Protective Effects Of Melatonin On Cerebral Ischemia-Reperfusion Injury And Its Mechanism

The model of cerebral ishemia-2 h/reperfusion-24 h was induced by middle cerebral artery occlusion (MCAO) with the intraluminal suture occlusion technique in SD rats. Melatonin (MT) 10,20 mg.Kg-1 was administered (ip) four times in an animal: at 0 h, 1 h, 2 h, 6 h of reperfusion. After 24 h reperfusion, the protective effects of MT on cerebral ischemia reperfusion injury (CIRI), its mechanism and the protective effect of MT on remote -organ injury were studied.Results:(l) With the use of MT10, 20 mg.Kg-1, the neurological score was significantly improved; brain infarct area and edema degree were reduced; the morphology of cortex and subcortex was also improved; MT20 mg.kg-1 helped to increase the content of adenosine 5'-triphosphate (ATP) in brain tissue. (2)MT 10, 20 mg.Kg-1 reduced the content of MDA in brain tissue, and protected the activity of SOD in brain tissue. (3) MT 20 mg.kg-1 attenuated the disequilibrium of TXA2 /PGk in plasma and inhibited the increase of MPO in brain tissue. (4) MT 10- 20 mg.Kg-1 decreased the content of ET in plasma. (5) MT 20 mg.kg-1 inhibited the apotosis of neurocytes. (6) Morphological alterations of heart, lung, liver and kidney were greatly attenuated by MT 20 mg.kg-1.These results above demonstrate that (1) MT is an effective agent against CIRI. (2) The protective effects of MT on CIRI may be related to its anti-inflammation and anti-oxidation properties as well as its effect on the decrease of ET and the inhibition of neurocyte apotosis. (3) The attenuation of the remote-organ injury is another aspect of its protective effects.