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Effects Of Diltiazem On The Expression Of Matrix Metalloproteinases In Rats After Myocardial Infarction

Posted on:2004-07-30Degree:MasterType:Thesis
Country:ChinaCandidate:Y L ZhaoFull Text:PDF
GTID:2144360092996061Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Acute myocardial infarction ( AMI) is a serious disease that threatens human health. The problems about treating AMI and its complications are hot topics in the medical fields. Left ventricular re-modeling ( LVRM ) is a common phenomenon after AMI, which is closely related to the prognosis.Diltiazem is a kind of short - acting benzothiazepines calcium channel antagonists (CCAs) , which has been used in recent years. It has many effects such as increasing coronary flow and decreasing blood pressure by blocking L - type Ca2+ - channel in the cell membrane. However, few people investigate whether it could reduce LVRM after myocardial infarction.The purpose of this study was to discuss the effects of diltiazem on myocardial interstitium after AMI by setting up rat myocardial in-farction model and observing the effects of diltiazem on MMP - 2, MMP - 9 and collagen so that we could speculate its function on LVRM.Materials and methodsForty - five healthy male Wistar rats were randomly allocated intothree groups, each of which had fifteen rats. In experimental group and control group, a left thoracotomy was performed in the fourth in-tercostals space, and the pericardium was opened with the ligation of the left coronary artery. After forty - five minutes, the myocardium was reperfused by cutting the ligature around the left coronary artery. All experimental rats received diltiazem solution 3mg ?kg-1 ?d-1 in one millilitre saline, by slowly intraperitoneal injection. In control group, animals received the same dose saline. In sham - operated group, animals were treated in the same manner as previously de-scribed except that coronary ligation was carried out. Fourteen days after surgery, the rats were killed. The hearts were excised and im-mersed into 4% paraformaldehyde in phosphate - buffered saline for more than 48 hours. Subsequently, the whole LV were embedded in paraffin. Transverse serial sections Sjjun thick were cut. HE staining observed the changes of LV structure. MMP - 2 and MMP - 9 were examined with immunohistochemical method. Collagen volume per-centage were examined with special VG staining. All the results were scanned and semi - quantitatively analyzed by computer. SPSS 11.0 software was used to examine all values.Results1. Eighteen of forty - five rats were dead, seven in experimental group, eight in control group and three in sham - operated group, in-cluding early death within 24 hours. Operative mortality of the surgical procedure was 40%.2. Morphometric analysis with HE staining. Myocardial tissue was stained with HE and pathological changes were observed. Forty -five minutes of left coronary artery occlusion followed by reperfusionproduced nontransmural myocardial infarction with sparing of a consid-erable amount of subepicardium as well as a thin rim of endocardium in the infarcted zone. In experimental group and control group, infarc-tion was observed, with myocardial fibre dissolving and broken. More-over, pathological changes were more serious in control group than those in experimental group. Infarct areas of the experimental animals were equal to control animals. However, no infarction was observed in sham - operated group. Compared with the sham ?operated group, the experimental group and control group showed significant increases in LV cavity area, interventricular septum thickness and free wall thickness, and the infracted wall was thinner ( P < 0.05, P<0.01). The changes of diltiazem treated rats were less than those of control group.3. Morphometric analysis with VG stain. Collagen proliferation obviously decreased much more in experimental group than that in control group ( P < 0. 001) , but both increased much more than that in sham - operated rats ( P <0.001). In sham - operated group, little collagen component was observed.4. Staining of MMP -2 and MMP -9 in myocardium with immu-nohistochemical method. The expression of MMP - 2 and MMP - 9 in-creased both in experimental and control group. In control group, the expression of...
Keywords/Search Tags:Ventricular remodeling, Myocardial infarction, Matrix metalloproteinases, Calcium channel antagonists
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