| Acute myocardial infarction (AMI) is the disease which severely menaces people's health. Thrombolytic therapy and percutaneous transluminal coronary angioplasty (PTCA) can save a large number of myocardium which is dangerous to death , but they also cause a serious problem of myocardial ischemia-reperfusion injury. It has been found that inducible heme oxygenase was involved in many oxidative stress process in vivo and showed protective effect on ischemia-reperfusion injury.Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). In mammals, biliverdin is rapidly converted by the enzyme biliverdin reductase. There are three isoforms of HO: HO-1, HO-2 and HO-3. HO-lis highly inducible, a variety of factors have been shown to induce HO-1 expression in tissue and increase its activity. Recent studies demonstrated that high expression of HO-1 could relieve the tissue injury of ischemia-reperfusion and has protective effects, but the mechanism of protection of HO-1 is yet not clear, especially whether the HO-1 and its products of bilirubin, CO are involved in the myocardial ischemia-reperfusion in vivo is not reported. In this experiment, the rat myocardial ischemia-reperfusion models were established by ligating the left anterior descending artery, the expression of HO-1 was induced by hemin and inhibited with zinc protoporphyrin IX (ZnPP). The aims are to observe the protective effect of HO-1 on myocardial ischemia-reperfusion and to explore the mechanism by measuring the concentration of bilirubin in serum, thecontents of CO in blood plasma, the activities of superoxide dismutase (SOD) and the contents of molondialdehyde(MDA) in myocardium.Method88 health male Sprague-Dawley rats, weighing from 250 to 300 grams, were randomly divided into four groups: I group, II group, III group and IV group. The rat models of myocardial ischemia-reperfusion were established by coronary ligation. The animals were handled as follows: (1) HI group: intraperitoneal injection of hemin(30mg-kg-1) was performed for two consecutive days prior to the operation; (2) IV group: the administration of hemin was same as that of III group, and ZnPP(20mg-kg-1) was administered intraperitoneally 24 hours prior to the operation. (3) I group and II group was administered the same dosage of physiological saline intraperitoneally. All animals were anesthetized by intraperitoneal administration of 3% sodium pentobarbital (45mg-kg-1). A thread was placed under the left anterior descending artery, but not ligated in I group. Blood was sampled from heart after 30 minutes ischemia followed by 60 minutes reperfusion to detect the activity of creatine kinase and the concentration of bilirubin in serum, the content of CO in blood plasma respectively. The hearts were fetched out and cleaned with cold saline, the left ventricles were isolated and homogenated to determine the activities of superoxide dismutase(SOD) and the contents of MDA. Heart slices stained by 2,3,5-triphenylterazolium chloride(TTC) sodium were used to determine the size of infarction. Immunohistochemical staining of myocardium was performed and the expression of HO-1 was analyzed with computer image analysis system. The myocardial sections stained with hemotoxylineosin(HE) were used to examine the pathological changes under light microscope. The data were processed with SPSS 10.0Results1. The expression of HO-1 in ffl group and IV group were significantly stronger than that in II group(P<0.01), and in III group, it was significantly stronger than that in IV group(P<0.01). There was no significant difference between II group and I group (P>0.05).2. The activities of creatine kinase in II group, III group and IV group were significantly higher than that in I group (P<0.01), however, it was significantly lower in III group than that in II group(P<0.01). While there was no significant difference between IV group and II group (P>0.05).3. The size of myocar...
|
PDF Full Text Request