不同脑缺血预处理时相对再次缺血损伤大鼠脑组织中IL-1β、TNF-α、IL-10含量的影响

Influences of cerebral ischemic preconditioning on content of brain IL-1β,TNF-α and IL-10 in rats with second cerebral ischemic lesion at different time points

目的观察脑缺血预处理(CIP)后24、72、120、168h4个不同的时间点再次缺血损伤大鼠脑组织中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)含量的变化趋势,探讨IL-1β、TNF-α、IL-10在脑缺血耐受中的作用。方法将大鼠随机分为6组:假手术组,缺血再灌注损伤组,CIP后24、72、120、168h再次损伤组。CIP各组先短暂阻断双侧颈总动脉10min作为缺血预处理,分别于缺血预处理后24、72、120、168h线栓法阻断大脑中动脉2h作为再次缺血损伤;缺血再灌注损伤组只阻断大脑中动脉2h;采用酶联免疫吸附试验(ELISA)测定各组大鼠脑组织匀浆中IL-1β、TNF-α、IL-10含量。结果与假手术组比较,缺血再灌注损伤组大鼠脑组织中IL-1β、TNF-α和IL-10含量均明显升高(P<0.05);与缺血再灌注损伤组比较,CIP后24、72h再次缺血损伤组IL-1β含量明显升高(P<0.05),120、168h再次缺血损伤组IL-1β含量逐渐降低;CIP后24、120h再次缺血损伤组TNF-α含量明显升高(P<0.05),72、168h再次缺血损伤组TNF-α含量呈降低趋势;CIP后24、72h再次缺血损伤组IL-10含量明显升高(P<0.01,P<0.05),120h再次缺血损伤组IL-10呈降低趋势,168h再次缺血损伤组IL-10又明显升高(P<0.05)。结论在CIP后24h脑组织中细胞因子IL-1β、TNF-α、IL-10水平明显升高能持续到72h(TNF-α除外),表明细胞因子作为触发物质,启动较早,刺激机体产生内源性的保护作用,对抗下次缺血带来的损伤,提高脑缺血耐受。

Objective To observe the change trend of content of brain interleukin-1β （IL-1β）, TNF-α and IL-10 in rats with second cerebral ischemic lesion at four time points （24 h, 72 h, 120 h and 168 h） after cerebral ischemic preconditioning （ CIP）, and to discuss the actions of IL-1β, TNF-α and IL-10 in cerebral ischemic tolerance. Methods All rats were randomly divided into 6 groups, including the sham-operation group, ischemia-reperfusion group, group of second lesion after CIP for 24 hours （24-h group）, 72 hours （72-h group）, 120 hours （120-h group） and 168 hours （168-h group）. All CIP groups were given CIP by the transient occlusion of bilateral carotid artery for 10 minutes, and after 24, 72, 120 and 168 hours the second ischemic lesion was induced by using suture method to obstruct the middle cerebral artery. In the ischemia-reperfusion group the middle cerebral artery was obstructed for only 2 hours. The content of brain IL-1β, TNF-α and IL-10 were detected by using ELISA in rats with the second ischemic lesion at four time points. Results Compared with the sham-operation group, the content of IL-1β, TNF-α and IL-10 increased significantly in the ischemia-repeffusion group （P 〈 0. 05）. The content of IL-1 β increased significantly in the 24-h group and 72-h group （P 〈0.05）, and decreased gradually in the 120-h group and 168-h group compared with the ischemia-repeffusion group. The content of TNF-α increased significantly in the 24-h group and 120-h group （ P 〈 0. 05 ）, and trended to reduce in the 72-h group and 168-h group. The content of IL-10 increased significantly in the 24-h group and 72-h group （ P 〈 0. 01, P 〈 0. 05 ）, and trended to reduce in the 120-h group but increased again in the 168-h group （P 〈 0. 05）. Conclusion After CIP for 24 hours, the content of brain cytokines, IL-1β, TNF-α and IL-10, increased significantly. As trigger substances influenced by C/P, cytokines activated earlier to stimulate the body having endogenous protective effects, resisting the lesion induced by the lesion induced by the second ischemia, and improving brain ischemic tolerance.