagy-related proteins LC3-II and Beclin-1in the model group was significantly increased(P<0.05).3-MA group and moxibustion group were significantly decreased(P<0.05).While the RAPA group was up-regulated(P<0.05).There was no significant between 3-MA and moxibustion group(P> 0.05).Conclusion: 1.The rat CHF model can be successfully constructed by intraperitoneal injection of ADR and can be used to simulate clinical CHF disease.2.ADR myocardial toxicity may be associated with overactivation of cardiomyocyte autophagy activity,thereby accelerating cardiomyocyte death.3.In the process of CHF,autophagic activator RAPA can over-activate cardiomyocyte autophagy and accelerate myocardial injury,adversely affect myocardial improvement in CHF.4.In the process of CHF,autophagy inhibitor 3-MA can inhibit myocardial autophagy and reduce myocardial injury and produce a positive therapeutic effect.5.Moxibustion stimulation of "Fei Shu"(BL13)and "Xin Shu"(BL15)can significantly improve the general behavioral signs of CHF rats and improve the cardiac function of CHF rats,which may play an autophagic effect similar to 3-MA by inhibiting cardiomyocyte over-autophagy to reduce myocardial injury. |
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