| Objectives:According to the right middle cerebral artery occlusion-reperfusion model that was made by reforming Longa method, to simulate the pathophysiological process of acute cerebral ischemia reperfusion injury in human body. Investigating the effect of different treatments(preconditioning, post-conditioning and preconditioning united post-conditioning) of dexmedetomidine hydrochloride(Dex) on focal cerebral ischemia-reperfusion injury in rats. By evaluating the change difference of neurological deficit scores and brain infarct volume percentage in rat models, detecting superoxide dismutase (SOD) activity and malonaldehyde (MDA) content in brain tissue, and measuring neuronspeciflc enolase (NSE) content in serum. From the entirety, neurological deficit behavioral, partial histopathology and molecular level to discuss the different effect of Dex on focal cerebral ischemia-reperfusion injury in rats, and to infer the possible mechanism of it. Then to offer a clear and effective therapeutic method and a certain reference to the cerebral vascular disease patients and the cerebral ischemia high-risk patients during perioperative period. Methods:40 healthy male SD rats, aged 49-63 days, weighing 250-300g,were used in this study.40 rats were divided into 5 groups randomly:the sham operation group(Sham);the cerebral ischemic-reperfusion group(I/R);the dexmedetomidine hydrochloride preconditioning group(Dexl); the dexmedetomidine hydrochloride post-conditioning group(Dex2) and the dexmedetomidine hydrochloride preconditioning united post-conditioning group(Dex3),8 rats in each group. The right middle cerebral artery occlusion-reperfusion model was made by reforming Longa method.30 minutes before the sham operation, the sham group was received an injection of saline 5ml-kg-1 by peritoneal injection,8 hours after the sham operation, then received the same injection amount of saline. All rats were observed for another 19 hours.30 minutes before surgery, both I/R and Dex2 groups were received an injection of saline 5ml-kg-l by peritoneal injection. Then the right middle cerebral artery occlusion-reperfusion model was made.3 hours after artery occlusion and 5 hours after reperfusion, then the I/R group was received an injection of saline 5ml-kg-1 by peritoneal injection while the Dex2 group was treated with Dex 50ug-kg-1.Each group was accepted reperfusion for 24 hours.30 minutes before surgery, both Dex1 group and Dex3 groups were received an injection of Dex 50ug-kg-1 by peritoneal injection. Then the right middle cerebral artery occlusion-reperfusion model was made.3 hours after artery occlusion and 5 hours after reperfusion, then the Dex1 group was received an injection of saline 5ml-kg-1 by peritoneal injection while the Dex3 group was treated with Dex 50?g·kg-1.Each group was accepted reperfusion for 24 hours.27 hours after reperfusion, the neurological deficit scores were counted for each group. The brain infarct volume percentage of cerebral infarction size was evaluated by computer image processing system after stained by 2,3,5-triphenyltetrazolium chloride(TTC). The superoxide dismutase (SOD) activity and malonaldehyde (MDA) content in brain tissue, and the neuron specific enolase (NSE) content in serum were measured by Elisa method. Result:1. Each group of SD rats' differences in weight and age were not statistically significant(P>0.05); 2.Compared with the Sham group,in the I/R group, Dexl group, Dex2 group and Dex3 group, the score of NDS was decreased significantly, BIVP was increased obviously, the activity of SOD in brain tissue was significantly decreased, MDA content in brain tissue was increased significantly, and the content of serum NSE was obviously increased (P<0.05).3. Compared with I/R group, in the Dexl group and the Dex3 group which had been dealt with dexmedetomidine hydrochloride, the score of NDS was obviously reduced and the BIVP was decreased significantly (P<0.05); in these three groups which were treated by dexmedetomidine hydrochloride in different ways, the SOD activity was significantly increased, MDA content was significantly decreased and the content of serum NSE was significantly reduced (P<0.05); Between I/R group and Dex2 group the score of NDS and BIVP had no significant difference (P>0.05);4. Compared in these three groups which were treated by dexmedetomidine hydrochloride in different ways, both of the NDS scores in group Dexl and Dex3 were significantly lower than that in Dex2 group (P<0.05),and the MDA content in cerebral tissue as well as serum NSE content reduced significantly compared with Dex2 group (P<0.05); in Dex3 group,the content of serum NSE and MDA of brain tissue was significantly lower than that of group Dexl (P<0.05). The activity of SOD in brain tissue in Dex3 group was significantly higher than that in Dex2 group (P<0.05);but there were no obviously difference in BIVP in these three groups. Between Dexl group and Dex3 group the NDS score and SOD activity showed no significant difference (P>0.05). Between Dexl group and Dex2 group the SOD activity showed no significant difference too(P>0.05). Conclusion:1.According to the right middle cerebral artery occlusion-reperfusion model that was made by reforming Longa method, different treatments of dexmedetomidine hydrochloride all could reduce focal cerebral ischemia-reperfusion injury in rats.2. Dexmedetomidine hydrochloride preconditioning combined with post-conditioning could produce a better protective effect in the cerebral ischemia reperfusion injury.3. By inhibiting excessive oxidative stress response,reducing oxygen free radicals excessive producing may be one of the protective mechanisms on the cerebral ischemia reperfusion injury of Dexmedetomidine hydrochloride. |
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