| In recent years,the incidence of heart failure after myocardial infarction and death rates continue to rise,cause serious damage to the human health.Ventricular remodeling after myocardial infarction is the important cause leading to the deterioration of cardiac function,the pathological process is mainly characterized by myocardial infarction area cell necrosis,the infarction area of myocardial cell apoptosis,hypertrophy and myocardial fibrosis.Serious damage to the heart of systolic and diastolic function,lead to the occurrence of heart failure.How to improve the ventricular remodeling after acute myocardial infarction,heart failure prevention,the major problem in myocardial infarction secondary prevention.Ventricular remodeling after myocardial infarction belong to the traditional Chinese medicine "obstruction,heartache,really painful",et cl.Traditional Chinese view is that the disease pathogenesis standard for this virtual to real,this virtual refers to qi deficiency of Yin and Yang,qi stagnation,blood stasis and phlegm obstruction.In clinical we often use WenYangYi Qi,yiqi huoxue,huoxue phlegm and other methods to promote blood circulation or remove blood stasis.But in combination with clinical observation,a lot of acute myocardial infarction patients have the symptoms such as chest pain,dry mouth and also bitter mouth,dry stool,yellow greasy coating on the tongue,pulse sliding and thermal image,and such as pure with promoting blood circulation to remove blood stasis effect is not ideal,as the improvement of living standards,people choice food spicy,such as life stress,and many other reasons,combined with modern medical research point of view,we think that toxic heat in the role of this kind of disease is very important,we should pay attention to clinical.Based on the TCM etiology and pathogenesis of ventricular remodeling after myocardial infarction,combined with clinical experience for many years,doctor Wang create yiqi huoxue jiedu prescription,in order to yiqi huoxue,qingrejiedu,its main composition of ginseng,salvia miltiorrhiza,rhizoma coptidis,radix paeoniae rubra,panax notoginseng,etc.The main goals of this paper is to observe "the cardiac function inhibition of ventricular remodeling"and "prevention and control of apoptosis",with yiqi huoxue decoction on myocardial infarction in the rat myocardial injury protective effect and mechanism research,proposed for yiqi huoxue jiedu advantages and characters of prevention and treatment of ventricular remodeling after myocardial infarction analysis to provide experimental basis.Objective:To observe the yiqi huoxue decoction on myocardial infarction in the rat cardiac function,myocardial infarction area and the influence of the ventricular remodeling,from the perspective of apoptosis as a breakthrough point,discusses the micrornas-21 level and target protein regulation of PTEN and its influence to the p38MAPK signaling pathways.Methods:128 healthy male Wistar rats,body quality(230±10g),were randomly divided into 4 groups:control group,model group,yiqi huoxue decoction group and captopril group.Rats by ligation of left anterior descending coronary artery method to establish myocardial infarction model,after 24 hours,the control group and model group was given 0.25%sodium carboxymethyl cellulose,yiqi huoxue jiedu party group was given yiqi huoxue decoction(1.19g/kg/d),captopril group was given captopril(30mg/kg/d).Three weeks postoperatively,echocardiography to detect left ventricular structure and function change,H-E staining to observe the myocardial pathological changes,the area of myocardial infarction and Masson staining test collagen volume fraction,biochemical analyzer to measure serum BNP and CRP levels,TUNEL staining detection infarction myocardial apoptosis of surrounding area,Western blot test district of myocardial infarction,the Bcl-2,Bax,Caspase-3,p38MAPK,p-p38MAPK and PTEN protein expression,qRT-PCR detection area of infarction rats rats left ventricular myocardial tissue expression of micrornas-21,TGF-?1,MMP-2 and MMP-9.Results:(1)Heart rate:There was no significant difference in HR between all groups(P>0.05).(2)EF and FS:?EF value:Compared with the sham operation group,the EF value of the model group was significantly lower in model group,the difference was statistically significant(P<0.01);Compared with the model group,the effect of Yiqi Huoxue Jiedu decoction group in EF was significantly higher than that of the model group(P<0.01).There was no significant difference between iqi Huoxue Jiedu decoction group and captopril group(P>0.05)).?FS value:Compared with the model group,the FS value of the model group was significantly lower than that of the sham operation group(P<0.01).Compared with the model group,the FS value was significantly increased(P<0.01).There was no significant difference between iqi Huoxue Jiedu decoction group and captopril group(P>0.05)).(3)LVIDd and LVIDs:?LVIDd:Compared with the sham group,the LVIDd of the model group was significantly higher than that of the sham group(P<0.05).Compared with the model group,the LVIDd of Yiqi Huoxuejiedu group was significantly decreased,the difference was statistically significant(P<0.05).There was no significant difference between iqi Huoxue Jiedu decoction group and captopril group(P>0.05)).?LVIDs:LVIDs were significantly increased in the model group compared with the sham operation group(P<0.05).There was no significant difference between the other groups and the sham operation group.