丁基苯酞通过激活PI3K/Akt/GSK-3β信号通路及其在局部脑缺血损伤脑梗死中的神经保护作用  

Regulation mechanisim of butylphthalide in PI3K/Akt/GSK-3 signaling pathway and its neuroprotective effect on cerebral infarction after local cerebral ischemia

作　　者：王晓荣 乌云高娃[2] 赵福全[1] 高玉峰[1] WANG Xiaorong;WU Yungaowa;ZHAO Fuquan;GAO Yufeng(Department of Mongolian Medicine Cerebrovascular Intervention,Affiliated Hospital of Inner Mongo lia University for the Nationalities,Tongliao 028000,China)

机构地区：[1]内蒙古民族大学附属医院蒙医脑血管介入科,内蒙古通辽028000 [2]内蒙古民族大学附属医院蒙西医肾病科,内蒙古通辽028000

出　　处：《实用医学杂志》2019年第19期2998-3003,共6页The Journal of Practical Medicine

基　　金：内蒙古民族大学自然科学研究项目（编号：NMDYB18090）

摘　　要：目的探讨丁基苯酞(butylphthalide,NBP)对局部脑缺血损伤脑梗死的保护作用及在PI3K/Akt/GSK 3β信号通路的调节机制。方法将100只12~15周龄的SPF级Wistar雄性大鼠随机分为5组(n=20):假手术组(Sham组)、模型组(Model组)、丁基苯酞组(NBP组)、P13K特异性抑制剂LY294002组(LY组)和丁基苯酞+LY294002组(NBP+LY组),采用大脑中动脉阻塞法构建大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)模型,造模后第1天开始,NBP组、LY组、NBP+LY组分别腹腔注射10 mg/kg NBP、10 mg/kg LY和10 mg/kg NBP+10 mg/kg LY,注射剂量10μL,每天1次,连续给药7 d,Sham和Model组腹腔给予等量生理盐水。第7天给药30 min后对大鼠进行神经功能缺损程度(mNNS)评分,并采用磁共振成像法测量脑梗死体积,再用尼氏染色检测脑组织中神经元数损伤情况,同时在光镜下观察记录完整神经元数目,蛋白免疫印迹检测PI3K/Akt/GSK 3β信号通路中的Akt、P Akt、GSK 3β、P GSK 3β蛋白表达。结果与Sham组相比,Model组大鼠神经功能损伤评分明显升高,脑梗死体积明显增大,脑组织中完整的神经元数量及Akt、GSK 3β磷酸化水平明显下降,差异有统计学意义(P<0.05);与Model组相比,NBP组神经功能损伤评分明显下降,脑梗死体积明显减小,脑组织中完整神经元的数量及Akt、GSK 3β磷酸化明显升高,差异有统计学意义(P<0.05);LY组、NBP+LY组与Model组各指标相比组间差异无统计学意义(P>0.05)。结论NBP可以激活缺血性脑梗死所致的PI3K/Akt/GSK 3β信号通路,从而减轻神经功能损害,发挥对局部缺血致脑梗死的保护作用。Objective To investigate the protective effect of butylphthalide(NBP)on cerebral infarction after focal cerebral ischemia and its regulation mechanism in PI3K/Akt/GSK 3βsignaling pathway.Methods To tally 100 SPF Wistar male rats aged 12~15 weeks were randomly divided into sham group,model group,NBP group,P13K specific inhibitor LY294002 group(LY group)and NBP+LY group,with 20 rats in each group.Mid dle cerebral artery occlusion(MCAO)model was established.From the 1st day after molding,NBP group,LY group and NBP+LY group were intraperitoneally injected with 10 mg/kg NBP,10 mg/kg LY and 10 mg/kg NBP+10 mg/kg LY,respectively.The injection dose was 10μL once a day for 7 consecutive days,and the sham and model group were given the same amount of normal saline in the abdominal cavity.Thirty minutes after the adminis tration on the 7th day,rats were scored for neurological deficit degree(mNNS).The volume of cerebral infarction was measured by magnetic resonance imaging(MRI).Then the number of neurons in brain tissue was measured by Nissl staining.At the same time,the number of complete neurons was observed and recorded under light micro scope.PI3K/Akt/GSK 3βsignal was detected by Western blotting.The expression of Akt,P Akt,GSK 3βand P GSK 3βproteins in the pathway were detected.Results Compared with those in sham group,neurological impair ment score in model group was significantly increased;the volume of cerebral infarction was significantly in creased;the number of intact neurons,Akt,and GSK 3βphosphorylation levels in brain tissue decreased signifi cantly,and the difference was statistically significant(P<0.05).Compared with those in model group,neurologi cal impairment score in NBP group was significantly decreased;the volume of cerebral infarction was significantly reduced;the number of intact neurons,Akt,and GSK 3βphosphorylation in brain tissue significantly increased,and the difference was statistically significant(P<0.05).There was no significant difference between LY group and NBP+LY group and model gr

关 键 词：丁基苯酞 1-磷脂酰肌醇3-激酶 蛋白质丝氨酸苏氨酸激酶 糖原合成酶激酶3 细胞凋亡 缺血性脑损伤 大鼠 

分 类 号：R74[医药卫生—神经病学与精神病学]