吡拉格雷钠对脑缺血再灌注损伤模型大鼠神经功能的改善作用及机制研究

目的:研究吡拉格雷钠对脑缺血再灌注损伤模型大鼠神经功能的改善作用及相关机制。方法:将72只SD大鼠随机分为假手术组、模型组、阳性对照组(地佐环平0.8 mg/kg)和吡拉格雷钠低、中、高剂量组(20、30、45 mg/kg),每组12只。除假手术组大鼠行假手术外,其余各组大鼠均采用大脑中动脉结扎诱导脑缺血再灌注损伤模型。术后2 h尾静脉注射相应药物,假手术组和模型组大鼠注射等量生理盐水,连续给药6 d,给药间隔均为24 h。再灌注24 h和末次给药后,评估大鼠的神经功能缺陷评分和姿势反射评分,采用微正电子发射断层扫描评估脑损伤情况(包括全脑、岛状皮层、壳核、纹状体、体细胞皮层、杏仁核、运动皮层)。然后处死大鼠,2,3,5-氯化三苯基四氮唑(TTC)染色后观察脑梗死情况并计算脑梗死体积,酶联免疫吸附试验检测其脑组织中Na^+-K^+-ATP酶、Ca²⁺-ATP酶活性和谷氨酸(Glu)含量。结果:与假手术组比较,模型组大鼠缺血再灌注后24 h和末次给药后的神经功能缺陷评分、姿势反射评分均明显升高(P<0.05或P<0.01),脑缺血再灌注24 h与末次给药后脑组织的SUV、全脑及各不同脑区的右左脑SUV比值均明显降低(P<0.01);末次给药后脑梗死体积百分数明显升高(P<0.01),脑组织中Na^+-K^+-ATP酶和Ca²⁺-ATP酶活性明显降低(P<0.01),Glu含量明显升高(P<0.01)。与模型组比较,吡拉格雷钠低、中、高剂量组和阳性对照组大鼠上述指标均明显改善(P<0.05或P<0.01)。结论:吡拉格雷钠对大鼠脑缺血再灌注损伤和神经功能有改善作用,这可能与上调脑组织中Na^+-K^+-ATP酶和Ca²⁺-ATP酶活性和下调Glu含量有关。

Improvement Effects and Mechanism Study of Pyragrel Sodium on Cerebral Ischemia-reperfusion Injury in Rats

OBJECTIVE:To study the improvement effect and related mechanism of pyragrel sodium on nerve function of cerebral ischemia-reperfusion injury model rats.METHODS:Totally 72 SD rats were randomly divided into sham operation group,model group,positive control group(dizocilpine 0.8 mg/kg),pyragrel sodium low-dose,medium-dose and high-dose groups(20,30,45 mg/kg),with 12 rats in each group.Except sham operation group received sham operation,rats in the other groups were treated with middle cerebral artery ligation to induce cerebral ischemia-reperfusion injury model.The rats in the sham operation group and the model group were injected with the constant volume of normal saline,for consecutive 6 d,and the interval of administration was 24 hours.After 24 h reperfusion and last medication,neurological deficit score and postural reflex score in rats were evaluated.The situation of cerebral injury(including whole brain,insular cortex,putamen,striatum,somatic cortex,amygdala,motor cortex)was evaluated by using micropositron emission tomography.The rats were sacrificed,and the situation of cerebral infarction was observed by TTC and cerebral infarction volume was calculated.Na^+-K^+-ATPase,Ca^2+-ATPase activity and Glu content were detected by ELISA.RESULTS:Compared with sham operation group,neurological deficit score and postural reflex score increased significantly in model group 24 h after ischemia-reperfusion and after last medication(P<0.05 or P<0.01).After 24 hours of cerebral ischemia-reperfusion and the last medication,SUV of brain tissue,SUV ratio of right left brain of different cerebral areas were decreased significantly(P<0.01).After last medication,the percentage of cerebral infarction volume was increased significantly(P<0.01);the activities of Na^+-K^+-ATPase and Ca^2+-ATPase were decreased significantly(P<0.01),while Glu content was increased significantly(P<0.01).Compared with model group,above indexes of pyragrel sodium low-dose,medium-dose and high-dose group,positive control group were all improved significantly(P<0.05 or P<0.01).CONCLUSIONS:Pyragrel sodium can improve cerebral ischemia-reperfusion injury and nerve function,which is related to the activity up-regulation of Na^+-K^+-ATPase and Ca^2+-ATPase,the down-regulation of Glu content.