Protective Effects Of Oxymatrine On Focal Cerebral Ischemia Reperfusion Injury In Rats

Oxymatrine (OMT) is an alkaloid isolated from Sophora flavescans Ait.Oxymatrine is an alkaloid involved in effects of sedative,relieve fever,anti-inflammation,antiarrhythmia. But the effects of OMT on the focal cerebralischemia reperfusion have not been reported yet at present. Therefore, westudied a potential neuroprotective effect and mechanism of OMT after focalcerebral ischemia reperfusion in the rats.I. Effects of OMT on acute cerebral ischemia and anoxia in miceThe experiment of quick decapitation and anoxia under normal pressuremodel in mice was used to observe effects of OMT on acute cerebralischemia and anoxia in mice treated by intraperitoneal injection beforeischemia and anoxia.Results showed that OMT49mg·kg^-1,OMT 98mg·kg^-1,OMT 147mg·kg^-1 can prolong the gasping time of mice after quickdecapitation and the survive time of anoxic mice compared with controlgroup(P<0.05).II. The effect of OMT on the neurological score and the infarctvolume ratio after cerebral ischemia reperfusion in ratsCerebral ischemia reperfusion injury model was produced by 120minocclusion of right middle cerebral artery occlusion and reperfusion wasallowed for 24 hours in rats. The neurological score was performed andthe infarct volume ratio was estimated by 2, 3, 5-triphenyltetrazoliumchloride (TTC) staining. Results showed that OMT35mg·kg^-1,70mg·kg^-1,105mg·kg^-1 can decrease neurological score and infarct volume ratio indose dependent manner after cerebral ischemia reperfusion in rats.III. The effect of OMT on morphology in brain after cerebral ischemiareperfusion in ratsThe pathological alteration was showed in brain stained by H&Eafter focal ischemia reperfusion in rats. OMT 35mg·kg-1, 70 mg·kg-1, 105mg·kg-1can lighten the extent of cellular swelling and interstitial edemain brain. It was showed that OMT could protect the brain from injuryafter cerebral ischemia reperfusion in rats.IV. The effect of OMT on NO content in serum after cerebral ischemiareperfusion in ratsNO content in serum was determined in focal cerebral ischemia reperfusionrats. OMT 35 mg·kg-1, 70mg·kg-1, 105mg·kg-1 reduced significantly NOcontent in serum compared with control group (P<0.05). And OMT canantagonize injury induced by NO.V.The effect of OMT on MPO in brain after cerebral ischemiareperfusion in ratsThe activities of brain MPO were measured by chromatometry inbrain of cerebral ischemia reperfusion rats. OMT reduced significantlythe activities of MPO compared with control group (P<0.01). It showedthat OMT can antagonize injury induced by MPO and its mechanism ispossibly correlated with anti-inflammation.VI. The effect of OMT on COX-2 expression in brain after cerebralischemia reperfusion injury in ratsCOX-2 expression was determined by immunohistochemistry in brainof cerebral ischemia reperfusion rats. COX-2 expression in brain in shamgroup has not been observed. COX-2 expression can be observed in controlgroup,LLT group and OMT 35mg·kg-1, 70mg·kg-1, 105mg·kg-1 group.OMT 105mg·kg-1 reduce significantly (P<0.01).Result showed OMT candecrease expression of COX-2 in brain and its mechanism was involvedin anti-inflammation.VII. The effect of OMT on GFAP expression in brain after cerebralischemia reperfusion in ratsGFAP expression was determined by immunohistochemistry in brainof cerebral ischemia reperfusion rats. OMT35mg·kg-1, 70mg·kg-1, 105mg·kg-1 can reduce GFAP expression in brain. The effect of OMT 105mg·kg-1 was most significantly among groups (P<0.05).VIII. The effect of OMT on ultrastructure in brain after cerebral ischemicreperfusion in ratsThe effect of OMT on ultrastructure was observed by electronmicroscopein brain of cerebral ischemia reperfusion rats. Result showed that OMT35mg·kg-1,70mg·kg-1,105mg·kg-1 had a lighter injury on mitochondrion andmembrane structure than control group. OMT lightened the alteration inultrastructure in brain after ischemia reperfusion in rats and antagonizedinjury induced by cerebral ischemia reperfusion.In conclusion,OMT can prolong the gasping time of mice after quickdecapitation and the survive time of anoxic mice and have a protectiveeffects after cerebral ischemia and anoxia. It can decrease neurologicalscore and the infarct volume ratio;It can reduce significantly NO contentin serum;It reduced significantly the activities of MPO and decreasedexpression of COX-2, GFAP expression in brain. OMT lightened the alterationof ultrastructure in brain. Therefore, OMT can protect the brain from injuryinduced by cerebral ischemia reperfusion in rats. The anti-inflammatoryeffect of OMT is possibly one of the mechanisms.