| Purpose: By observing the effect of Zhenwu Decoction on ventricular remodeling and cardiac function related indexes in mice with DCM,the mechanism of Zhenwu Decoction in the treatment of DCM was discussed.Provide scientific experimental data and theoretical basis for the clinical application of Zhenwu decoction in the treatment of DCM.Material and method: In this study,60 mice with SPF grade male c Tn TR141 W transgenic dilated cardiomyopathy and 15 SPF male C57BL/6J mice were studied.All are 4 months old and the body mass is 20±3g.Intervention drug Zhenwu decoction: According to " Treatise on Cold Pathogenic Diseases," the original prescription drug dose and compatibility ratio of prescription: Aconite 15 g,Atractylodes 30 g,Poria 45 g,Chinese herbaceous peony 45 g,ginger 45 g.The concentrated solution was prepared by the preparation room of the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine.The comparator drug is captopril,an effective drug currently recognized for the treatment of dilated cardiomyopathy.60 mice of SPF grade male c Tn TR141 W transgenic dilated cardiomyopathy were randomly divided into high-dose Zhenwu decoction group,Zhenwu decoction medium-dose group,positive drug control group(captopril group),and model control group,with 15 in each group.15 male C57BL/6J mice of grade SPF were in the blank control group.Zhenwu decoction drug treatment group,given Zhenwu decoction gavage.The middle dose is equivalent to 18.2g/(kg·d)of crude drug,and the high dose is equivalent to 36.4g/(kg·d)of crude drug.They are made into 0.6ml solution,and are given twice a day,0.3ml each time.Medication for 1 month.The positive drug blank group was given captopril gavage,the dose was 10mg/(kg.D),the 0.6ml solution was made,each time 0.3ml,2 times a day by gavage,continuous medication for 1 months.The model blank group and the blank blank group were given normal saline for gastric perfusion,2 times a day for 1 months at a time of 0.3ml.After the end of the experiment,the eyeballs were taken for blood sampling and serum samples were prepared and stored frozen for use.Experiment 1: the value of ST2,ET and ANG in the serum of mice was measured by ELISA.The values of LVESD,LVEDD,LVEF and LVFS were detected by color Doppler ultrasound of small animals.Experiment 2:Real-time fluorescent quantitative PCR was used to detect the expression of Bax and Bcl-2 m RNA in myocardial tissue.The expression of Bax and Bcl-2 protein in myocardial tissue of mice was detected by Western-blot.Statistical Analysis: SPSS 19.0 statistical software was used for statistical analysis.The data was expressed as the mean plus/minus standard deviation(?x±s).One-way analysis of variance was used for comparison between groups.The data was tested for normality and homogeneity of variance and was in accordance with normal distribution and variance.P<0.05 was a significant difference in results,with statistical significance.Results: 1.Comparison of Color Doppler Measurements in Each Group of Mice Compared with the blank group,the left ventricular ejection fraction of all the mice in each group decreased significantly,and the difference was statistically significant(P<0.05).Compared with the model group,the left ventricular ejection fraction of the mice in each drug treatment group increased significantly,and the difference was statistically significant(P<0.05).Compared with the blank group,the left ventricular end diameter of the left ventricle increased significantly in all groups,and the difference was statistically significant(P<0.05).Compared with the model group,the left ventricular diastolic diameter of the mice in each drug treatment group decreased significantly,and the difference was statistically significant(P<0.05).Compared with the blank group,the left ventricular end systolic diameter increased significantly in all groups,and the difference was statistically significant(P<0.05).Compared with the model group,the left ventricular end systolic diameter of the mice in each drug treatment group decreased significantly,and the difference was statistically significant(P<0.05).There was no significant difference in the above three indicators between the drug treatment groups(P>0.05).Compared with the blank group,the short axis shortening rate of left ventricle in each group was significantly reduced,and the difference was statistically significant(P<0.05).Compared with the model group,the short axis shortening rate of the left ventricle in each drug treatment group was significantly increased,and the difference was statistically significant(P<0.05).Compared with the medium-dose group,the short-axis shortening rate of left ventricle in mice with high-dose Chinese herbs was significantly increased,and the difference was statistically significant(P<0.05).There was no significant difference between the Chinese medicine medium-dose group and the high-dose group compared with the western medicine group(P>0.05).2.Comparison of serum ET level in mice of each group Compared with the blank group,the levels of serum ET in all the other groups were significantly increased,and the difference was statistically significant(P<0.01).Compared with the model group,the level of ET in the high-dose group was significantly lower than that in the model group(P<0.05).The ET level in the western medicine group and the traditional Chinese medicine medium dose group decreased,and the difference was not statistically significant(P>0.05).There was no significant difference in the level of ET in the drug treatment group(P>0.05).Compared with the low dose group of traditional Chinese medicine,the level of ET had a tendency to decrease.3.Comparison of serum ST-2 levels of mice in each group Compared with the blank group,the level of soluble ST2 in the model group increased significantly,the difference was statistically significant(P<0.01).Compared with the model group,the level of soluble ST2 in the western medicine group and the high-dose Chinese medicine group was significantly reduced,and the difference was statistically significant(P<0.01).Compared with the western medicine group,the level of soluble ST2 in the medium-dose group was significantly increased(P<0.01),and the level of soluble ST2 in the high-dose group was significantly decreased(P<0.01).Compared with the