CAJ | 학술논문

目的：探讨JAK2／STAT3信号转导通路在大鼠缺血性脑损伤中的作用。方法将54只SD大鼠随机分为假手术组、缺血再灌注组（ I／R组）和JAK2／STAT3通路抑制剂组（ AG组），每组18只。采用改良线栓法制备大鼠大脑中动脉脑缺血再灌注模型。 AG组于再灌注前5 min给予AG4901 mg／kg。制模成功后对大鼠进行神经功能缺损评分，采用TTC染色测脑梗死体积，原位缺口末端标记法测定脑细胞凋亡的变化，免疫组化和Western blot检测缺血周边区脑组织caspase－3及磷酸化STAT3（ p－STAT3）表达。结果与I／R组比较，AG组神经功能缺损评分、脑梗死体积及凋亡细胞数显著降低（均P＜0．05）。与I／R组比较，假手术组、AG组caspase－3免疫阳性细胞及p－STAT3蛋白表达均显著减少（均P＜0．05）。假手术组caspase－3免疫阳性细胞显著少于AG组（ P＜0．05）。结论 JAK2／STAT3信号通路参与了大鼠脑缺血再灌注的损伤，抑制JAK2／STAT3信号通路可以减轻 caspase－3的表达和缺血灌注损伤后神经细胞凋亡，改善神经功能缺损症状。
목적：탐토JAK2／STAT3신호전도통로재대서결혈성뇌손상중적작용。방법장54지SD대서수궤분위가수술조、결혈재관주조（ I／R조）화JAK2／STAT3통로억제제조（ AG조），매조18지。채용개량선전법제비대서대뇌중동맥뇌결혈재관주모형。 AG조우재관주전5 min급여AG4901 mg／kg。제모성공후대대서진행신경공능결손평분，채용TTC염색측뇌경사체적，원위결구말단표기법측정뇌세포조망적변화，면역조화화Western blot검측결혈주변구뇌조직caspase－3급린산화STAT3（ p－STAT3）표체。결과여I／R조비교，AG조신경공능결손평분、뇌경사체적급조망세포수현저강저（균P＜0．05）。여I／R조비교，가수술조、AG조caspase－3면역양성세포급p－STAT3단백표체균현저감소（균P＜0．05）。가수술조caspase－3면역양성세포현저소우AG조（ P＜0．05）。결론 JAK2／STAT3신호통로삼여료대서뇌결혈재관주적손상，억제JAK2／STAT3신호통로가이감경 caspase－3적표체화결혈관주손상후신경세포조망，개선신경공능결손증상。
Objective To investigate the effect of JAK2/STAT3 signaling pathway in rat with cerebral ischemia-reperfusion injury.Methods Fifty-four SD rats were randomly divided into sham group, ischemia-reperfusion ( I/R) group and JAK2/STAT3 pathway inhibitor group (AG group), and there were 18 rats in each group.The middle cerebral artery cerebral ischemia/reperfusion model was builded by modified thread embolism method.AG490 ( 1 mg/kg) were given to the rat of AG group at 5 min before reperfusion.Neurological deficit score was assessed after model building.The infarct volume was measured by TTC staining.The changes of brain cell apoptosis was measured by terminal-deoxynucleoitidyl transferase mediated nick end labeling.The expression of caspase-3 and phosphorylated STAT3 ( p-STAT3) were detected by immunohistochemistry and Western blot respectively.Results Compared with those in I/R group, the neurological deficit score, infarct volume and apoptotic cell number in AG group were significantly decreased ( all P<0.05 ) .Compared with those in I/R group, the positive cell of caspase-3 and p-STAT3 expression in sham group and AG group were significantly decreased ( all P<0.05 ) .The positive cell of caspase-3 in sham group was significantly decreased than that in AG group ( P<0.05 ) .Conclusion JAK2/STAT3 signaling pathway is involved in the rat with cerebral ischemia-reperfusion injury, inhibiting JAK2/STAT3 signaling pathway can reduce the expression of caspase-3 and neuronal apoptosis after ischemia-reperfusion injury, and it can improve neurological deficit symptoms.