ND308抗脑缺血神经保护作用探究.docVIP

ND308抗脑缺血神经保护作用探究 　 作者：谭君 梁绪国 严鹏 田京伟 【摘要】 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(Pgt;0.05),其余各组与模型组相比Plt;0.05或Plt;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。 【关键词】 ND308;脑缺血再灌注;炎症反应;核因子κB 　　【Abstract】 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 (Pgt;0.05 vs model group). Other groups showed significant difference (Plt;0.05 or Plt;0.01 vs model group).Conclusion ND308 may have protective effects on focal cerebral ischemic reperfusion injury through antiinflammatory effect. 　　【Key words】 ND308，ischemiareperfusion，inflammatory reaction，NFκB 　　丹参为唇形科植物丹参(Saluia miltiorrhiza Bge) 的干燥根及根茎，其制剂丹参片、丹参注射液在临床上