Protective Effects Of Oxymatrine On Injury Induced By Focal Cerebral Ischemia In Rats

Oxymatrine(OMT) is an alkaloid involved in inhibition of sodium currentand the effect of anti-inflammation. Sodium channel blocking drug have knownto protect brain from injury induced by cerebral ischemia. But the effects ofOMT on the focal cerebral ischemia have not been reported yet at present.Therefore, we studied a potential neuroprotective effect and mechanism ofOMT after focal cerebral ischemia in the rats.Ⅰ . Effects of oxymatrine on neurological score and infarct volume ratio infocal cerebral ischemia rats Cerebral ischemia model was produced by occlusion of right middlecerebral artery in rats. Functional neurological score were performed to confirmsuccessful unilateral ischemia in focal cerebral ischemia rats in the study. Extentof ischemic infarction was revealed by reaction with a solution of 2, 3,5-triphenyltetrazolium chloride (TTC) for 20 to 30 minutes. Results showedthat OMT 35, 70, 105mg·kg-1 decrease neurological score and infarct volumeratio in dose dependent manner (p<0.05). Rats treated with OMT administeredafter cerebral ischemia showed significantly smaller infarcted areas than those ofadministration of OMT in advance. The results suggested that OMT have aprotective effect on focal cerebral ischemia rats.II. Effects of OMT on morphology in focal cerebral ischemia ratsHistological analyses using H&E of brains revealed that OMT 35, 70,105mg·kg-1 can lighten the extent of cellular swelling and interstitial edema inbrain in dose dependent manner (p<0.05). It was showed that OMT can protectthe brain from injury after cerebral ischemia.III. The effect of OMT on NO content in serum in focal cerebral ischemia ratsNO content in serum was determined by chromatometry in focalcerebral ischemia rats. NO content in serum of rats treated by OMT35,70,105mg·kg-1 were 5.06±1.17 μmol/l , 4.30±0.35μmmol/l and3.93±0.60μmmol/l,respectively. The results suggested that OMT reducedsignificantly NO content in serum (P<0.05, p<0.01). OMT can against injuryinduced by NO in focal cerebral ischemia rats.IV. The effect of OMT on the activities of MPO in brain in focal cerebralischemia ratsThe activities of MPO were determined by chromatometry in brain offocal cerebral ischemia rats. OMT reduced significantly the activities of MPOin dose dependent manner (p<0.05, P<0.01). It was showed that OMT candecrease infiltration of neutrophil and inhibit inflammatory reaction in focalcerebral ischemia rats.V. The effect of OMT on COX-2 expression in brain of focal cerebral ischemia ratsCOX-2 expression was determined by immunohistochemistry in brain offocal cerebral ischemia rats. COX-2 was expressed in cell of cerebral cortex,gyrus hippocampi beyond the ischemia region in brain of rats and theischemia region in brain of rats of control group. But COX-2 expression wasseldom observed in cell of OMT 105mg·kg-1 group. The cell numberexpressed by COX-2 of OMT105mg·kg-1group was 28.1±3.2 Number/mm2,and that of control was 48.5±4.6 Number/mm2. OMT 105mg·kg-1 decreasedsignificantly the cell expressed by COX-2 compared with the control group(P<0.05) by cell counting. The results suggested that OMT reliefinflammation reaction in focal cerebral ischemia rats.VI. The effect of OMT on GFAP expression in brain of focal cerebral ischemia ratsGFAP expression was determined by immunohistochemistry in brainof focal cerebral ischemia rats. GFAP was expressed greatly in cerebral cortexin rats of control group. OMT 105mg·kg-1 displayed weakly positive in GFAPexpression and decreased the number of cell expressed by GFAP (P<0.05) byusing Excell software. The result implied that OMT decrease the number ofglial cell and protect neuron from injury induced by ischemia.VII. The effect of OMT on ultrastructure in brain of focal cerebral ischemic ratsThe effect of OMT on ultrastructure was observed by electronmicroscopein brain of cerebral ischemia. OMT can lighten the alteration in swollen celland neuropil cavitation and oedema markedly. The results suggested thatOMT can protect the ultrastructure in brain of focal cerebral ischemic rats.In summary, we found that OMT decrease neurological score, infarctvolume ratio and the NO and MPO, COX-2 ,GFAP expression in brain of focalcerebral ischemic rats in the present study. These results showed that OMT havea neuroprotection against cerebral ischemia and anti-inflammatory effect is oneof the mechanism.