缝隙连接阻断剂辛醇对大鼠脑缺血再灌注后核转录因子κB通路的影响

Effect of gap junction blocker octanol on NF-κB pathway in rats following cerebral ischemia/reperfusion

目的探讨缝隙连接阻断剂辛醇对大鼠脑缺血再灌注后NF-κB通路的影响。方法选择健康雄性SD大鼠72只随机分为假手术组、对照组、DMSO组和辛醇组,每组18只,于建立脑缺血模型前30min,辛醇组腹腔注射辛醇溶液,对照组及假手术组腹腔注射等量生理盐水,DMSO组腹腔注射等量5%DMSO溶液。采用改良的神经功能缺损评分(mNSS)进行行为学评估,检测各组脑组织含水量、脑梗死体积,Western blot检测P65、磷酸化P65、ⅠκB-α、磷酸化ⅠκB-α蛋白表达。结果假手术组无脑梗死灶。与假手术组比较,辛醇组、对照组及DMSO组脑组织含水量、mNSS及脑梗死体积明显增加(P<0.05),且对照组和DMSO组磷酸化P65和磷酸化IκB-α蛋白表达明显增加,P65和IκB-α蛋白表达明显降低(P<0.05)。辛醇组mNSS、脑组织含水量、脑梗死体积、磷酸化P65和磷酸化IκB-α蛋白表达明显低于对照组和DMSO组;辛醇组P65和IκB-α蛋白表达明显高于对照组和DMSO组(72.13±2.01 vs 50.39±1.83、49.97±1.92,68.24±2.23 vs 43.45±1.53、42.56±1.48,P<0.05)。对照组与DMSO组mNSS、脑组织含水量、脑梗死体积、P65和磷酸化P65蛋白表达、ⅠκB-α和磷酸化IκB-α蛋白表达比较,无统计学差异(P>0.05)。结论缝隙连接阻断剂辛醇能减轻缺血再灌注损伤,机制可能与调节NF-κB信号通路有关。

Objective To study the effect of gap junction blocker octanol on NF-κB pathway in rats following cerebral ischemia/reperfusion(I/R).Methods Seventy-two healthy male SD rats were randomly divided into sham operation group,control group,DMSO group and octanol group(18 in each group).The rats in octanol group received intraperitoneal solution injection of octanol,those in control group and sham operation group received intraperitoneal injection of normal saline,and those in DMSO group received intraperitoneal injection of 5% DMSO solution at 30 min before the I/R injury model was established.The behaviors were assessed according to their modified neurological defect scale score(mNSS),the water content in brain tissue and size of cerebral infarction in rats of different groups were measured,the expressions of P65,p-P65,IκB-αand p-IκB-αwere detected by Western blot.Results No cerebral infarction was found in sham operation group.The water content in brain tissue and mNSS were significantly higher and the size of cerebral infarction was significantly larger in octanol group,control group,DMSO group than in sham operation group(P<0.05).The expression levels of p-P65 and p-IκB-αprotein were significantly higher while those of P65 and IκB-αprotein were significantly lower in control group and DMSO group than in sham operation group(P<0.05).The mNSS and water content in brain tissue were significantly higher,the size of cerebral infarction was significantly larger,the expression levels of p-P65 and p-IκB-αprotein were significantly lower while the expression levels of P65 and IκB-αprotein were significantly higher in octanol group than in control group and DMSO group(72.13±2.01 vs 50.39±1.83、49.97±1.92,68.24±2.23 vs 43.45±1.53、42.56±1.48,P<0.05).No significant difference was detected in mNSS,water content in brain tissue,size of cerebral infarction,expressions of P65,p-P65,IκB-αand p-IκB-αprotein between control group and DMSO group(P>0.05).Conclusion The gap junction blocker octanol can reduce I/R injury by regulating the NF-κB signaling pathway in rats following cerebral I/R.