Protective Effects Of Acutase On Focal Cerebral Ischemia-reperfusion Injury In Rats And Its Mechanisms

AIM To investigate the protective effects of acutase on local cerebral ischemia reperfusion injury in rats and possible mechanisms by an animal model of reversible middle cerebral artery occlusion (MCAO). METHODS Reversible middle cerebral artery occlusion (MCAO) model was produced by intraluminal suture technique. After 3h of occlusion and 24h of reperfusion, the extent of neurological deficits was evaluated by Longer' method; the infarction area of brain was measured by TTC staining technique; NO﹑MDA﹑MPO﹑iNOS and SOD level in brain tissue were measured; morphological changes of brain were observed and the expression of bFGF was measured. Acutase was administrated i.v. at different time respectively to study its protective effects and possible mechanisms. RESULTS (1) After 3h of occlusion and 24h of reperfusion, the neurological syndromes and the infarction area were showed, the activity of MPO and iNOS and the contents of NO and MDA increased, the change of brain histology were appeared and the expression of bFGF increased. (2) Both 2 and 4 U·Kg-1 doses of acutase administrated at the beginning of reperfusion can reduce neurological score and increase the ratio of PGI2/TXA2 in plasma comparing with ischemia-reperfusion group. In brain tissue of the occluded side, the infarction area and the activity of MPO was decreased by acutase in a dose-dependent manner. And the 4U·Kg-1 dose of acutase administrated at the beginning of reperfusion can also decrease the activity of iNOS from 2.11±0.53 to 1.17±0.51U·mg-1Pro, reduce the lever of NO from 17.68±6.57 to 10.06±4.39μmol·g-1Pro and reduce the content of MDA from 35.30±4.73 to 25.54±5.47 nmol·mg-1Pro. (3) The 4U·Kg-1 dose of acutase administrated at the beginning of ischemia has better effects on above factors comparing with that of reperfusion, it could reduce the activity of MPO from 0.216±0.046 to 0.092±0.040 U·g-1,decrease the lever of NO from 17.43±6.41 to 5.59±0.57μmol·g-1Pro, reduce the activity of iNOS from 2.10±0.77 to 0.58±0.23U·mg-1Pro and reduce the content of MDA from 34.57±3.47 to 18.79±4.99nmol·mg-1Pro. Besides these, it could alleviate the pathomorphologic changes , lighten the hurt of cerebrovascular endothelial cell and maintaine the structure of micro-vessels. It also had a significant increase of the expression of bFGF.CONCLUSIONS (1) Acutase could protect the focal cerebral ischemia reperfusion injury by inhibiting the inflammation reaction, reducing the activity of iNOS and lipid peroxides, increasing of the ratio of PGI2/TXA2, attenuating microvascular injury and enhancing bFGF expression. (2) The effect of administration of acutase at the beginning of occlusion is better than that of reperfusion, which prompted a great importance of its early administration.