Background:Coronary microthromboembolism is a very common phenomenon during the attack of acute coronary syndrome and the procedure of PCI, but the existing animal model can not analogue the pathophysiology of coronary microthromboembolism exactly. The cardiac myocytes necrosis following ischemia occurs after microthromboembolism, but the myocardial remodeling and degression of cardiac function can not be explained by cardiomyocytes necrosis only, so more and more research come to focus on cardiomyocytes apoptosis.The research targets on establish a new type of coronary microthromboembolism model. Using the new rat model, we observe the effects on cardiomyocytes apoptosis and cardiac function after coronory microthromboembolism. Furthermore the contribution of telmisartan, a type of ARB, on the microthrombogenesis and cardiac myocytes apoptosis has been investigated. Methods:Acute experiment: All of the SD rats were divided into three groups randomly: Rats of microthrombus group was injected 400 ug sodium laurate into the coronary arteries;Rats of telmisartan group was administered with telmisartan (10mg/kg/d) by drinking water, after 7 days, 400 ug sodium laurate was injected into the coronary arteries;The control group had all the same steps with microthrombus group except normal saline instead of sodium laurate. 24 hour after injection, the blood samples of all the rats was collected to detect cTnI;After paraffin imbedding rats heart, the microthrombus are detected by HE staining and cardiomyocytes apoptosis is detected byTUNEL staining.Chronic experiment: The surviving rats which were injected sodium laurate were randomized into two groups: microthrombus group and telmisartan group. The rats of telmisartan group were administered telmisartan lOmg/kg/d by drinking. The control group injects normal saline instead of sodium laurate. UCG was applied to evaluate cardiac function before and 28 days after injection. Apoptosis myocardial cells were detected by TUNEL staining 28 days after injection. Results:1. Acute experiment: 24 hour after injection, microscopic examination of HE stained sections revealed that microthrombus formed in the coronary microcirculation in microthrombus group and telmisartan group, both the microthrombus ratio of the above two groups were significantly higher than control group (p<0.001), but there was no difference between microthrombus group and telmisartan group (p=0.319). cTnl concentration of microthrombus and telmisartan group was significantly higher than control group (PO.001), but the difference between microthrombus group and telmisartan group was not significant (p-428). Compare with control group, apoptosis index of cardiac myocytes detected by TUNEL staining in microthrombus group (p<0.001) and telmisartan group (p=0.001) was higher. There was also not difference between microthrombus group and telmisartan group.2. Chronic experiment: 28 days after injection, compare with control group, the LVEDD of microthrombus group is increasing (p=0.004), and the LVEF is decreasing (pO.OOl). As to the telmisartan group, the LVEDD is smaller than microthrombus group (p=0.035) as well as LVEF is higher than microthrombus group(p=0.003). Besides, Apoptosis index of cardiomyocytes in microthrombus group is still increased significantly contrasting with control group (p=0.001).Apoptosis index of myocardial cells of telmisartan group is lower than microthrombusgroup (p=0.024).Conclusion:1. By injecting sodium laurate into the coronary arteries, a new model of microthrombosis in rats is successfully developed;2. Advance administration of telmisartan cannot degrade the rate of thrombogenesis;Coronary microthrombus may up-regulate the apoptosis of cardiomyocytes which may be one of the reason that cause cardiac function degression;3. Telmisartan can suppress ventricle remoldling, improve cardiac function efficiently, and inhibit the apoptosis of cardiaomyocytes after microthrombogenesis in coronary artery. |