不同剂量纳洛酮后处理对大鼠局灶性脑缺血再灌注损伤的影响

Effect of different doses of naloxone postcondittoning on focal cerebral ischemia-reperfusion injury in rats

目的探讨不同剂量纳洛酮后处理对大鼠局灶性脑缺血再灌注损伤的影响。方法成年SD大鼠88只，体重270～330g，随机分为4组（n=22）：假手术组（S组）、脑缺血再灌注组（IR组）和不同剂量纳洛酮后处理组（N1,2组）。除S组外，其它3组均采用阻断右侧大脑中动脉90min、再灌注24h的方法制备局灶性脑缺血再灌注损伤模型。NJ1,2组于再灌注即刻分别腹腔注射纳洛酮1、10mg／kg，S组和IR组给予等容量生理盐水。分别于再灌注2、24h时测定大鼠神经功能障碍评分（NDS）；再灌注24h时测定脑梗死面积和脑组织微管相关蛋白2（MAP2）的表达水平和脑组织血浆容量、微血管直径和长度。结果与S组相比，IR组、N1,2组NDS评分均升高，脑梗死面积增大，脑组织MAP2表达水平下调，缺血侧脑组织血浆容量降低，微血管直径和长度减小（P〈0．05）；与IR组相比，N2组NDS评分降低，脑梗死面积减小，脑组织MAP2表达水平上调，缺血侧脑组织血浆容量升高，微血管直径和长度增大（P〈0．05），N，组上述指标差异无统计学意义（P〉0．05）；与N1组相比，N2组NDS评分降低，脑梗死面积减小，脑组织MAP2表达水平上调，缺血侧脑组织血浆容量升高，微血管直径和长度增大（P〈0．05）。结论纳洛酮后处理可减轻大鼠局灶性脑缺血再灌注损伤，且呈剂量依赖性。

Objective To investigate whether naloxone postconditioning could attenuate the focal cerebral iscbemia-reperfusion （I/R） injury in rats. Methods Eighty-eight adult male SD rats weighing 270-330 g were randomly divided into 4 groups （n = 22 each）： group I sham operation （S）; group II I/R; group III, IV I/R ＋ low and high dose naloxone （N1, N2 ）. Focal cerebral I/R was produced by occlusion of right middle cerebral artery for 90 rain followed by 24 h reperfusion. In group N1 and N2 naloxone 1 and 10 mg/kg were injected intraperitoneally at initiation of reperfusion respectively. In group I/R normal saline was injected instead of naloxone. HR, MAP and EKG were continuously monitored throughout the experiment. The neurological deficits were scored （0 = no deficit, 4 = unable to crawl, mental dysfunction） at 2 h and 24 h of reperfusion. The animals were then decapitated. The brains were immediately removed for determination of infarct size （ n = 10） and the expression of microtubule-associated protein-2 （MAP-2） in brain tissue （n = 6）. In the other 6 rats in each group FICT-dextran 1 ml （50 mg/ml） was injected iv at 1 rain before decapitation. The cerebral plasma volume and diameter and segment length of cerebral microvessels on the I/R side were measured using laser scanning confocal microscopy （LSCM）. Results Focal cerebral I/R significantly increased neurological deficit scores, induced cerebral infarct, and decreased MAP-2 expression in the brain tissue, cerebral plasma volume and the diameter and segment length of cerebral microvessels on the I/R side. Postconditioning with 10 mg/kg naloxone significantly attenuated the above-mentioned focal cerebral I/R-induced changes. Conclusion Postconditioning with naloxone can attenuate focal cerebral I/R injury in a dose-dependent manner.