替格瑞洛对大鼠全脑缺血/再灌注损伤的神经保护作用

Neuroprotective effect of ticagrelor against global cerebral ischemia/reperfusion injury in rats

目的研究替格瑞洛对大鼠全脑缺血/再灌注损伤的神经保护作用。方法♂Wistar大鼠50只,随机分为假手术组、模型组、替格瑞洛低、中、高剂量组(37.5、75、150 mg·kg^(-1)),采用四血管阻断法建立大鼠全脑缺血模型,对大鼠再灌注2、24、48 h卒中指数和神经病学症状评分;HE和尼氏染色方法考察大鼠海马CA1区神经元病理损伤情况;采用比浊法测定二磷酸腺苷(adenosine diphosphate,ADP)诱导的3 min血小板最大聚集率,以及检测血浆凝血4项。结果与模型组比较,替格瑞洛低、中、高剂量组均降低24 h(P<0.05)和48 h(P<0.01)卒中指数,降低48 h神经病学评分(P<0.01),降低血小板聚集率(P<0.01),升高海马CA1区神经元数目(P<0. 01),替格瑞洛治疗明显改善海马CA1区神经元形态及数目。结论替格瑞洛对大鼠全脑缺血/再灌注损伤具有一定神经保护作用,可作为一种潜在的神经保护剂进行进一步研究。

Aim To research the neuroprotective effect of ticagrelor against global cerebral ischemia/reperfusion injury in rats.Methods Fifty adult male Wistar rats were randomly divided into five groups:sham-operation,vehicle,ticagrelor of 3 doses(37.5,75,150 mg·kg^-1,ig).The global cerebral ischemia was established with four-vessel occlusion.Apoplexy index and neurological symptoms were detected after reperfusion injury 2 h,24 h,48 h.HE staining and Nissl staining were applied to assess the neuronal injury after global cerebral ischemia/reperfusion injury in CA1 region of hippocampus.Platelet aggregation induced by ADP in rats was measured with turbidimetric method.Four items of coagulation were detected by automatic coagulation analyzer.Results Compared with vehicle,the low,medium and high doses of ticagrelor reduced the apoplexy index at 24h(P<0.05),48 h(P<0.01),and significantly reduced the neurological symptom at 48h(P<0.01),and could significantly reduce platelet aggregation of rats(P<0.01),the number of neurons in CA1 region of hippocampus was larger(P<0.01),and it also significantly protected the neurons in both number and morphology.Conclusions The ticagrelor possesses neuroprotective effect against global cerebral ischemia/reperfusion injury in rats,and it may be as a drug of neuroprotective agent in further study.