| Objective: To explore the changes of cardiac microcirculation after heart failure after myocardial infarction.To detect the effect of improve the cardiac microcirculation on heart failure and its possible mechanism.To investigate the effect of applying drugs in rabbits with heart failure on the improvement of microcirculation.Methods:1.According to the random number table,40 New Zealand rabbits were randomly divided into heart failure group,sham group,nicorandil group and YQFM group.2.The model of heart failure after myocardial infarction was made by ligation of the left anterior descending coronary artery.The cardiac function of rabbits was examined by cardiac ultrasound 2 weeks after operation.Rabbits with left ventricular ejection fraction(LVEF)<50% indicated that the heart failure model was successful.The rabbits in the sham group were only subjected to thoracotomy without ligation of the coronary artery.After the model was constructed,the nicorandil group was given nicorandil 75mg/mL in saline at 2mL/(kg·d)for 4 weeks by intraperitoneal injection.The YQFM group was given YQFM 75mg/mL in saline at 2mL/(kg·d)for 4 weeks by intraperitoneal injection.In the sham group and heart failure group,an equal dose of 0.9% saline 2mL/(kg·d)was given for 4 weeks.Rabbits were sacrificed at 6 weeks after surgery.3.Cardiac ultrasound was measured at preoperative,2 weeks of operation and 6 weeks of operation by the same ultrasound specialist.LVEF and the left ventricular end diastolic diameter(LVEDD)was measured.The measured values are averaged 3 times.4.Arterial blood was collected before operation,2 weeks after operation operation and 6 weeks after operation.The level of BNP in serum was measured by ELISA.5.The mRNA expression of eNOS,ICAM-1,VEGF in myocardial infarction tissues was detected by Real-Time PCR at 6 weeks after operation.6.The protein expression of p-Akt,eNOS,ICAM-1,VEGF in myocardial infarction tissues was detected by Western-Blot at 6 weeks after operation.7.The pathological changes of myocardium were observed by HE staining.The expression of CD31 was detected by immunohistochemistry,and the capillary density was calculated.8.The microcirculation and ultrastructure of myocardial tissue were observed by transmission electron microscopy(TEM).Results:1.In addition to the sham group,the LVEF <50% at 2 weeks after operation in the other three group.Compared with the sham group,the LVEF decreased significantly(P<0.05)at 6 weeks after operation in the heart failure group,and the LVEDD increased significantly(P<0.05).Compared with heart failure group,the LVEF increased significantly(P<0.05)and the LVEDD decreased significantly(P<0.05)in nicorandil group and the YQFM group at 6 weeks after the operation.2.Compared with the sham group,the concentration of BNP in the serum was significantly increased in heart failure group at 6 weeks after the operation(P<0.05).Compared with the heart failure group,the BNP concentration in nicorandil group was decreased,but there was no significant difference(P>0.05)and the BNP concentration in YQFM group was decreased significantly(P<0.05).3.At 6 weeks after operation,compared with heart failure group,the expression of eNOS mRNA in nicorandil group was significantly increased(P<0.05),the expression of ICAM-1 mRNA in nicorandil group and YQFM group was significantly decreased(P<0.05),and the expression of VEGF mRNA in nicorandil group and YQFM group was significantly increased(P<0.05).4.At 6 weeks after operation,compared with heart failure group,the expression of p-Akt and VEGF protein in nicorandil group and YQFM group was significantly increased(P<0.05),the expression of ICAM-1 protein in nicorandil group and YQFM group was significantly decreased(P<0.05),the expression of eNOS protein in nicorandil group was significantly increased(P<0.05).5.HE staining results: myocardial cell necrosis and myocardial fiber disorder were found in heart failure group.Myocardial cells edema and irregular myocardial fiber arrangement in the myocardial tissue was found in nicorandil group and YQFM group.6.Immunohistochemistry results: The capillary density in nicorandil group and YQFM group was significantly higher than that in heart failure group.7.Transmission electron microscopy(TEM)results: microvascular basal membrane rupture and vascular endothelial cell structure failure was found in heart failure group.The injury in nicorandil group and YQFM group was lighter than that in heart failure group.Conclusion:1.The study confirmed the occurrence of microvascular structure obstruction and dysfunction in rabbits with heart failure after myocardial infarction.2.Vascular endothelial cells was involved in the process of heart injury in rabbits with heart failure after myocardial infarction,which promoted the occurrence of heart failure.3.Drugs can reduce microcirculation damage by improve endothelial function in rabbits and play a role in improving heart failure. |
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