CAJ | 학술논문

目的研究联用Janus激酶信号转导及转录激活因子(JAK-STAT)信号通路抑制剂AG490和自由基清除剂二甲基硫脲(DMTU)对大鼠局灶忭脑缺血/再灌注(I/R)损伤的保护作用及其剂蹙-效应关系.方法制备大鼠大脑中动脉阻塞(MCAO)模型.选择雄性SD大鼠.按照随机数字表法分组,每组10只.实验1 设I/R模型组、二甲亚砜(DMSO)对照组、生理盐水(NS)对照组、AG490组、DMTU组以及AG490联合DMTU(A+D)组;实验2分为模型组及高、中、低剂量联合组.于I/R 24、48和72 h对各组人鼠进行神经行为学评分(NBS);72 h后处死动物,测量其脑梗死体积.结果 I/R 24、48和72 h A+D组、AG490组和DMTU组NBS明显高于I/R模型组,脑梗死体积明显小于I/R模型组,其中A+D组脑梗死体积较AG490组和DMTU组明显减小(P均＜0.05).高、中剂链联合组NBS明显高于低剂量联合组和模型组.脑梗死体积明显小于后两组,其中高剂量联合组脑梗死体积较中剂量联合组明显减小(P均＜0.05).而低剂量联合组与模型组之间差异无统计学意义.结论 AG490和DMTU有明显的协同脑保护作用,并呈现剂量依赖性.
목적 연구련용Janus격매신호전도급전록격활인자(JAK-STAT)신호통로억제제AG490화자유기청제제이갑기류뇨(DMTU)대대서국조변뇌결혈/재관주(I/R)손상적보호작용급기제축-효응관계.방법 제비대서대뇌중동맥조새(MCAO)모형.선택웅성SD대서.안조수궤수자표법분조,매조10지.실험1 설I/R모형조、이갑아풍(DMSO)대조조、생리염수(NS)대조조、AG490조、DMTU조이급AG490연합DMTU(A+D)조;실험2분위모형조급고、중、저제량연합조.우I/R 24、48화72 h대각조인서진행신경행위학평분(NBS);72 h후처사동물,측량기뇌경사체적.결과 I/R 24、48화72 h A+D조、AG490조화DMTU조NBS명현고우I/R모형조,뇌경사체적명현소우I/R모형조,기중A+D조뇌경사체적교AG490조화DMTU조명현감소(P균＜0.05).고、중제련연합조NBS명현고우저제량연합조화모형조.뇌경사체적명현소우후량조,기중고제량연합조뇌경사체적교중제량연합조명현감소(P균＜0.05).이저제량연합조여모형조지간차이무통계학의의.결론 AG490화DMTU유명현적협동뇌보호작용,병정현제량의뢰성.
Objective To investigate the neuroprotective effects and dose-response relation by combining JAK-STAT signal pathway inhibitor(AG490)with free radical scavenger dimethylthiourea (DMTU)in rats subjected to focal cerebral ischemia/reperfusion(I/R)injury.Methods In all rats,the middle cerebral artery occlusion(MCAO)was produced by occlusion of right internal carotid artery with a nylon monofilament.One hundred male Sprague-Dawley(SD)rats were divided into ten groups according to random digits table,10 rats were in each group.The first experiment involved I/R modeI controI,dimethyl sulfoxide(DMSO)control,normaI saline(NS)control,AG490,DMTU and combination of AG490 and DMTU(A+D)groups.The second experiment involved model group and three experimental groups in which various doses of DMTU and AG490 were administered.The neurological behavior scores(NBS)were assessed at 24,48 and 72 hours after reperfusion respectively in both experiments,and all the animals were then decapi rated to determine the brain infarct volume after 72 hours.Results The values of NBS in A+D group,AG490 group and DMTU group were higher than those in model group at 24,48 and 72 hours after I/R,and their brain infarct volumes were obviously smaller than model group as well(all P＜0.05).The brain infarct volume in A+D group was obviously smaller compared with AG490 and DMTU alone(all P＜0.05).The values of NBS were higher and the brain infarct volumes were smaller in both high dose and medium dose combination groups than those in low dose combination and model groups respectively(all P＜0.05).In addition,brain infarct volumes in high dose group were smaller than medium dose group(P＜ 0.05),but there was no statistically significant difference between low dose and model groups.Conclusion The combined application of AG490 and DMTU produces a dose-dependent synergistic neuroprotective effect.