| Myocardial ischemia is the reduction of hemoperfusion and the myocardial energy metabolism is not normal, which can not support the heart to work.Several pathogenic mechanisms have been proposed to explain the myocardial damage that occurs during myocardial ischemia injury. The oxidative stress has been shown to play a crucial role in the pathogenesis of ischemia injury. Apoptosis is the cellular basis in oxidative stress induced by ischemia injury. It has been demonstrated that scavenging the free radical could protect the myocardium against myocardial ischemia injury ,ameliorate myocardial function .As an important chemical mediator and celluar signal molecular , nitric oxide has been attracting the attention of every researcher in medical domain. Many studies have examined the role of nitric oxide in physiological and pathophysiological process. Endogenous NO is mainly producted from L-Arginine by nitric oxide synthase (NOS) .It has been shown that NO plays an important physiological role in dilating vascularity, regulating blood pressure, inhibiting vascular remodeling, inhibiting platelet aggregation and protecting the myocardium. It has also been found that NO plays a very important role in myocardial ischemia-reperfusion and has a protective effect.However, the role of NO in myocardial ischemia requires a great deal of further study .We therefore investigate the change of NO in a rat model of myocardial ischemia in vivo and observe the effects of aminoguanidine on acute myocardial ischemia in rats.Part 1 Change of endogenous nitric oxide/nitric oxide synthase system in acute myocardial ischemia ratsObjective: To observe the changes of NO/NOS system in acute myocardial ischemia at different ischemia time in rats.Methods: Eighty male rats were randomly divided into ten groups.①sham 1h group;②sham 3h group;③sham 6h group;④sham 9h group;⑤sham 12h group;⑥ischemia 1h group;⑦ischemia 3h group;⑧ischemia 6h group;⑨ischemia 9h group;⑩ischemia 12h group(n=8). After being anesthetized by 10% chloral hydrate (300mg/kg), All rats were subjected to openning chest then the left anterior desending coronaries(LADC) were ligated, while the LADC was not ligated in sham group rats. The electrocardiogram(ECG) was recorded under anesthetized condition. The ST-segment in ECG was elevated more than 0.15mv, which was regared as successful model .The cardiac function indexes such as the left ventricular systolic pressure(LVSP), the left ventricular developed pressure (LVDP), the left ventricular end diastolic pressure (LVEDP) and±dp/dtmax were respectively recorded at 1,3,6,9 or 12 hour after ligation.The content of NO in serum and the activities of iNOS and cNOS in myocardium were respectively detected.Results:1. In sham group,the LVEDP,LVDP and±dp/dtmax were not altered from 1 hour to 12 hour after ligating LADC. Compared with those of the sham group,the LVEDP, LVDP and±dp/dtmax were not altered at 1 hour (P > 0.05);The LVDP and±dp/dtmax were significantly decreased and the LVEDP was markedly increased at 3 hour after ischemia (P﹤0.05, P﹤0.01), during 6 hour to 12 hour after ligating LADC the cardiac function parameters were significantly decreased compared with those of sham group (P < 0.05, P < 0.01)2. In sham group, the content of NO in serum and the activities of iNOS and cNOS in myocardium were not altered from 1 hour to 12 hour. Compared with those of the sham group, the content of NO in serum was increased at 3 hour after ischemia and was peaked at 9 hour in rats (P <0.05). At 3 hour after ischemia, the activity of iNOS in myocardium tissue was increased, while the activity of cNOS in myocardium was decreased compared with that of the sham group(P<0.05).The iNOS activity was peaked at 6 hour (P<0.05), while cNOS activity was unceasingly decreased to reach the trough at 9 hour afer ischemia in rats(P<0.05).Summary:The content of NO in serum and the activities of iNOS and cNOS in myocardium were not altered at 1 hour after ischemia in rats. During 3 hour to 12 hour after myocardial ischemia the content of NO in serum and the activity of iNOS in myocardium were markedly incerased.It could be concluded that NO/NOS system may be play a important role in the physiopathologic process of acute myocardial ischemia in rats.Part 2 Effects of Aminoguanidine on the reaction of oxidative stress in acute myocardial ischemia ratsObjective: To study the effect of aminoguanidine on acute myocardial ischemia and explore its possible molecular mechanisms from the reaction of oxidative stress in rats.Methods: Twenty-four male rats were randomly divided into three groups(n=8)①shamgroup;②ischemiagroup;③ischemia+ aminoguanidine(AG) group(100mg/kg) .The left anterior descending coronary (LADC) was ligatded, while it was not ligated in sham group rats.AG(100mg/kg) was administrated at 6 hour after ischemia in ischemia+AG group rats. The rats were killed at 9 hour after ischemia. The content of NO and the activity of LDH in serum, the activities of iNOS and cNOS in myocardium were respectively detected. The activities of SOD, GSH-PX and the content of malondialdehyde (MDA) in myocardial tissue were measured in rats.Results:1. The content of NO in serum was increased after ischemia,iNOS activity in myocardial tissue was significantly increased(P<0.01), while cNOS activity was decreased in ischemia group compared with that of the sham group in rats(P<0.05). Compared with those of ischemia group, the content of NO in serum and the activity of iNOS were decreased in ischemia+AG group,but the activity of cNOS was not significantly altered in rats.2. In ischemia group,the activities of SOD and GSH-PX were signify- cantly decreased, the content of malondialdehyde (MDA) in myocardial tissue and the activity of LDH in serum were significantly increased(P﹤0.01) compared with those of sham group. Compared with those of ischemia group, the activities of SOD and GSH-Px were significantly increased , the content of MDA in myocardial tissue and the activity of LDH in serum were significantly decreased in ischemia+AG group. (P < 0.05 or P < 0.01).Summary:It could be concluded that aminoguanidine has a beneficial myocardial protection against the ischemia injury in rats by ameliorating the function of myocardium tissue,upregulating the activities of SOD and GSH-PX and downregulating the content of MDA and the activity of LDH.Part 3 Effects of Aminoguanidine on the reaction of apoptosis in acute myocardial ischemia ratsObjective: To study the effect of aminoguanidine on acute myocardial ischemia and explore its possible molecular mechanisms from the reaction of apoptosis in rats.Methods: Twenty-four male rats were randomly divided into three groups(n=8)①s hamgroup;②ischemiagroup;③ischemia+aminoguanidine(AG)group(100mg/kg).The left anterior descending coronary (LADC) was ligated in ischemia group rats while it was not ligated in sham group rats. AG (100mg/kg) was administrated at 6 hour after ischemia in ischemia+ AG group. The rats were respectively killed at 9 hour after ischemia. The apoptotic rate of cardiomyocytes was evaluated by TUNEL. The expressions of Bcl-2 and Bax in cardiomyocytes were respectively detected by immunohistochemistry. The histomorphology changes of myocardium were obersved by light microscope.Results:1. The apoptotic rate of cardiomyocytes and the expression of Bax in ischemia group were significantly increased compared with those of sham group (P<0.01). Compared with those of ischemia group, the apoptotic rates of cardiomyocytes and the expression of Bax were markedly decreased and the expression of Bcl-2 was markedly increased in ischemia+AG group in rats (P < 0.01).2. In sham group , myocardial cells arranged in neat rows and colored evenly. Myocardial fiber striped or disappeared, the nuclear migrated and even cracking disappeared and inflammatory cells infiltrate in ischemia group compared with those of sham group. The injury of the myocardium was decreased in ischemia+AG group compared with those of ischemia group .Summary:It could be concluded that amionguanidine has a beneficial myocardial protection against the ischemia injury in rats by ameliorating the function of myocardium tissue, upregulating the expression of Bcl-2,downreg- ulating the expression of Bax.Conclusions:1 The content of NO in serum and the activities of iNOS and cNOS in myocardium were not altered at 1 hour after ischemia in rats. During 3 hour to 12 hour after myocardial ischemia the content of NO in serum and the activity of iNOS in myocardium were markedly incerased.It could be concluded that NO/NOS system may be play a important role in the physiopathologic process of acute myocardial ischemia in rats.2 It could be concluded that aminoguanidine has a beneficial myocardial protection against the ischemia injury in rats by ameliorating the function of myocardium tissue,upregulating the activities of SOD and GSH-PX and downregulating the content of MDA and the activity of LDH.3 It could be concluded that amionguanidine has a beneficial myocardial protection against the ischemia injury in rats by ameliorating the function of myocardium tissue, upregulating the expression of Bcl-2,downreg- ulating the expression of Bax.
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