Protective Effects And Mechanisms Of Levocarnitine On Focal Cerebral Ischemia Reperfusion Induced Injury Rats

Objective:To investigate the potential protective effects of Levocarnitine on cerebral ischemia-reperfusion (I/R) injury in rats and analyze the possible mechanism of action of Levocarnitine in preventing and treating ischemic cerebrovascular disease.Methods:fifty-two healthy male Wistar male rats were randomly divided into four groups: group A was the sham operation group, group B was the physiological saline-controled group and received only normal saline intraperitoneally injection, group C was the 100mg/kg Levocarnit-ine group and received 100 mg/kg Levocarnitine intraperitoneally injection, the fourth group D was the 200mg/kg Levocarnitine group and received 200 mg/kg Levocarnitine intraperitoneally injection, each group of thirteen rats. The models of the focal cerebral I/R rats were made by the middle cerebral artery occlusion (MCAO) except sham-operation group. After ischemia for 2h and reperfusion for 24h, neurological function deficit was scored by using the Longa scoring system at 24h after operation. Then the rats were sacrificed by head cutting and the brain was taking out. succinic dehydrogenase (SDH) activity were measured in the cerebral mitochondria and ATPase,malondialdehyde(MDA) levels and superoxide dismutase (SOD) activity were measured in the cerebral tissues by spectrophotometry. The pathological feature of cerebral tissue was detected by HE staining and Caspase3 expression in cerebral tissue around infarct area were detected by immunohistochemistry. SPSS 13.0 version was used for statistical analysis and P<0.05 was regared as statistical significance.Result:1,Levocarnitine treated groups (100mg/kg,200mg/kg) significantly enhanced the activity of SDH, improved the activity of ATPase,suppressed MDA content, prevented reduction of SOD activity in comparison with the saline-controled group.2,Levocarnitine treated groups (100mg/kg,200mg/kg) changes of cerebral ischemic impairment were lighter than that in saline-controled group, and in Levocarnitine 200mg/kg treated group the changes were lighter than that in Levocarnitine 100mg/kg treated group.3,Compared with sham operation group, in saline-controled group expressions of caspase-3 elevated at reperfusion in ischemic region (P<0.01). Compared with saline-controled group, in Levocarnitine treated groups (100mg/kg,200mg/kg) significantly reduced to the expression of caspase-3 (P＜0.01). Conclusion:Levocarnitinehas a potent neuroprotective effect against cerebral ischemia-reperfusion induced injury. The protective neural function mechanisms may be derived from:1,improving the energy metabolism,enhancing the activity of ATPase and maintaining the stability of sodium pumps and calcium pumps.2,enhancing the activity of SDH and protecting the function of mitochondrion and improving the energy metabolism in the cerebral mitochondria.3,enhancing the activity of the antioxidant system, improving clearance of free radical and decreasing the incidence of free radical-induced lipid peroxidation.4,reducing the expression of caspase-3 protein and inhibiting cell apoptosis in rat brain.