| Purpose:In this study,the rat model of heart failure after myocardial infraction was established by ligation of the anterior descending cornary artery combine with exhaustiveswimming and diet reduction.After heart function detection and general condition determination,this rats were divided into groups and given the Bu Shen Huo Xue Compound,positive control drug Captopril and placebo for intervention.Observed Ca MK?,HDAC4 expression in myocardial tissue,to explore the Bu Shen Huo Xue compound can reduce the Ca MK? of myocardial tissue,the expression of HDAC4 content,improve the myocardial hypertrophy,provide new targets for the treatment of chronic heart failure of traditional Chinese medicine.Material and method:1.The construction of the rat model with chronic heart failure: the SPF 80 male rats,weight in250 ? 280 g,adaptability to feed a week later,were randomly selected 20 to do control,hang line without ligation,the rest 60 lines of left anterior descending coronary artery ligation,and after three days began to exhaustion swimming and reducing feed their construction of heart failure after myocardial infraction rats model,four weeks.After modeling,by echocardiography and was calculated EF ? 45%.Significant weight loss,partial hair loss,weight loss,mental fatigue,reduced diet and activity,audible and wheezing in severe cases were observed in the rats,which could be included in this study.2.Experimental grouping and drug administration: 39 surviving rats conforming to the model criteria were randomly divided into model group(13rats),traditional Chinese medicine group(13rats),western medicine group(13 rats),and sham operation group(19rats).In the traditional Chinese medicine group,the dosage of Bushen Huoxue Compound was15.75mg/(kg.d),Western medicine group was given Captopril tablets 1.125mg/(kg.d),model group and sham Operation groupe were given constant volume distilled water for intragastric administration,3ml each time,once a day.After 28 days of drug intervention in each group,echocardiography was detected again to observe the changes of cardiac function.3.Collection and detection of experimental specimens: After the end of medication,all rats w ere fasted from water for 12 hours,and were given intraperitoneal injection of 10% chloral hydrate(0.35ml/0.1kg)for anesthesia.Enzyme linked immunsrbent assay ELISA was used to measure serum BNP concentration in rats after anesthesia.Take heart tissue of rats,with immune histochemical methods to detect cardiac tissues Ca MK ? and the expression of HDAC4,HE staining to observe the myocardial pathology.Results:1.Injuries and injuries of rats during the experiment: coronary artery ligation was performed on rats in the sham operation group,20 rats were only sutured without ligation,1 rat died during the operation,and 19 rats remained.The rest 60 underwent coronary ligation,3 died of overdose of anesthesia before surgery,14 died of cardiac bleeding,airway obstruction,pneumothorax,arrhythmia and other causes during the operation,4 died during exhaustive swimming and diet.A total of 39 died in the end.According to random number table method,there were 13 rats in Chinese medicine group,13 rats in model group and 13 rats in western medicine group.During administration,2 patients died in the model group,1 patient died in the traditional Chinese medicine group,1 patient died in the western medicine group,and no death occurred in the sham operation group.2.General observation of the rats: after the successful modeling,the rats were observed to be significantly emasculated,with thinning hair,weight loss,mental fatigue,reduced diet and activity,and in severe cases,wheezing was audible.After medication intervention,the weight of rats in the traditional Chinese medicine group and the western medicine group basically returned to normal,their hair was shiny,their mental activities were good,their diet was OK,and no cough or asthma was observed.3.Compared with the sham operation group,the heart function of model group was significat-e higher LVID(ed)and LVID(es)(P<0.01),and EF and FS were significantly lower(P<0.01),with statistically significant differences between groups.Compared with sham operation g-roup,LVID(ed)and LVID(es)of western medicine group and Chinese medicine group were increased,while EF and FS were decreased,with statistical significance(P<0.01).However,compared with model group,LVID(ed)and LVID(es)decreased in the western medicine group,and Chinese medicine group,while EF and FS increased,with significant changes between groups,(P<0.01),indicating that the heart function of the two groups after drug intervention was significantly enhanced compared with the model group,but still could not reach the standard of sham operation.Compared with the traditional Chinese medicine group,there was on signification difference in each index between the western medicine group and the traditional Chinese medicine group.LVID(ed),LVID(es),EF and FS were all(P>0.05),indicating that the intervention degree of the western medicine group and the traditional Chinese medicine group on the heart function of rats with chronic heart failure had no statistical significance.4.Compared with the sham operation group,the heart weight index of the model group was s ignification increased,and the difference was statistically significant(P<0.01),suggesting that after modeling,the heart of the rats was enlarged,myocardial hypertrophy,and left ventricular mass was significantly increased,presenting the manifestations of heart failure,After drug treatment the index of TCM group and western medicine group was lower than that of model group and slightly higher than that of sham operation group,the difference was statistically significant(P<0.01).There was no significant difference between the Chinese medicine gro-up and the western medicine group(P>0.05),indicating that the two groups had the same efficacy.5.Compared with the sham operation group,the serum BNP expression in the model group was significantly increased(P<0.01),and there was a significant difference between the two groups.After two drugs intervention,BNP concentration decreased(compared with model g roup,P<0.01),but there was still a difference compared with sham group(P<0.01).There w as no significant difference between the western medicine group and the traditional Chinese medicine group(P > 0.05).6.The myocardial tissue of each group was observed under light microscope.The muscle fibers in the longitudinal section of the myocardium of rats in the sham operation group were slender and long strips,arranged neatly,and branches were connected into a network.The nucleus is elliptic and bright in the center of the cell.There is a small amount of connective tissue.Between the myocardial fibers(see figure);In the model group,the myocardial fibers were disoreder and unclear with wavy changes,and the myofibrils were not clear.Some of the rhabdoid muscles disappeared,the nuclei were enlarged,and some of the nuclei were pyknosis.Increased connective tissue in the myocardium(see image).After intervention,both the Chinese medincine group and the western medicine group were improved,with irregular arrangement of myocardial fibers but most of them were normal and relatively compact,a few rhabdomous muscles disappeared,less connective tissue between myocardial fibers and a small amount of nuclear pyknosis,which was significantly better than that in the model group.7.After 4 weeks compared with control group,model group Ca MK?average grey value incr-ease,the difference was statistically significant(P<0.01);Compared with model group,Ca MK?average grey value in traditional Chinese medicine and western medicine in the two groups to reduce,the difference was statistically significant(P<0.01);Compared with the western medicine group,Ca MK ? average grey value in the expression of Chinese traditional medicine group were similar,no statistical difference(P>0.05).Compared with the sham operation group,the expression level of HDAC4 in the myocaridal of the model group after 4 weeks of administration was significantly increased,with statistical significance(P <0.01).Compared with the model group,he expression level of HDAC4 in the myocardium of the TCM group and the western medicine group was significantly decreased which was comparable and significant(P<0.01).Compared with the western medicine group,the expression level of HDAC4 in the myocardium of the Chinese medicine group was not significantly different,which was not statistically significant(P > 0.05).Conclusion:1.By comparing the data of each group,it is proved that Bushen Huoxue Compound can improve the heart function of rats,regulate the serum BNP level of rats,relieve the symptoms of heart failure,and achieve the effect of treating chronic heart failure.2.By comparing the experimental data,proving that kidney invigorate the compound can be cut in the myocardial tissue of Ca MK ?,the expression of HDAC4,improve myocardial hypertrophy,delay the ventricular remodeling.3.Through this experiment,it is proved that Bushen Huoxue Compound is safe and effective in the treatment of chronic heart failure,and its therapeutic effect is comparable to that of Captopril. |
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