吗啡预处理对局灶性脑缺血大鼠脑保护作用的研究

Cerebral protective effects of morphine preconditioning against focal cerebral ischemia in rats

目的探讨吗啡预处理对整体动物脑局灶性缺血的早期保护作用,及其对大鼠血清S-100B蛋白的影响。方法 30只雄性Wistar大鼠,采用大脑中动脉线栓法建立局灶性脑缺血模型。随机将30只Wistar大鼠分为假手术组(S组)、脑缺血24 h组(Ⅰ组)和吗啡预处理后脑缺血24 h组(M组)。缺血前30 min,S、Ⅰ组大鼠腹腔注射0.9%氯化钠溶液2 mL,M组大鼠腹腔注射吗啡3 mg/kg(经2 mL0.9%氯化钠溶液稀释)预处理。缺血24 h后进行神经功能缺损评分,测定S-100B蛋白水平及脑梗死体积,并对大鼠石蜡脑片进行苏木精-伊红(H-E)染色观察缺血皮层的组织形态学变化。分别对两组的血清S-100B蛋白水平与神经功能缺损评分及脑梗死体积进行相关性分析。结果 S组无神经功能缺损表现,梗死灶的组织学形态正常。与S组相比,Ⅰ组、M组大鼠的神经功能评分均显著增高(P值均<0.05)。与Ⅰ组相比,M组大鼠的神经功能缺损评分、脑梗死体积百分率及血清S-100B蛋白的水平均显著降低(P值均<0.05),缺血大脑皮层的组织形态学损伤减轻。I、M组的血清S-100B蛋白水平与神经功能缺损评分及脑梗死体积均有较好的相关性(P值均<0.05)。结论 3 mg/kg吗啡预处理可产生早期相脑保护作用,并显著降低血清S-100B蛋白水平。血清S-100B蛋白与脑缺血后脑损伤的程度呈正相关,可作为评价吗啡脑保护作用的血清标记物。

Objective To investigate the cerebral protective effects of morphine preconditioning（MP） on focal cerebral ischemia in rats.Methods Thirty healthy male Wistar rats were randomly divided into three groups：sham operation group（S group）,middle cerebral artery occlusion group（MCAO,I group） and MP combined MCAO group（M group）.Rats in I and M groups received left MCAO by intraluminal suturing.Thirty minutes before ischemia,all rats were injected with normal saline（2 mL） intraperitonealkt,and morphine 3 mg/kg （2 mL diluted with normal saline） was used in M group via intraperitoneal injection.Focal cerebral ischemia was performed for 24 hours and at the end of ischemia the infarction volumes,serum S-100B protein and neurologic deficit scores were evaluated separately.Hematoxylin and eosin staining for the cerebral tissue was performed. The correlation of serum S-100B protein levels with neurological deficit scores and infarction volumes was analyzed by SPSS.Results There were no neurological deficits and cerebral infarctions in rats of S group.Their histological morphology results were also normal.However,the neurological deficit scores were higher in rats of group I and group M compared with those in S group.Rats exposed to morphine（3 mg/kg,at 30 min before MCAO） had smaller infarction volumes,lower serum S-100B levels,better neurologic deficit scores and histological outcome than those in I group（P0.05）.The levels of serum S-100B protein had a significant linear correlation with neurological deficit scores and infarction volumes in I and M groups（P0.05）.Conclusion Morphine preconditioning（3 mg/kg intraperitoneal injection） can attenuate MCAO-induced ischemic injuries in an early-phase and significantly reduce the levels of serum S-100B protein in rats.The levels of serum S-100B protein is related to the extent of brain damage following cerebral ischemia,indicating that serum S-100B can be used as a biomarker for predicating the extent of neuron injury and neuro-protection.