Protective Effects Of Diallyl Sulfide On Cerebral Ischmia-reperfusion Injury In Rats And Its Mechanism

Diallyl Sulfide (DAS), the main organosulphur component of garlic, has multiple pharmacological actions such as anti-inflammatory, anti-oxidant, anti-platelet aggragation, antimicrobial, anti-cancer activities. DAS can pass through blood–brain barrier and has good lipid solubility, based on which, reseachers have pay more attention to its activity on preventive treatment or protective effects in cerebrovascular disease. In this study, we design to investigate its possible mechanisms and effective doses on focal cerebral ischemia-reperfusion injury in rats.Methods: Animals were randomly divided into five groups: the sham operation group; focal cerebral ischemia reperfusion group; 100mg/kg DAS pretreatment group; 150mg/kg DAS pretreatment group and 200mg/kg DAS pretreatment group. Animals were administered DAS100,150,200mg/kg, ip, qd×7d before transient MCAO. Middle cerebral artery occlusion/reperfusion rat's models were performed by intraluminal middle cerebral artery occlusion(MCAO) for 2h, followed by reperfusion for 24h, DAS neuroprotective effects and possible mechanisms were studied. (1)The neuroscore and the volume of cerebral infarction were measured to investigate its neuroprotective effects and best effective dose on reperfusion 24h. (2)the changes of superoxide dismutase(SOD),malondialdehyde(MDA) were observed in animals with sham operation group, focal cerebral ischemia reperfusion group, 200mg/kg DAS pretreatment group. Moreover, apoptotic cells were counted by TUNEL staining and the expression of Nrf2, NQO1, Bcl-2, caspase3 were detected by Immunofluorescence and Western blot.Results: (1)With the use of 100mg/kg, 150mg/kg and 200mg/kg of DAS, neurological deficits and infarct volume were significantly reduced. The best effective dose was 200mg/kg.(2)With the use of 200mg/kg DAS, SOD was increased, while MDA were decreased in injured brain tissue. Meawhile,both the expression of Nrf2 and NQO1 were increased.(3)With the use of 200mg/kg DAS, the number of TUNEL-positive cells were signifcantly reduced. meanwhile, the expression of Bcl-2 was increased, while the expression of caspase3 was decreased.Conclusion: (1)Pretreatment with DAS could protect brain from focal cerebral ischemia-reperfusion injury.(2) These results indicate that DAS protects brain from focal cerebral ischemia-reperfusion injury via activation of Nrf2/NQO1.(3)These results suggested that DAS could protect brain from ischemia-reperfusion injury, which at least, related to its anti-apoptotic effects in part.