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Effects Of Monodoxin On Ventricular Remodeling In Rats After Myocardial Infarction

Posted on:2005-12-31Degree:MasterType:Thesis
Country:ChinaCandidate:H T WangFull Text:PDF
GTID:2144360122991023Subject:Internal Medicine
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PrefaceAcute myocardial infarction (AMI) is a serious disease that treatens human health. How to improve cardiac function after AMI and improve long - term prognosis are catching more and more attention. One of the most important mechanisms in relation to deterioration of heart function after AMI is ventricular remodeling (VRM ).Monodoxin is one kind of tetracycline. It has been establiashed that mono-doxin also is a broad - spectrum matrix metalloproteinases inhibitor, preventing internal proliferation and formation of aneurysm after arterial injury .The purpose of this study is to discuss the effects of monodoxin on myocardial interstitium after AMI by establishing rat acute myocardial infarction model and observing the effects of monodoxin on MMP - 9 so as to speculate its function on ventricular remodeling .Materials and methodsForty - five healthy female Wistar rats were randomly allocated into three groups, each of which had fifteen rats. In experimental group and control group, a left thoracotomy was performed in the fourth intercostals space, and the pericardium was opened with the ligation of the left coronary artery. All experimental rats received monodoxin solution 10 mg/kg/d in one milliliter saline by intra-gastric administration. In control group, rats received the same dose saline. In sham - operated group, rats were treated in the same way as previously described except for coronary ligation. Seven days after surgery, all rats were killed. The hearts were excised and immersed into 4 % parafonnaldehyde in phos-phate - buffered saline for more than 24 hours. Subsequently, the hearts were embedded in paraffin. Transverse serial sections 5um thick were cut. HE staining observed the changes of left ventricular structure. MMP - 9 was examined with immunohistochemical method. All the results were scanned and semi -quantitatively analyzed by computer. SPSS11.0 software was adopted to examine all values.Results1. Fifteen of forty - five rats were dead, six in experimental group, seven in control group two in sham - operated group, including early death within 24 hours. Operative mortality of the surgical procedure was 33.3 %.2. Morphometric analysis with HE staining. Left coronary artery occlusion produced myocardial infarction. IN experimental and control group, infarction was observed, with myocardial fibre dissolving and broken. Pathological changes in control group were more serious than those in experimental group. No infarction was observed in sham - operated group. The experimental and control group showed significant increases in left ventricular cavity area, free wall thickness. The infracted zone was thinner (p < 0. 05 ). The changes of monodoxin treated rats were less than those of control group (p < 0.05).3. Staining of MMP - 9 in myocardium with immunohistochemical method. The expression of MMP - 9 was increased both in experimental and control group. In control group, the expression of MMP -9 is the most significant. Moreover , control group grey values were the lowest among all of the three groups (MMP-9, vs experimental group, p < 0.05; vs sham - operated group,p < 0.05)DiscussionLeft ventricular remodeling after AMI is defined as alterations in shape and dimensions of global ventricle. Remodeling process consists of infarct expansion and ventricular dilatation, leading to ventricular morphological changes. In thepast, ventricular remodeling was contributed to the changes of cardiomyocytes , but now ,it has been realized that alterations of myocardial extracellular matrix play an important role in remodeling process. The alterations of myocardial extracellular matrix after AMI mainly comprise collagen degeneration and resynthe-sis, redistribution and fibrosis.Matrix metalloproteinases are a family of zinc - dependent enzymes, in charge of degeneration of extracellular matrix. Matrix metalloproteinases can be classed into four groups . The first group is collagenases, such as MMP - 1, MMP - 3, function of which is to degenerate collagen in...
Keywords/Search Tags:Monodoxion, Myocardial infarction, ventricular remodeling, Matrix metalloprotemases
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