CAJ | 학술논문

目的：探讨Wnt／β-连环蛋白（β-catenin ）通路对大鼠脑出血的保护作用机制。方法：96只成年SD雄性大鼠随机分为假手术组、脑出血组、脑出血假干预组、siDkk-1干预组4组，采用Real-time PCR方法检测各组大鼠脑出血后24、72 h脑组织中Wnt-1和糖原合成酶激酶3β（ GSK-3β） mRNA表达的变化，采用Western blot法检测各组大鼠脑出血后24、72 h脑组织中β-catenin表达的变化，各组大鼠处死前均进行行为学检测。结果：大鼠脑出血后24和72 h，Wnt-1 mRNA水平与假手术组相比均降低，经siDkk-1干预后，Wnt-1 mRNA水平较脑出血假干预组升高（F＝9．040和26．400， P均＜0．05）。大鼠脑出血后24和72 h，GSK-3βmRNA 水平与假手术组相比均升高，经siDkk-1干预后，GSK-3βmRNA水平较脑出血假干预组下降（F＝41．100和17．800， P均＜0．001）。大鼠脑出血后24和72 h，β-catenin蛋白的表达较假手术组均升高，经siDkk-1干预后，其表达较脑出血假干预组进一步升高（ F＝15．100和14．000， P均＜0．05）。大鼠脑出血后24和72 h，刺激触须前肢上抬比例较假手术组降低，经siDkk-1干预后，前肢上抬比例较脑出血假干预组升高（F＝2450．000和2230．000，P均＜0．001）。结论：Wnt／β-catenin通路对脑出血大鼠有保护作用，可能是通过活化Wnt-1、抑制GSK-3β，进而导致β-catenin 在胞浆中聚集、移位入核后启动Wnt下游靶基因的转录所致。
목적：탐토Wnt／β-련배단백（β-catenin ）통로대대서뇌출혈적보호작용궤제。방법：96지성년SD웅성대서수궤분위가수술조、뇌출혈조、뇌출혈가간예조、siDkk-1간예조4조，채용Real-time PCR방법검측각조대서뇌출혈후24、72 h뇌조직중Wnt-1화당원합성매격매3β（ GSK-3β） mRNA표체적변화，채용Western blot법검측각조대서뇌출혈후24、72 h뇌조직중β-catenin표체적변화，각조대서처사전균진행행위학검측。결과：대서뇌출혈후24화72 h，Wnt-1 mRNA수평여가수술조상비균강저，경siDkk-1간예후，Wnt-1 mRNA수평교뇌출혈가간예조승고（F＝9．040화26．400， P균＜0．05）。대서뇌출혈후24화72 h，GSK-3βmRNA 수평여가수술조상비균승고，경siDkk-1간예후，GSK-3βmRNA수평교뇌출혈가간예조하강（F＝41．100화17．800， P균＜0．001）。대서뇌출혈후24화72 h，β-catenin단백적표체교가수술조균승고，경siDkk-1간예후，기표체교뇌출혈가간예조진일보승고（ F＝15．100화14．000， P균＜0．05）。대서뇌출혈후24화72 h，자격촉수전지상태비례교가수술조강저，경siDkk-1간예후，전지상태비례교뇌출혈가간예조승고（F＝2450．000화2230．000，P균＜0．001）。결론：Wnt／β-catenin통로대뇌출혈대서유보호작용，가능시통과활화Wnt-1、억제GSK-3β，진이도치β-catenin 재포장중취집、이위입핵후계동Wnt하유파기인적전록소치。
Aim:To investigate the neuroprotective effect of Wnt/β-catenin signaling pathway on intracranial hemor-rhage(ICH) in rats.Methods:A total of 96 adult SD rats were allocated into sham-operation group,ICH group,ICH+ve-hicle-treated group,and ICH+siDkk-1 group.The mRNA expressions of Wnt-1 and GSK-3βwere assessed by Real-time PCR at 24 and 72 h after ICH respectively .The expression of β-catenin was evaluated by Western blot analysis .Behavioral test was performed by the vibrissae-elicited forelimb-placing test in different groups .Results:There were remarkably down-regulated expression of Wnt-1 mRNA following ICH at 24 and 72 h, and the mRNA level of Wnt-1 was elevated after siDkk-1 administration(F=9.040 and 26.400, P<0.05).Increased GSK-3βmRNA expression was observed at 24 and 72 h af-ter ICH, and the mRNA level of GSK-3βwere reversed after siDkk-1 administration ( F =41.100 and 17.800, P <0.001).Western blot analysis showed that β-catenin protein was increased at 24 h and 72 h after ICH respectively, and the level of β-catenin was further up-regulated after being treated by siDkk-1 compared with ICH +vehicle-treated group (F=15.100 and 14.000, P<0.05).Meanwhile, decreased behavior scores regarding forelimb use asymmetry was found in the ICH group .However , the behavior scores regarding forelimb use asymmetry was improved after siDkk-1 administra-tion than those in the ICH+vehicle-treated group at 24 and 72 h after ICH(F=2 450.000 and 2 230.000, P<0.001). Conclusion:Wnt/β-catenin signaling pathway has neuroprotective effects against secondary brain injury following ICH , which may be associated with activation of Wnt-1, inhibition of GSK-3βresulting in β-catenin aggregation in the cyto-plasm,subsequent nuclear translocation and the downstream neuroprotective gene transcription .