Shenxian Shengmai Oral Liquid Mediates Gap Junction Protein To Improve Sinus Node Fibrosis

Purpose:To investigate the effect of Shen xian Shengmai Oral Liquid on the improvement of sinoatrial node fibrosis in mice,and the mechanism of Shen xian Shengmai Oral Liquid mediated gap junction protein 43 and 45(Cx43,Cx45)to improve sinus node fibrosisMaterial and Method:Fifty SP57 C57BL/6 mice were randomly divided into 5 groups:sham operation group(Sham group),sinus node fibrosis mode 1 group(Ang? group),and Shenxian Shengmai oral liquid high-dose group(SH group),Shenxian Shengmai oral liquid medium dose group(SM group),Shenxian Shengmai oral liquid low dose group(SL group).A small osmotic pump was implanted subcutaneously in the neck of the mice,and angiotensin was injected into the mice of the Ang? group,causing sinus node fibrosis damage in the mice of the Ang? group;the SH group,the SM group,and the SL group(Collectively referred to as the treatment group)mice were modeled using the above method,and the next day were administered with different doses by intragastric administration of 4W;the general state of the mice in each group was observed and recorded daily,using biological The signal acquisition and processing system monitored the sinoatrial node indicators of mice in each group on the 4th day,the 7th day after the operation,the 14th day after the operation,the 21st day after the operation,and the 28th day after the operation;The pathological changes of the sinoatrial node of the rats;MASSON staining was used to detect the degree of sinus node fibrosis in each group of mice;Western-blot and real-time fluorescent quantitative PCR(qRT-PCR)were used to detect the expression of Cx43,Cx45 protein and mRNAResults:1 General status of mice in each group:After subcutaneous injection of Ang? with a micro-osmotic pump,the general conditions of the mice in each group were observed daily.The mice in the Sham group were enlightened,the limbs were sensitive,the reaction was rapid,the shape was free,and the breath was normal.The fur is dense,smooth and shiny,and the body temperature and appetite are normal.In the Ang? group,weakness,loss of eyes,chills and warmth,sluggish movements,curled arches,dry fur standing upright and easy to fall off,edema of the back of the feet,back temperature and weight loss,loss of appetite,and oliguria.With the daily gavage treatment,the general state of the mice in the treatment group has improved.Among them,the general state of mind,fur,back temperature,and diet in the SH group has improved.The effect is the most significant.The improvement in the SL and SM groups is not as good.SH group2 Heart rate monitoring:The heart rate of the mice in the Sham group was normal,and the electrocardiogram showed sinus rhythm.Compared with the Sham group,the dim sum rate of the mice in the Ang? group decreased graduall y after surgery,and the difference was statistically significant(P<0.05),Monitor the electrocardiogram of mice in Ang? group,analyze the electrocardiogram at various times after surgery,and find that sinus bradycardia gradually increases;compared with Ang? group,the heart rate of mice in treatment group increased at all time points,and the differences were statistically significant.Significance(P<0.05),although the heart rate of the SL group and the SM group at each time point has improved,the effect is not as significant as that of the SH group.The ECG results of the SH group on the 28th day after surgery suggest sinusoidal electrocardiograms,and the observation of SL Diastolic electrocardiograms were found at various times after surgery in groups and SM groups,and sinus bradycardia gradually decreased;there was no significant difference in the improvement of various parameters of sinoatrial node in Ang ? mice between SL group and SM group,which was not statistically significant(P>0.05)3 HE staining:The sinus node tissues in the Sham group had normal cell structures and clear cell contours;the sinus node cells in the Ang? group had incomplete morphology,disordered arrangement,and obvious swelling;the nucleic ontracted,lysed,and degenerated,and a large amount of connective tissue was formed.A large number of vacuoles appeared;compared with the Ang? group,the degree of sinus node cell damage in the treatment group was reduced,the cell morphology was relatively complete,the arrangement was neat and orderly,the tissue congestion and swelling were improved,and occasionally the nuclear shrinkage and connective tissue were reduced.The improvement effect of sinus node tissue was the most obvious.The SL group and SM group had similar pathological improvement effect4 MASSON staining:no fibrosis was found in the sinoatrial node tissue of the Sham group;a large number of blue staining of the sinoatrial node area in the Ang? group,and severe sinus node fibrosis;Among them,the improvement of sinus node fibrosis in the SH group was significant,but there was no signif icant difference between the SL group and the SM group5 Western blot:Compared with the Sham group,the expressions of Cx43 and Cx45 in the Ang? group were inhibited,and the difference was statistically significant(P<0.05);the expressions of Cx43 and Cx45 in the treatment group were increased,and the difference was statistically significant.The significance was significant(P<0.05).The Cx43 and Cx45 proteins in the SH group were significantly increased,and the Cx43 and Cx45 protein expressions in the SL group and the SM group were not significantly different,which was not statis tically significant(P>0.05)6 qRT-PCR:Compared with the Sham group,the Cx43 and Cx45 gene expression in the Ang? group was significantly reduced,and the difference was statist ically significant(P<0.05);the Cx43 and Cx45 gene expression in the treatment group mice were increased,and the difference was statistically significant.Significance(P<0.05),the Cx43 and Cx45 genes of mice in the SH group increased more significantly,and the difference was statistically significant(P<0.05).There was no significant difference in the expression of Cx43 and Cx45 genes in the SL group and SM mice,which was not statistically significant.Significance(P>0.05)7 Immunofluorescence:Compared with the Sham group,the expression of Cx43 and Cx45 proteins in the Ang? group was significantly inhibited;the expression levels of Cx43 and Cx45 proteins in the treatment group were increased Compared with the SL group and the SH group,there was no significant difference in the expression of Cx43 and Cx45 proteins in miceconclusion:1 Shenxian Shengmai Oral Liquid can increase the heart rate and improve the fibrosis of sinus node tissue in mice with sinus node injury2 The mechanism of Shenxian Shengmai Oral Liquid to improve fibrosis of sinoatrial node tissue may be related to the breakdown of Cx43 and Cx45 expression.