| Background: The majority of etiology of acute myocardial infarction(AMI)is atherosclerotic plaque instability and rupture and thrombus formation in coronary artery which interrupt blood flow,there are a large number of inflammatory reactions in the onset of the disease,platelet adhesion reaction activates prethrombotic state and vasoactive factors take part in this.Although the patients were treated with antithrombotic drugs or percutaneous coronary intervention to have myocardial reperfusion,intracellular molecules are damaged or dead cells release inflammatory factors,inflammatory response occurs,which plays an important role in myocardial remodeling and fibrosis.One of the key factors in the treatment of coronary heart disease is to reduce the unstable plaque and to inhibit the inflammatory reaction,however,there are not yet accepted drugs and other medical treatments.Early reports indicate that In addition to lipid-lowering effect,atorvastatin also play other diversified role in the cardiovascular system,such as anti-inflammatory,antioxidant,antifibrosis,but whether atorvastatin can affect inflammation and fibrosis in rats with acute myocardial infarction,and whether affect heart function and hemodynamic parameters,whether through regulating TGF-beta-smad pathway and Notch1 pathway signaling pathways still unknown.In addition,the changes of plasma inflammatory factor Galectin-3 in patients with coronary heart disease are unknown.Purpose: 1.To evaluate the changes of cardiac function after acute myocardial infarction in rats and the effect of atorvastatin/Losartan potassium on inflammatory factor TNF-alpha and IL-1 beta in rats after myocardial infarction for 5 days;2.To observe the effects of atorvastatin/Losartan potassium on cardiac function and hemodynamics of myocardial infarction rats after 14 days,the changes of myocardial extracellular matrix metalloproteinase MMP2,MMP9 and the inhibitor expression of TIMP2 and the changes of heart function markers BNP;3.28 days after rat AMI model,to observe the effects of atorvastatin/Losartan potassium therapy on cardiac function and hemodynamics,myocardial Collagen I,Collagen III,Notch1,TGF-beta 1,Smad2,Smad7,and the expression of Galectin-3 protein and BNP changes;whether atorvastatin / losartan potassium inhibited myocarditis inflammation and fibrosis in AMI rats through notch1-TGF-beta-smad signaling pathway;4.To observe the effects of atorvastatin / losartan potassium on the structure of myocardial cells and myocardial collagen fibers in AMI rats 14 days or 28 days later;5.clinical trials: in patients with coronary heart disease included stable angina pectoris(SAP),unstable angina pectoris(UAP)and AMI: to observe inflammatory factors Galectin-3 changes and the correlation with severity of the disease,Galectin-3 lever in atrial fibrillation patients before and after radiofrequency ablation,and the Galectin-3 changes of 80 mg atorvastatin treatment on patients with acute myocardial infarction before and after short-term treatmentMethod: 1?The rats were divided into four groups: control group(sham): simple isolate anterior descending without ligation;AMI group(model): simple ligation of the anterior descending coronary artery,no drug treatment after modeling;atorvastatin group: anterior descending coronary artery ligation + Lipitor(10mg/kq/d)treatment;losartan group: anterior descending coronary artery ligation + losartan(5mg/kq/d),except the rats in the normal group,EF of the rest rat groups selected were less than 50%,changes of heart function and hemodynamics of rats in each group were evaluated after AMI modeling 14 days or 28 days later,and observe the change process of development of myocardial cell inflammation and fibrosis in AMI rats.2?Elisa method was used to observe the changes of inflammatory factor TNFalpha,IL-1 beta in the 5 days after the onset of AMI modeling and BNP changes14 days or 28 days after AMI modeling;3?Using biological Q-PCR?Western blot technology and / or immunohistochemistry method to observe inflammatory factor TNF-alpha,IL-1 beta,Galectin-3,myocardial Collagen?,Collagen III,matrix metalloproteinase MMP2,MMP9 and signaling pathway protein TGF-beta 1,Notch1,Smad2,Smad7 of the different groups rats after modeling;4?HE staining and MASSON staining were used to observe the changes of