| Allicin (diallyl thiosulfinate) is a highly active component in extracts of garlic. Several reports have revealed the antithrombosis and antiplatelet aggregation effects of allicin. In this study, we design to investigate its mechanism, effective doses, and effective treatment time-window on focal cerebral ischemia-reperfusion injury (CIRI) in rats.In the improved model, right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 2 h, and then reperfused for 24 h or 48 h. 10 mg · kg-1 and 20 mg · kg-1 doses of allicin were administrated i.v. at different time respectively to study its protective effects and possible mechanisms. 20 mg · kg-1 dose of allicin was administrated i.v. at the beginning of ischemia, reperfusion Oh, reperfusion 2h respectively. The effects on reperfusion 24h were measured. The protective effects of allicin on remote-organs injury were also studied.RESULTS:1.The improved MCAO model is better than Longa model in stability, reliability and reproducibility; and has a higher achievement ratio.2.The protective effects and its mechanism of allicin on CIRI rats for 24 h(1) With the use of 10 mg. kg-1 and 20 mg · kg-1 doses of allicin, mortality, brain injured area, cerebral edema of occluded side, and neurological deficits were dramatically reduced. The morphologe was improved. 20 mg · kg-1 doses of allicin is more effective.(2) With the use of 10 mg · kg-1 and 20 mg · kg-1 doses of allicin, SOD was increased, MDA and MPO were decreased in injured brain tissue; the contents of NO, iNOS, and iNOSmRNA in injured brain tissue were decreased, and it is dosage-dependent; ET in plasma was decreased; the ratio of prostacyclin (PGI2)/thromboxane (TXA2) in plasma was increased. The numbers of apoptotic cells were dramatically reduced in the group of 20 mg · kg-1 doses of allicin. No significant effect on calcineurin (CaN) content was discovered.3.The protective effects and its mechanism of allicin with different treatment time-window on CIRI rats for 24h(1) The injured area of brain, mortality and neurological deficits in the three groups were dramatically reduced by allicin. No significant difference was discovered among the three groups. The cerebral edema of occluded side in the three groups were also dramatically reduced by allicin, but that was more serious in the group of treatment at reperfusion 0 h and at reperfusion 2 h than that at the beginning of ischemia. The morphology was improved by 20 mg · kg-1 dose of allicin, but that in the ischemic 0 h group was the best in the three groups.(2) The contents of NO and iNOS in the injured brain tissue were decreased in the ischemic 0 h group and the reperfusion 0 h group. No significant effect in the reperfusion 2 h group on NO and iNOS content was discovered.4. The protective effects and its mechanism of allicin with different reperfusion time-point on CIRI rats(1) Compared with CIRI 48 h, the brain injured area was reduced and the morphology of the occluded area was improved, no significant difference in cerebral edema of occluded side and neurological deficits was discovered on CIRI rats for 24 h. With the use of 10 mg·kg-1 and 20 mg ·kg-1 doses of allicin, the brain injured area, mortality, cerebral edema of occluded side, and neurological deficits were dramatically reduced, the morphology of the occluded area was improved.(2) Compared with CIRI 48 h, the numbers of apoptotic cells were less in the group of reperfusion 24h. CaN activity was increased on CIRI rats for 48h. The numbers of apoptotic cells were dramatically reduced in the group of 20 mg · kg-1 doses of allicin , the ratio of bcl-2/bax in injured brain tissue was increased. CaN activity was inhibited by two doses of allicin.5. The protective effects of allicin on remote-organs with CIRI rats(1) With the use of 10 mg · kg-1 and 20 mg · kg-1 doses of allicin, morphologic changes of heart, lung, liver and kidney were dramatically improved.Results show that: (1) The neuroprotective effects of 10 mg · kg-1 and 20 mg · kg-1 doses of allicin on CIRI rats might be attributed to its effects of reducing lipid peroxides, attenuting inflammation, depressing expression of iNOSmRNA. The anti-apoptosis effect of 20 mg ·kg-1 dose of allicin is suppression of the expression of bax. (2) It is the best treatment time-point to administrate allicin at ischemic onset. (3) The injured degree at CIRI 48 h was more serious than that of at CIRI 24 h. The significant neuroprotective effects of 10 mg · kg-1 and 20 mg · kg-1 doses of allicin were discovered on CIRI rats for 48 h. The activity of CaN was increased during CIRI 48 h, and two doses of allicin inhibited it effectively. (4) The significant protective effects on remote-organs injury of 10mg · kg-1 and 2 0 mg · kg-1 doses of allicin were discovered.
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