ND-308抗脑缺血神经保护作用的研究

Neuroprotective effects of ND-308 on focal cerebral ischemia in rats

目的观察ND-308对大鼠局灶性脑缺血的保护作用,探讨ND-308抗脑缺血作用的机制。方法78只健康雄性SD大鼠,采用大脑中动脉线栓法建立局灶性脑缺血再灌注(Ischemia/Reperfusion)模型,随机分为6组:模型组、假手术组、ND-308小剂量组(5 mg/kg)、ND-308中剂量组(10 mg/kg)、ND-308大剂量组(20 mg/kg),阳性对照依达拉奉组(6 mg/kg),于再灌注后30 min内尾静脉注射给药。缺血2 h再灌注24 h后测定神经行为障碍评分、脑梗死体积,HE染色观察缺血皮层组织形态学变化,采用免疫组织化学染色法测定IL-1β、TNF-α、NF-κB的表达。结果ND-308治疗组与模型组相比神经系统症状减轻,脑梗死体积缩小,下调脑组织中IL-1β、TNF-α、NF-κB的表达,并呈现一定剂量依赖性,ND-308小剂量组各项与模型组相比无统计学意义(P>0.05),其余各组与模型组相比P<0.05或P<0.01。结论ND-308对脑缺血再灌注具有保护作用作该作用可能有抑制炎症反应有关。

Objective To investigate the neuroprotective effects of ND-308 against focal cerebral ischemia in rats, and to discuss the possible mechanism. Methods A rat model of focal cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion using modified filament method. A total of 78 healthy male SD rats with MCAO were randomly and equally divided into six groups： sham control group,model group,ND-308 treated groups （5 mg,10 mg and 20 mg/kg ） ,positive control edalavone group （6 mg/kg）. All drugs were administered via tail vein injection within 30 min after reperfusion. After 2 h ischemia followed 24 h reperfusion the neurological deficits and the sizes of cerebral infarction were measured. Immunohistochemistry was used to detect the expression of TNF-α, IL-1β and NF-κB proteins. Results ND-308 could decrease the neurological deficits and the sizes of cerebral infarction and also down regulate the expression of TNF-α, IL-1β and NF-κB proteins in a dose-dependent manner. ND-308 low-dose group showed no statistical significance （ P 〉 0. 05 vs model group ）. Other groups showed significant difference （ P 〈 0. 05 or P 〈 0. 01 vs model group）. Conclusion ND-308 may have protective effects on focal cerebral ischemic reperfusion injury through anti-inflammatory effect.