myocardial cell structure and myocardial collagen fibers in different groups rats 14 and 28 days after AMI modeling;5?Clinical trials:to observe Galectin-3 changes by Elisa method in patients with coronary heart disease and Galectin-3 changes in atrial fibrillation patients before and after radiofrequency ablation(RFCA),80 mg atorvastatin were given to AMI patients before PCI,and to observe high dose atorvastatin treatment on the changes of Galectin-3 before and after PCI in AMI patients;to observe Correlation between plasma Galectin-3 level and LVEF in patients with coronary heart disease.Result:1?Cardiac function of rats were significantly decreased on the first day after acute myocardial infarction,EF,FS value is lower than that of control group;5 days after AMI rats modeling,the levels of plasma inflammatory factor TNF-alpha and IL-1 beta increased,and which decreased significantly after atorvastatin / losartan potassium treatment(P < 0.05);2?Cardiac function of rats were increased in atorvastatin group or losartan group in 14 days after modeling AMI rats,the hemodynamic parameters dp/dt Max and dp/dt Min were significantly improved(p<0.05);Q-PCR and / or Western Blot and / or immunohistochemistry results showed that atorvastatin / losartan potassium inhibited the expression of MMP2,MMP9,TNF-alpha,IL-1 beta protein and increased the expression of TIMP2 protein(p<0.05;14 days after modeling,the plasma level of cardiac function marker BNP was increased,and decreased(P < 0.05)in atorvastatin or losartan group;3?Cardiac function of rats were increased in atorvastatin group or losartan group in 28 days after modeling AMI rats,the hemodynamic parameters dp/dt Max and dp/dt Min were significantly improved(p<0.05);Q-PCR and / or Western Blot results showed that atorvastatin / losartan potassium inhibited the expression of collagen I,III,Notch1,TGF-?1,Smad2,Galectin-3 protein and increased the expression of Smad7 protein;28 days after modeling,the plasma level of cardiac function marker BNP was increased,and decreased in atorvastatin or losartan group(P < 0.05);4?14 days and 28 days after AMI modeling rats,myocardial cell structure disorder were improved,inflammatory cells decreased,myocardial collagen fibrous tissue reduced in Lipitor or losartan treatment group;5?Clinical trials:Galectin-3 level of AMI group was higher than that of UAP group,Galectin-3 level of UAP group was higher than that of SAP group(p<0.05),there were statistically significant differences between groups;Galectin-3 level of multivessel coronary disease group was higher than that of single lesion group(p<0.05);atrial fibrillation(AF)patients had RFCA,AF was conversed to sinus rhythm after RFCA and Galectin-3 lever decreased,there was no significant differences;AMI patients took 80 mg Atorvastatin before PCI,which could reduce the plasma Galectin-3 level,but there was no difference before and after PCI;there was negative correlation with EF value(r =-0.405,p<0.05).Conclusion: 1? After AMI modeling in rats,a series of inflammation and fibrosis reaction appeard,Inflammatory factor TNF-alpha,IL-1 beta,Galectin-3 increased and fibrosis factor MMP2,MMP9,Collagen I,Collagen III elevated,ventricular remodeled,cardiac function is damaged to some degrees,and atorvastatin or losartan may inhibit myocardial inflammation and fibrosis through notch1-TGF-beta-smads pathway,reduce inflammation and fibrosis expression,reduce myocardial remodeling,improve the heart function and hemodynamics;2?Atorvastatin or losartan can improve myocardial cell necrosis and structural disorder of AMI rats,and less myocardial collagen fiber range3?Clinical trials :The content of Galectin-3 was correlated with the severity of myocardial ischemia,with the aggravation of myocardial ischemia,the content of Galectin-3 increased gradually;Galectin-3 is negatively correlated with cardiac ejection fraction;4?Galectin-3 is a kind of inflammatory and fibrosis factor,which is correlated with the degree of inflammation and fibrosis,elevated Galectin-3 levels of AF patients is was associated with atrial fibrosis,Galectin-3 level after RFCA declined,but there is no difference before and after RFCA;atorvastatin reduces Galectin-3 level of AMI patients after PCI,but no difference before and after PCI. |
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