| Background and ObjectivesAcute myocardial infarction (AMI) is one of server disease and the incidence is increased year by year. In recent year, many organs and tissues can be reperfused after ischemia for the applying of some afvanced technology. However, it is proved that the function of these organs and tissues becomes deteriorated but not recovered. This pathophysiological process is called ischemia/reperfusion injury. Ischemia/reperfusion injury has become a hotspot in the cardiovascul field since the technology of vascular reconstruction was applied. Myocardial cell apoptosis is one kind of formations during acute myocardial infarction (AMI).Cardiotrophin-1(CT-1) is a cytokine cloned in embryonic stem cell in rats recently,which is expressed in cardiocyte and cardiac myofibroblast and classified to IL-6 family.It regulates the normal physiological process in heart including facilitating normal development of heart and cell survival. As a member of IL-6 family, it has IL-6 -like function and synthesize acute reponse protein to show myocardial preservation. It is proved that more CT-1 can be seen in ischemic myocardium after acute myocardial infarction. It can reduce death of myocyte cells and help those residual cells survive. Besides it help other fibroblast move to make the infarction area recover and protect cardiac function. It is found that CT-1 can help myocardial cell survive in serum-free medium in vitro. CT-1 can cause heat shock protein hsp70, hsp90 to overexpress, which has protective funtion in cultivating neonatal myocyte cells. All above illustrates that CT-1 has a close relationship with myocardial injury and cardiac function.Recent evidence suggests that statins improve the status of patients with coronary artery disease not only by reducing cholesterol level, but also by acting on the level of the endothelium-smooth muscle unit. It is established that statins can increase the level of NO in serum, restrain the overloading of Ca2+, counteract aggregating of platelets, abate the inflammatoty reaction and lower the level of inflammatory factor, which broadens the applying of statins in Atherosclerosis, Myocardial infaraxtion, Acute coronary syndrome and apoplexy of clinical medicine, but which has attracted the attention of scholars the applying of statins in myocardial ischemia/reperfusion injury.In this study, to explore atorvastatin's protection to myocardial cells and possible mechanism of action during ischemia/reperfusion and supply the theoretical evidences to clinical treatment, the effect of atorvastatin on myocardial cell apoptosis induced by ischemia/reperfusion in rats is observed by detecting the expression of CT-1 and TNF-αgenes during ischemia/reperfusion.MethodsNinty-five male SD rats, weiging 220±50g, were used. After raised one week, they were randomly assigned into three groups: sham-operated (C1,C3,C7,C14,C21 )group, I/R(I1,I3,I7,I14,I 21) groups, and atorvastatin (V1,V3,V7,V14,V21) groups. All the rats were fed ordinary food during the whole experiment. At the same time, two groups of rats (group sham, N=30 and group I/R, N=30)were given additional 10ml normal saline(NS) 8:30-9:30 AM daily for 15 days; another groups of rats (groups V, N=30) were fed additional atorvastatin 20㎎·kg-1·d-1 8:30-9:30 AM daily for 15 days too. Fifteen days late, the rats models of myocardial ischemia/reperfussion began to be established. During the experiment, left anterior descending arteries in rats of group I/R and group were obstructed for 30min, group sham were not. Left anterior descending arteries were untied 30 min later and reperfused. After-operation which were collected blood and heart preparation in the first, the third, the seventh, the fourteenth, the twenty-first days.Another blank control group(N=5) of rats were direct collected blood and heart preparation. The level of CT-1 were evaluated by ELISA in serum of rats. The immunohisto -chemistry method was used to detect the expression of the TNF-αin the infarction myocardium. Triphenyl tetrazolium chloride (TTC) method was used to study the percentage of the infarction area. Result1. Morphological changes under light microscopeMorphological chang of myocardial tissues was observed by using of microscope after being stained by HE. Morphological character is almost normal in group sham. Ischemia-reperfusion myocardial cell nuclear enrichment microscope, nuclear shrinking, a large number of myocardial degeneration, myocardial tissue edema, focal necrosis can be seen, a large number of inflammatory cells infiltration, local muscle fibers have eosinophilic change significantly enlarged myocardial fiber, with disorders, a wide range of characteristics such as fibrous tissue hyperplasia, the normal myocardial cell survival than atorvastatin group less. Atorvastatin group microscope myocardial cell nuclear enrichment, nuclear become smaller, less degeneration of myocardial cells, myocardial tissue edema, we can see a small number of necrotic foci, a small amount of infiltration of inflammatory cells, fibrous tissue hyperplasia than to reduce ischemia- reperfusion groups, a large number of normal myocardium. Surviving cells, thickening of myocardial fibers, myocardial fibers with a relatively neat, lesions less than ischemia- reperfusion groups.2. The concentration of CT-1 in the serum.Atorvastatin groups: The concentration of CT-1 in all group was higher there was significant differences than ischemia- reperfusion groups (p<0.05).The concentration of CT-1 was in order decreased in the first day afteroperation ,there was obvious increased and significant differences than ischemia- reperfusion groups all groups(p<0.05) ; and it was highest in fourteenth day, to achieve 1690.69±230.35pg/ml, which was not significant difference with I14 groups (p>0.05). Then the concentration of CT-1 were fall-off.3. The expression of TNF-αin infarction tissueControl group: there was little expression of TNF-αin tissue. Ischemia- reperfusion groups: The expression of TNF-αin I1 group was increased, and was significance difference with the control group (p<0.05). And the expression of TNF-αin I3 group was also increased. And the expression of TNF-αin I7 group was highest, and was significant difference with control group (p<0.01). The expression of TNF-αin I14 and I21 group were lower than I7 group, but its level was still higher than the control group (p<0.05). Atorvastatin groups: The expression of TNF-αin V3 group was lower than that in I3 group, and had significant differences (p<0.05). V10 and V14 groups are the same.4. Determination of myocardial infarct sizeIschemia-reperfusion groups and atorvastatin groups intervention both in myocardial infarction after surgery, while the sham-operated groups after myocardial infarction does not appear, there is no control groups myocardial infarction; ischemia-reperfusion myocardial infarction in each group area were larger, the average reached 26.81%, atorvastatin intervention group were significantly reduced myocardial infarction size, with an average of 22.98 percent, compared to the two groups were statistically significant differences (p<0.01).Conclusion:1. The expression of CT-1 in rats of Atorvastatin drug intervention groups was significantly higher than myocardial ischemia-reperfusion groups, and the area of myocardial infarction was decreased than ischemia-reperfusion groups. CT-1 as an endogenious protective substrate against ischemia-reperfusion injury, on myocardial ischemia-reperfusion injury has a protective effect.2. After ischemia-reperfusion in rat myocardial TNF-αprotein expression was significantly increased, atorvastatin drug intervention to reduce TNF-α, and the area of myocardial infarction than myocardial ischemia-reperfusion groups decreased. TNF-αmay be missing reperfusion myocardial injury in blood plays an important role.3. Atorvastatin drug interventions can reduce ischemia-reperfusion myocardial infarction area, the promotion of CT-1 expression and release, inhibition of TNF-αexpression and release may be the protection of atorvastatin myocardial reperfusion injury defect mechanism one. |
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