medium-dose Chinese medicine group,the level of soluble ST2 in the high-dose Chinese medicine group was significantly reduced,and the difference was statistically significant(P<0.01).4.Comparison of serum MMP-1 level in mice of each group Compared with the blank group,the level of MMP-1 in the model group was significantly higher and the difference was statistically significant(P<0.01).Compared with the model group,the levels of MMP-1 in the high-dose group and the western medicine group were significantly decreased(P<0.01);the levels of MMP-1 in the middle-dose group were significantly lower,and the difference was statistically significant(P<0.05).).There was no significant difference in the level of MMP-1 between the drug treatment groups(P>0.05).The high-dose Chinese medicine group and the traditional Chinese medicine low-dose group,the level of MMP-1 decreased.5.Comparison of expression level of Bcl-2 m RNA in myocardial tissue of each group Compared with the blank group,the expression of Bcl-2 m RNA in model group(P<0.01),western medicine group(P<0.05),high dose Chinese medicine group(P<0.01),Chinese medicine medium dose group(P<0.01)was significantly decreased,and the difference was statistically significant.Compared with the model group,the expression of Bcl-2 m RNA in western medicine group increased significantly,the difference was statistically significant(P<0.01).The expression of Bcl-2 m RNA in high dose group increased significantly,the difference was statistically significant(P<0.05).The expression of Bcl-2 m RNA in Chinese medicine medium dose group was increased,the difference was not statistically significant(P>0.05).There was no significant difference between the high dose group of traditional Chinese medicine and the western medicine group and the medium dose group(P>0.05).Compared with the western medicine group,the expression of Bcl-2 m RNA decreased in the medium dose group,and the difference was statistically significant(P<0.05).6.Comparison of expression level of Bax m RNA in myocardial tissue of each group Compared with the blank group,the expression of Bax m RNA in the model group increased significantly,the difference was statistically significant(P<0.05).Compared with the blank group,the Bax m RNA expression increased in all drug treatment groups,and the difference was not statistically significant(P>0.05).Compared with the model group,the expression of Bax m RNA in the high-dose group was significantly lower than that in the model group(P<0.05).The expression of Bax m RNA in the western medicine group and the traditional Chinese medicine medium dose group were lower than that in the model group,and the difference was not statistically significant(P>0.05).The expression of Bax m RNA in high dose group of Chinese medicine was lower than that in western medicine group and medium dose group,and the difference was not statistically significant(P>0.05).Compared with the western medicine group,the expression of Bax m RNA in the medium dose group was lower than that in the western medicine group,and the difference was not statistically significant(P>0.05).7.Comparison of the expression level of Bcl-2 protein in each group of myocardium Compared with the blank group,the expression of Bcl-2 protein in each group was significantly decreased,and the difference was statistically significant(P<0.01).Compared with the model group,the expression of Bcl-2 protein in the western medicine group and the high-dose Chinese medicine group was significantly increased(P<0.05);the Bcl-2 protein expression in the Chinese medicine medium-dose group had a tendency to increase,the difference was not statistical Significance(P>0.05).Compared with the western medicine group,the expression of Bcl-2 protein in the high dose group of traditional Chinese medicine has a tendency to increase,the difference was not statistically significant(P>0.05);the expression of Bcl-2 protein in the medium dose group has a decreasing trend,the difference was not statistically significant(P>0.05).Compared with the medium-dose group,the expression of Bcl-2 protein in the high-dose group of traditional Chinese medicine has an increasing trend,the difference was not statistically significant(P>0.05).8.Comparison of Bax Protein Expression Levels in Different Groups of Myocardial Tissues Compared with the blank group,the expression of Bax protein in the model group increased significantly,the difference was statistically significant(P<0.01);western medicine group,the expression of Bax protein in dose group increased significantly,the difference was statistically significant(P<0.01);high dose of Chinese medicine group the expression of Bax protein increased,the difference was not statistically significant(P>0.05).Compared with the model group,the expression of Bax protein in each drug treatment group decreased significantly(P<0.01).Compared with the western medicine group,the expression of Bax protein in the high-dose group was significantly lower than that in the western medicine group(P<0.01),and the expression of Bax protein in the middle dose group had a decreasing trend,and the difference was not statistically significant(P<0.05).Compared with the medium dose group,the expression of Bax protein in the high dose group of traditional Chinese medicine decreased,the difference was not statistically significant(P>0.05).Conclusion: 1.Zhenwu decoction can significantly increase the EF and FS values of dilated cardiomyopathy mice,reduce the LVEDD and LVESD values,improve ventricular remodeling and improve cardiac function in dilated cardiomyopathy mice.2.Zhenwu Decoction can reduce the serum ET level,soluble ST2 level and MMP-1 level in the mice with DCM to inhibit myocardial cell remodeling,reduce the activation of RAAS system,inhibit myocardial fibrosis and inhibit the remodeling of extracellular matrix(ECM)of myocardium,thus improve ventricular remodeling and then improve cardiac function.3.Zhenwu decoction can upregulate the expression of Bcl-2 gene and protein in dilated cardiomyopathy mice and down-regulate Bax gene and protein expression to interfere with apoptosis regulatory factors,inhibit cardiomyocyte apoptosis,thereby improve ventricular remodeling,and then improve cardiac function. |
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