ABSTRACT
OBJECTIVE： To observe improvement effects of fingolimod on middle cerebral artery occlusion/reperfusion （MCAO/R） injury model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and fingolimod low-dose， medium-dose and high-dose groups （0.5， 1， 2 mg/kg）， with 8 rats in each group. Except for sham operation group， MCAO/R injury model was induced by suture-occluded method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion [1 h after reperfusion （1st day）， 22.5 h after reperfusion （2nd day）， and then every 24 h until 142.5 h of reperfusion （7th day）]. Sham operation group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 7 d. The scores of neurological deficit and balance beam test， the times of memory error [work memory error （WME）， reference memory error （RME） and total error] were recorded in each group. The contents of serum inflammatory cytokines （IL-6， IL-8， IL-10， TNF-α） were determined by ELISA， and triphenyl tetrazolium chloride staining method was used to detect the rate of cerebral infarction. RESULTS： Compared with sham operation group， neurological deficit scores （at different time points of 1st-7th day after administration）， balance beam test scores （2nd， 4th， 7th day after administration）， times of memory error （2nd， 4th， 7th day after administration）， the contents of serum inflammatory cytokines and the rate of cerebral infarction were increased significantly in model group （P＜0.05 or P＜0.01）. Compared with model group， neurological deficit scores （low-dose group at different time points of 3rd-7th day， medium-dose and high-dose groups at different time points of 2nd-7th day after administration）， balance beam test scores （low-dose group at 7th day， medium-dose group at 4th and 7th day， high-dose group at 2nd， 4th， 7th day）， RME times and total error times （low-dose group at 4th and 7th day， medium-dose group and high-dose group at 2nd， 4th， 7th day after administration）， WME times （administrations groups at 7th day after administration）， serum contents of IL-6， IL-8 and IL-10 （administrations groups）， serum contents of TNF-α （medium-dose and high-does groups） and cerebral infarction rate （medium-dose and high-dose groups） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Intragastric administration of fingolimod can significantly reduce neurological deficit score， balance beam test score and the times of memory error in MCAO/R injury model rats， and has a protective effect on cerebral tissue and memory function. These effects may be related to the down-regulation of inflammatory cytokines such as IL-6 and TNF-α by fingolimod.
ABSTRACT
Aim To study the protective effects of allicin on acute cerebral ischemia reperfusion injury. Methods The model of cerebral ishemia-3 h/reperfusion-24 h was induced by middle cerebral artery occlusion(MCAO) in SD rats. Allicin(10,20 mg?kg -1) was administered once daily in rats:at 0 h of reperfusion. After 24 h reperfusion, the content of malondialdehyde(MDA),the activities of superoxide dismutase(SOD),GSH and myeloperoxidase(MPO) in brain tissue,the content of NO in plasma were measured. Results Compared with vehicle group, the activity of SOD was increased from 205.87?16.52 to 259.77?19.65 and 284.54?21.79 by allicin 10,20 mg?kg -1; the MDA content was decreased from 38.69?0.10 to 28.68?1.37 and 20.97?0.44 respectively; the GSH content was increased from 28.31?0.64 to 36.19?1.12 and 47.96?0.44 respectively; the NO content was decreased from 29.7?0.49 to 27.38?1.46 and 23.00?0.71 respectively; the MPO content was decreased from 0.29?3.06?10 -2 to 0.26?2.13?10 -2 and 0.23?7.52?10 -2 respectively. Conclusion The protective effects of allicin on acute cerebral ischemia reperfusion injury may be related to increasing antioxidase activities,decreasing lipid peroxidative damage and inhibiting inflammation reaction.