(P<0.05).There was no significant difference between the two groups(P>0.05).Compared with the model group,the LVIDs were significantly lower in the Qiqihuoxuejujie group(P<0.05).There was no significant difference between iqi Huoxue Jiedu decoction group and captopril group(P>0.05)).(4)H-E staining:control group,no significant changes in myocardial tissue morphology neat myocardial cells,fibers,complete,broadly in line with a sarcomere length,muscular yarn clearer,muscle intracytoplasmic vacuoles degeneration,the nucleus dyeing is clear,no neutrophil infiltration;Model group compared to control group of myocardial tissue myocardial tissue distribution of a large number of inflammatory cells,did not see the complete myocardial cell morphology,myocardial horizontal stripes serious damage,muscle fiber fracture,dissolving and necrosis,myocardial cell interstitial hyperemia and edema,clearance increases,local inflammatory cell infiltration;Compared with model group,yiqi huoxue decoction group and captopril group improved degree of organization morphological changes,neutrophil infiltration decreased significantly,myocardial cell morphology is complete,muscle fibers arranged orderly,myocardial tissue hyperemia,swelling,alleviate.(5)Myocardial infarct size:compared with the model group,Yiqi Huoxue Jiedu recipe and captopril group can significantly reduce the infarct size,the difference is statistically significant(P<0.05).There was no significant difference between Yiqi Huoxue Jiedu recipe and captopril group(P>0.05).(6)Masson staining:under Masson staining showed that normal myocardial cells red,collagen fibers in blue.Control without collagen hyperplasia,myocardial cell order;Compared with the control group,model group rats myocardial cell edge area of infarction disordered arrangement,within the interstitial collagen fibers increased,blue segment myocardial bundles and part of the collagen fiber fusion,increase the degree of myocardial fibrosis.Compared with model group,yiqi huoxue decoction group and captopril group blue collagen fiber reduce,the degree of myocardial fibrosis.(7)The serum BNP and CRP content:?BNP:compared with the sham group,model group serum BNP content increased significantly,the difference was statistically significant(P<0.01);compared with the model group,Yiqihuoxuejiedu Decoction group and captopril group serum BNP content decreased significantly,the differences were statistically significant(P<0.05),no significant the difference between Yiqihuoxuejiedu Decoction group and captopril group(P>0.05).? CRP:compared with sham operation group,model group,Yiqihuoxuejiedu Decoction group and captopril group,serum CRP content increased significantly,the difference was statistically significant(P<0.01);compared with the model group,Yiqihuoxuejiedu Decoction group and captopril group,serum CRP content decreased significantly,the difference was statistically significant(P<0.05),no significant difference between Yiqihuoxuejiedu Decoction group and captopril group(P>0.05).(8)Collagen volume fraction:compared with sham operation group,model group,Yiqihuoxuejiedu Decoction group and captopril group collagen volume fraction increased significantly,the difference was statistically significant(P<0.01);compared with the model group,Yiqihuoxuejiedu Decoction group and captopril group Jiao Yuanrong score decreased significantly,the difference was statistically significant(P<0.01);There was no significant difference between iqi Huoxue Jiedu decoction group and captopril group(P>0.05).(9)TGF-?1,MMP-2 and MMP-9:?The expression of TGF-?1 in model group was significantly higher than that in sham operation group(P<0.05).The expression of TGF-?1 in TGF-?1 group was significantly higher than that in sham operation group(P<0.01).Compared with the model group,the levels of TGF-?1 in Yiqi Huoxue Jiedu group and captopril group were significantly lower than those in the model group(P<0.01)There was no significant difference in TGF-P,between the two groups(P>0.05).? The expression of MMP-2 in the model group was significantly higher than that in the sham group(P<0.01).Compared with the model group,the expression of MMP-2 in the model group was significantly higher than that in the model group(P<0.01).There was no significant difference in MMP-2 between Yiqi Huoxue Jiedu group and Captopril group(P>0.05).?The expression of MMP-9 in model group and captopril group was significantly higher than that in sham operation group(P<0.05).Compared with model group,the expression of MMP-9 in Yiqi Huoxue Jiedu group was significantly lower than that in model group(P<0.01).There was no significant difference in MMP-9 between Yiqi Huoxue Jiedu group and captopril group(P>0.05).(10)Apoptotic index:Compared with sham operation group,the positive rate of cardiomyocyte apoptosis in the model group,Yiqi Huoxue Jiedu group and captopril group was significantly higher than that in the sham operation group(P<0.05),and the difference was statistically significant(P<0.01).Compared with the model group,the positive rate of cardiomyocyte apoptosis in the peripheral region of Yiqi Huoxue Jiedu group and captopril group was significantly lower than that in the model group(P<0.01).There was no significant difference between Yiqi Huoxue Jiedu group and captopril group(P>0.05).