氯胺酮预处理对大鼠局灶性脑缺血/再灌注损伤后脑水肿和水通道蛋白4表达的影响

The effects of ketamine pretreated on cerebral edema and AQP4 expression after transient focal cerebral ischemia/reperfusion in rats

目的 观察氯胺酮缺血前预给药对大鼠短暂性脑缺血/再灌注损伤后神经缺失症状、脑水肿及Aquaporin 4（AQP4）表达的影响.方法 62只健康雄性Sprague-Dawley大鼠,体重220～250 g,随机分为假手术组（Sham组,n=18只）、生理盐水组（Vehicle组,n=22只）和氯胺酮预处理组（Ketamine组,n=22只）.Vehicle组、Ketamine组大鼠采用线栓法阻塞大鼠右侧大脑中动脉,90 min后拔出栓线实现再灌注,建立局灶性脑缺血/再灌注模型.Ketamine组、Vehicle组分别于缺血前30min静脉持续输注（1mg·kg-1·min-1）5%氯胺酮及0.9%生理盐水,30 min后实施缺血再灌注损伤.Sham组手术操作同前,但线栓未阻塞大脑中动脉.再灌注24 h大鼠进行神经缺失症状评分,后断头取脑,采用干湿重法测定缺血侧脑半球的水肿度,Western-blot检测缺血周边区脑组织AQP4表达.结果 Vehicle组、Ketamine组大鼠脑缺血/再灌注损伤后神经功能缺失症状明显,缺血侧脑半球干湿重比值较Sham组明显增加（P〈0.01）;与Vehicle组相比,Ketamine组缺血侧脑半球干湿重比值无明显减小（P〉0.05）.与Sham组相比,Vehicle组、Ketamine组大鼠脑缺血/再灌注损伤后缺血周边区AQP4表达明显上调（P〈0.01）;与Vehicle组相比,Ketamine组AQP4表达无明显下调（P〉0.05）.结论 大鼠脑缺血/再灌注损伤后神经功能缺失症状及脑水肿明显,缺血周边区脑组织AQP4表达上调;氯胺酮缺血前预处理未能明显改善神经缺失症状及脑水肿,对缺血周边区脑组织AQP4的表达无影响.

Objective To investigate the effects of ketamine pretreatment on cerebral edema following brain ischemia reperfusion injury in rats and assess the involvement of Aquaporin 4（AQP4） expression.Methods Sixty-two healthy male Sprague-Dawley rats weighing 220-250 g were randomly divided into 3 groups：sham operation group（group Sham,n=18）;saline group（group Vehicle,n=22）;ketamine pretreatment group（group Ketamine,n=22）.The transient focal ischemia/reperfusion was induced by introducing a silicone-coated monofilament nylon suture from the right external carotid artery into the origin of the middle cerebral artery,removing it after 90 min.In group Ketamine,the rats were exposed to ketamine（5％,1 mg·kg-1·min-1）for 30 vain before suffered from cerebral ischemia.Similarly;in group Vehicle and group Sham,the animals received saline vehicle at the same time and infusion rate.After the neurologic exams were assessed at 24 h of reperfusion,the rats were sacrificed after anesthetized,and the brains were quickly removed.To estimate cerebral edema,the wet-dry ratio was measured.Western-blot was used to detect the expression of AQP4 in the border of the infarct region Results The neurologic function deficit was significantly serious in group Vehicle and group Ketamine compared to group Sham（P〈0.01）.Ketamine pretreatment tended to improve neurologic outcome,but there was no statistical significance.The wet-dry weight ratio and AQP4 expression increased significandy in group Vehicle and group Ketamine Ⅲ than those in group Sham（P〈0.01）.Compared with saline vehicle,ketamine pretreatment did not decreased the wet-dry weight ratio significantly.AQP4 expression in group Ketamine was not significantly different from group Vehicle.Conclusion Ketamine pretreatment did not seem to improve the neurologic deficit outcome and attenuate edema,which was involved in no change of AQP4 expression.