摘要
目的 探讨蛋白激酶C (PKC)和核因子 κB (NF κB)在实验性脑血管痉挛中表达变化及PKC抑制剂对其影响。方法 中国白兔 75只 ,体重 1 5～ 2 0kg ,其中 6 0只采用枕大池二次注血法制成脑血管痉挛模型 ,随机分为单纯注血组 ( 15只 ) ,给药组 ( 30只 )和生理盐水组 ( 15只 ) ,其余 15只为假穿刺组。应用免疫组化、底物磷酸化激酶测定法、免疫印迹及EMSA等方法分别测定 4d ,7d和 10d不同时间基底动脉PKC和NF κB活性表达变化 ,并观察形态学改变。结果 单纯注血组较假穿刺组有明显变化 ,包括管腔狭窄、炎性浸润等 ,PKC及NF κB的活性表达明显增高且呈正相关 ,7天时最明显 ;给药组与单纯注血组比较 ,管腔狭窄和炎性浸润程度明显减轻 ,PKC和NF κB活性表达同时显著下降 ,且 10 0 μg/kg较 5 0 μg/kg作用更显著 ;生理盐水组较单纯注血组无明显变化。 结论 PKC和NF κB的异常激活在脑血管痉挛的形成中有重要意义 ,PKC抑制剂能显著改善实验性脑血管痉挛的程度及其炎性改变 ,其作用可能是通过同时抑制PKC及NF κB实现的。
Objective To evaluate the activity changes of PKC, NF-κB and the effect of PKC inhibitor on expression of PKC and NF-κB in cerebral vasospasm model in rabbits. Motheds 75 Chinese white rabbits, weighing between 1.5～2.0kg, were used in this study.Twice-hemorrage model of cerebral vasospasm was constructed in 60 rabbits, and then were randomly divided into three groups including Simply injecting blood group ( n =15), PKC inhibitor group ( n =30) and physical saline group ( n =15). The other 15 rabbits were in shaned injection group. The animals were killed on day4, day7 and day10 to observe the morphologic changes and measure the activity of PKC and NF-κB in basilar artery with immunohistochemisty, substrate phosphorolysis kinase assay, western blot and EMSA. Results The degree of narrow and inflammation reaction in the arterial wall was more significant in animals of simple injecting blood group than those of shamed injection group, in which most significant changes was shown on day 7, and the activity of PKC and NF-κB expression significantly increased on the same period indicating significant positive correlation. PKC inhibitor prominently reduced the degree of narrow and inflammation reaction, and also displayed down-regulation of the expression of the PKC and NF-κB activity with a dose-dependent manner. Conclusions PKC inhibitor significantly reduce the degree of narrow and inflammation reaction in experimental cerebral-vasospasm by inhibit the activity both of PKC and NF-κB expression.
出处
《中华神经外科杂志》
CSCD
北大核心
2003年第3期196-200,共5页
Chinese Journal of Neurosurgery
