| ObjectiveThe aim of this study was to investigate the therapeutic effect of Huo-xue Jiang-tang decoction on diabetic cardiomyopathy and its regulation on the signal transduction pathway of neuromodulin 1/epidermal growth factor(NRG1/ErbB),try to explore its mechanism from the molecular level and provide theoretical basis for the treatment of diabetic cardiomyopathy.Methods1.In clinical study,50 patients with diagnostic criteria of diabetic cardiomyopathy and syndrome of qi deficiency and blood stasis were randomly-divided into treatment group(n = 25)and control group(n = 25).The two groups were given the same basic treatment,including diabetes diet health education,blood glucose control.The control group was treated with basic treatment and benazepri110 mgPoQD;On the basis of the control group,the treatment group was treated with the Huo-xue-Jiang-tang Decoction,and the decoction was decocted 1 dose a day,which was divided into 2 times,1 month for a course of treatment.Before and after the treatment,the total effective rate and TCM syndrome scores were observed,the biochemical indexes of FPG,2hPG,FINS,HbA1C,TC,TG,the Oxidative stress index of SOD,T-AOC,GSH-PX,the cardiac function index of LVESD.LVEDD.LVEF.6MWT and the inflammatory index of TNF-a,IL-6 were determined and compared after treatment;2.In basic experiment,male SD rats were fed with high glucose and high fat diet for 4 weeks,then treated with low dose of STZ(30mg/kg)to establish the rat model of diabetes,control group was established meanwhile.The model rats were randomly divided into model group,low dosegroup of Huo-xue-Jiang-tang Decoction and high dose of Huo-xue-Jiang-tang Decoction.Low dosegroup were treated with Huo-xue-Jiang-tang Decoction(5g/kg/d)and high dosegroup were treated with Huo-xue-Jiang-tang Decoction(lOg/kg/d).After eight weeks,fastingplasma glucose,triglyceride,total cholesterol,SOD,GSH-PxAndMDA weredetermined.Echocardiographyexamination were performed,myocardialtissue HE staining and TUNEL apoptosis analysis were operated.Furthermore,using Q-PCR and Western blot to detect the gene and protein expression level of NRG1?ErbB2?AKT?Bax?Bcl-2.ResultClinical Part(1)After the treatment,the total effective rate of the treatment group(840%)was significantly higher than that of the control group(68%)(P<0.05).TCM syndrome integral comparison,after treatment two groups TCM symptom scores of patients were significantly reduced(P<0.05),the difference between the prior and post treatment of two groups,the treatment group was significantly better than the control group(P<0.01).(2)After the treatment,thelevel of FPG,2hPG,FINS,HbAlC,TCandTG significantly decreased in the two groups,and the treatment group was significantly lower than the control group,the difference was statistically significant(P<0.05).(3)Two groups of patients after treatment of SOD,T-AOC and GSH-PX levels were significantly higher than those in the same group before treatment;the differences were statistically significant(P<O.05);compared with the control group,the level of plasma SOD,T-AOC and GSH-PX of treatment group significantly increased,the differences were statistically significant(P<0.05).(4)After the treatment,two groups of cardiac function indexes LVESD,LVEDD,LVEF,6MWT were significantly improved(P<0.05).Compared with prior treatment,theLVESD,LVEDD of treatment group decreased significantly,and the degree of decline was significantly lower than that of the control group(P<0.05);LVEF,6MWT significantly increased,and thedegree of increase was significantly higher than that of the control group(P<0.05).(5)After the treatment,two groups of TNF-a and IL-6 were significantly decreased(P<0.05),and the control group was better than the control group,the difference was statistically significant(P<0.05).Animal Experiment Part(1)Compared with the control group,the fasting blood glucose of rats in the model group significantly increased(P<0.05).Compared with the model group,the content of fasting blood glucose decreased after the treatment in Huoxue Jiangtang Decoction with low dosage or Huo-xue-Jiang-tang Decoction with high dosage(P<0.05).Compared with the control group,the insulin in the model group was significantly higher than that in the control group(P<0.05).Compared with the modle group,the serum insulin level of the rats in Huoxue Jiangtang Decoction groups were significantly decreased(P<0.05).