(11)On the expression of Bax,caspase-3 and Bcl-2:? In Bax expression:Compared with sham operation group,the model group,Yiqi Huoxue Jiedu group and captopril group(P<0.05).Compared with the model group,the expression of pro-apoptotic protein Bax was decreased in the myocardium of the peripheral region of the infarcted group,and the expression of Bax was significantly higher than that of the model group(P<0.05).The expression of pro-apoptotic protein Bax in myocardium of captopril group was not significantly different(P>0.05).There was no significant difference between Yiqi Huoxue Jiedu group and captopril group(P>0.05).? In caspase-3 expression,the expression of caspase-3 in the myocardium of the model group was significantly higher than that in the sham operation group(P<0.05),and the difference was statistically significant(P<0.05).Compared with the model group,the expression of pro-apoptotic protein caspase-3 in the myocardium of the infarcted group and the captopril group was significantly lower than that in the model group(P<0.05);There was no significant difference between Yiqi Huoxue Jiedu group and captopril group(P>0.05).? In Bcl-2 expression,the expression of anti-apoptotic protein Bcl-2 in myocardium of model group and Yiqi Huoxue Jiedu group was significantly lower than that of sham-operated group(P<0.05),and the difference was statistically significant(P<0.05).Compared with the model group,the expression of anti-apoptotic protein Bcl-2 in the myocardium of the infarcted group and the captopril group was significantly higher than that of the model group(P<0.05).The difference was statistically significant(P<0.05).There was no significant difference in the expression of anti-apoptotic protein Bcl-2 between Yiqi Huoxue Jiedu group and captopril group(P>0.05).(12)p38MAPK and p-p38MAPK:(1)In the p38MAPK region:there was no significant difference in p38MAPK expression in all groups(P>0.05).(2)In the p-p38MAPK region:The expression of p-p38MAPK in the peripheral tissues was significantly different(P<0.05).Compared with the sham group,the expression of p-p38MAPK in the model group,Yiqi Huoxue Jiedu group and captopril group was significantly increased(P<0.05).Compared with the model group,the expression of p-p38MAPK in the myocardium of the infarcted group and the captopril group was significantly lower than that in the model group(P<0.05).There was no significant difference in the expression of p-p38MAPK protein between the YiQi Huoxue Huoxue Jiedu group and the captopril group(P>0.05).(13)Effects of PTEN expression:The expression of PTEN protein in the myocardium of the peripheral region of the rats in each group was significantly different(P<0.05)at 3 weeks after the operation.Compared with the sham group,the expression of PTEN protein in the peripheral region of the myocardial infarction group was significantly higher than that in the sham operation group(P<0.01).Compared with the model group,the expression of PTEN protein in the peripheral region of the infarcted group and the captopril group was significantly lower than that of the model group(P<0.01).There was no significant difference in the expression of PTEN protein between the two groups(P>0.05).There was no significant difference in the expression of PTEN between Yiqi Huoxue Jiedu group and captopril group(P>0.05).(14)miRNA-21:The expression of miRNA-21 in non-infarcted myocardium was significantly different(P<0.05)at three weeks after operation.Compared with the sham-operated group,the expression of miRNA-21 in the myocardial tissue of the model group was higher than that in the control group,the difference was not statistically significant.Compared with the model group,the expression of miRNA-21 in the myocardium of the patients with myocardial infarction was significantly higher than that in the model group(P<0.05).There was no significant difference in the expression of miRNA-21 in the myocardium of the peripheral region of the patients with myocardial infarction(P<0.05).Conclusion:(1)Based on Yiqihuoxue detoxification theory and disease combined with the guidance of the prescription side of the qi and blood toxins can play Qi and blood circulation,the role of heat detoxification,for coronary heart disease stasis heat poison mutual evidence.(2)Yiqi Huoxue Jiedu Decoction and captopril can reduce the myocardial infarct size of myocardial infarction rats,reduce the volume fraction of collagen,inhibit the expression of TGF-?1,MMP-2 and MMP-9,prevent myocardial fibrosis,increase myocardial infarction rats EF and FS values decreased,inhibition of LVIDd,LVIDs increased,improve myocardial function in rats with myocardial infarction,delayed ventricular remodeling,the combined effect was significantly better than captopril.(3)The expression of Bax and caspase-3,the expression of Bcl-2 and the expression of Bcl-2 in the peripheral region of the infarcted myocardium,can reduce the apoptosis of the cardiomyocytes.(4)Prevention and control of yiqi huoxue jiedu party after myocardial infarction,the mechanism of action of cell apoptosis may be related to increase of micrornas-21 level lowered its target protein in the expression of PTEN,which inhibit p38MAPK signaling pathway involved. |
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