| Imipramine(Imi) is one kind of antidepressants. It is mainly used to cure all kinds of depressions.Good effects will be got in the treatmeant of depression after focal cerebral ischemia.In the studies of our department, Imipramine selectively inhibited the basilar artery ring of rabbits. In recent studies, the protective effects of Imi on ischemia injury in cultured rat cerebral neurons were observed. It maybe attribute its mechanism to antioxidation and calcium antagonism. It is not reported that the protective effects of Imi on cerebral ischemia-reperfusion injury. The rat model of focal cerebral ischemia-reperfusion was established with the middle cerebral artery occlusion (MCAO) by reversible inserting a nylon thread method. In this study, the purpose of this study is to investigate the protective effects of Imi on cerebral ischemia-reperfusion injury. MethodsThe rat model of focal cerebral ischemia-reperfusion was established with the middle cerebral artery occlusion(MCAO) by reversible inserting a nylon thread method. In this study ,216 healthy Wistar rats(280-320g) were randomly divided into six groups. Namely, sham operation group,cerebral ischemia-reperfusion (I/R) group,Nimodipine (Nim)2mg/kg group,three dose groups Imi(20,10,5mg/kg respectively). The drugs were administed by intraperitoneally(ip) before established MCAO sixty minutes. Rats were killed after ischemia 1 houre and reperfusion 2 hours. Brain were fetched out and measured the contents of [Ca2+]i ,H2O,NO,MDA and the activites of SOD and NOS .The sections were stained with hemotoxylin-eosin(HE), histological changes of brains were also observed in other six rats.Results:1 The effects of Imi on Ca2+ contents in the brain.1.1 Compared with sham operation group, Ca2+ content was higher remarkably in cerebral ischemia-reperfusion groups(P<0.01).1.2. Compared with I/R group, Ca2+ content was lower remarkably in Imi 20,10,5mg/kg and Nim 2mg/kg groups(P<0.01).2 The effects of Imi on H2O contents in the brain.2.1 Compared with sham operation group, H2O contents was higher remarkably in cerebral ischemia-reperfusion groups(.P<0.05).2.2. Compared with I/R group, H2O contents was lower remarkably in Imi 20,10,5mg/kg and Nim 2mg/kg groups(P<0.05).3 The effects of Imi on activities of SOD and MDA contents in the brain.3.1 Compared with sham operation group, the activities of SOD was significally lower,but MDA contents was higher remarkably in cerebral ischemia-reperfusion groups(P<0.05).3.2 Compared with I/R group,the activity of SOD was significally increased, but MDA contents was decreased remarkably in Imi 20,10mg/kg and Nim 2mg/kg groups(P<0.05).4 The effects of Imi on activities of NOS and NO contents in the brain.4.1 Compared with sham operation group, the activity of NOS and NO content were significally increased in cerebral ischemia-reperfusion groups(P<0.05).4.2 Compared with I/R group,the activities of NOS and NO contents was significally decreased in Imi 20,10mg/kg and Nim 2mg/kg groups(.P<0.05).5 The effects of Imi on the numbers of positive expression of apoptotic neurons in the brain.5.1 Compared with Sham operation group, the numbers of positive expression of apoptotic neurons was significally increased in cerebral ischemia-reperfusion groups(P<0.01).5.2 Compared with I/R group, the numbers of positive expressionof apoptotic neurons was significally decreased in Imi 20mg/kg group (P<0.01).6 The effects of Imi on the pathological change in the brain.The cerebral ischemia-reperfusion group injury was heaviest, there were cerebral edema widely,neuronal cells necrosis and partial formation malactic focal. In the Imi 20,10mg/kg and Nim 2mg/kg groups showed that brain edema and neuronal cells necrosis were relieved, and the formation malactic focal was decreased. Conclusions:1. This study demonstrates that Imi has protective effects on cerebral ischemia-reperfusion lesion.2. The possible protective mechanism of Imi might be associated with decreasing of [Ca2+]i...
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