(2)Compared with the control group,total cholesterol and triglyceride in the model group significantly increased(P<0.05);Huo-xue-Jiang-tang Decoction groups treatment reduce the content of total cholesterol and triglyceride,compared with the model group,there were significant differences(P<0.05).(3)Compared with the control group,myocardial SOD GSH-Px activity in model group decreased significantly(P<0.05),while compared with model group,Huoxue Jiangtang Decoction groups treatment could make SOD,GSH-Px activity in the myocardial tissue of DCM rats increased significantly(P<0.05).Compared with the control group,the content of MDA in the myocardial tissue in the model group was significantly higher.Compared with the model group,the content of MDA in the myocardial tissue of DCM rats in Huo-xue-Jiang-tang Decoction groups were significantly lower(P<0.05).(4)Compared with the control group,the LVPWT.LVDD and LVDS in model group increased and the LVEF decreased in the model group at 12th week,and the difference was statistically significant(P<0.05).The LVPWT?LVDD?LVDS and LVEF in Huo-xue-Jiang-tang Decoction groups were significantly improved compared with the model group at 12th week,the difference was statistically significant(P<0.05).(5)The control group of myocardial cells arranged closely,neatly and were visibleafter nuclear staining;myocardial cell of model group were disorder,cell hypertrophy and deformation,nuclear staining deep,obvious interstitial fibrosis and inflammatory cell infiltration;Myocardial cells of Huoxue Jiangtang Decoction groups arranged a little chaotic,cell morphology,compared with control group,was roughly the same and clear nuclear staining.In the model group TUNEL staining positive cells,compared with the control group,increased significantly(P<0.05);Compared with model group,number of positive staining cells in Huo-xue-Jiang-tang Decoction groups decreased significantly(P<0.05).(6)The expression level of NRG1,p-ErbB2,p-AKT,Bax,Bcl-2 protein in the model group detected by Western blot was showing a downward trend,while the expression of Bax showed a rising trend,compared with the control group,there were significant differences(P<0.05);Compared with the model group,the NRG1?p-ErbB2,p-AKT and Bcl-2 expression in Huo-xue-Jiang-tang Decoction groups significantly increased,while the expression of Bax decreased,there were significant differences(P<0.05),the expression is dependent with the dose.(7)mRNA expression levelof NRG1,ErbB2,AKT,Bax,Bcl-2 detected by Fluorescence quantitative PCR showed a downward trend in the model group,while the expression of Bax gene showed a rising trend,compared with the control group,there were significant differences(P<0.05);mRNA expression level of ErbB2,AKT,Bcl-2 in Huo-xue-Jiang-tang Decoction groups,compared with the model group,significantly increased,while mRNA expression level of Bax decreased significantly,there were significant differences(P<0.05),the expression is dependent with the dose.Conclusion1.Qi and yin deficiency is the basic pathogenesis of diabetic cardiomyopathy,blood stasis is an important pathogenic factor of diabetic cardiomyopathy.Therefore,theHuo-xue-Jiang-tang Decoction which effect on supplementing qi,nourishing yin,promoting blood circulation and removing blood stasis is effective on treating diabetic cardiomyopathy patients.2.Huo-xue-Jiang-tang Decoction can improve the glucose and lipid metabolism of diabetic cardiomyopathy,improve the oxidative stress state of patients,reduce the levels of inflammatory factors TNF-a and IL-6,improve the level of cardiac function and prognosis.3.Huo-xue-Jiang-tang decoction can significantly increase the level of SOD,GSH-Px activity,down regulate the level of MDA,improve the cardiac function indexes of LVDD,LVDS,LVPWT and LVEF.The mechanism may be related with inhibiting the oxidative stress of myocardial cells,regulating the expression of Bax and Bcl-2 protein through NRG1/ErbB pathway,reducing myocardial apoptosis andimproving mitochondrial oxidativestress,correcting endothelial dysfunction,so that improving microcirculation. |
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