缝隙连接阻滞剂辛醇对大鼠脑缺血再灌注损伤的神经保护作用可能与减轻炎症反应有关

Neuroprotective effects of gap junction blocker octanol on cerebral ischemia-reperfusion injuiy in rats may be associated with the alleviation of inflammatory response

目的探讨缝隙连接阻断剂辛醇对大鼠缺血再灌注后促炎性细胞因子水平的影响。方法72只雄性SD大鼠随机分为假手术组、生理盐水对照组、赋形剂组和辛醇干预组,每组18只。应用改良线栓法制备短暂性大脑中动脉闭塞模型,辛醇干预组于缺血前30 min按5 mmol/kg体重腹腔注射辛醇溶液,生理盐水对照组和赋形剂组分别在术前30 min腹腔注射等量生理盐水和5%二甲基亚砜溶液。在缺血2 h再灌注24 h后检测各组神经功能缺损评分、脑组织含水量和脑梗死体积,应用酶联免疫吸附法检测各组血清白细胞介素(interleukin,IL)-1β、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量。结果与生理盐水对照组和赋形剂组相比,辛醇干预组神经功能缺损评分显著降低(P均<0.05),脑组织含水量显著降低(P<0.05),脑梗死体积显著缩小(P<0.05),而且IL-1β、IL-6和TNF-α表达水平均显著降低(P均<0.05)。生理盐水对照组神经功能缺损评分、脑组织含水量、脑梗死体积以及血清IL-1β、IL-6和TNF-α含量与赋形剂组均差异无统计学意义。结论缝隙连接阻断剂辛醇能减轻脑缺血再灌注损伤,其机制可能与减轻炎症反应有关。

Objective To investigate the effects of octanol,a gap junction blocker,on the levels of pro-inflammatory cytokines after cerebral ischemia-reperfusion in rats.Methods Seventy-two male SD rats were randomly divided into sham operation group,saline control group,vehicle group,and octanol intervention group(n=18 in each group).The model of transient middle cerebral artery occlusion was induced by the modified suture method.The octanol intervention group was intraperitoneally injected with octanol solution at 5 mmol/kg body weight 30 min before ischemia.The saline control group and the vehicle group were intraperitoneally injected with the same amount of physiological saline and 5%dimethyl sulfoxide solution 30 min before procedure.The neurological deficit score,brain water content,and cerebral infarction volume in each group were detected after ischemia for 2 h and reperfusion for 24 h.Enzyme-linked immunosorbent assay was used to detect the serum interleukin(IL)-1β,IL-6,and tumor necrosis factor-α(TNF-α)levels.Results Compared with the saline control group and the vehicle group,the neurological deficit score of the octanol intervention group was significantly lower(all P<0.05),the brain tissue water content was significantly decreased(P<0.05),the cerebral infarction volume was significantly reduced(P<0.05),and the expression levels of IL-1β,IL-6,and TNF-αwere significantly decreased(all P<0.05).There were no significant differences in neurological deficit score,brain water content,cerebral infarction volume and serum IL-1β,IL-6 and TNF-αlevels between the saline control group and the vehicle group.Conclusion Gap junction blocker octanol can reduce cerebral ischemic-reperfusion injury.Its mechanism may be related to the alleviation of inflammatory response.