MAPKs阻滞剂U0126对创伤性脑损伤大鼠学习记忆功能的影响及机制探讨  

Protective effects of MAPKs inhibitor U0126 on learning and memory function of rats with traumatic brain injury

作　　者：刘兴宇[1] 甄艳凤[1] 崔建忠[1] 高俊玲 

机构地区：[1]唐山市工人医院,河北唐山063000 [2]华北理工大学基础医学院

出　　处：《山东医药》2016年第18期21-24,共4页Shandong Medical Journal

基　　金：河北省自然科学基金资助项目(H2012401071);河北省引进留学人员资助项目(2012-02)

摘　　要：目的观察丝裂原活化蛋白激酶(MAPKs)阻滞剂U0126对创伤性脑损伤(TBI)大鼠学习记忆功能的影响,并探讨其机制。方法将313只成年雄性SD大鼠随机分为假手术组52只、模型组87只、DMSO组87只、U0126组87只,除假手术组外其余各组制备大鼠弥漫性脑创伤模型。U0126组将0.1 mg/kg U0126以0.1 mmol/L的PBS稀释至300μL,于造模前30 min尾静脉注射。DMSO组同时点尾静脉注射相同含量DMSO稀释溶液,假手术组和模型组同时点尾静脉注射生理盐水300μL。造模30 min、3 h、12 h、24 h、48 h、72 h、7 d取各组大鼠各5只(假手术组3只),采用TUNEL法观察各组海马组织神经细胞凋亡情况。造模30 min、3 h、12 h、24 h、48 h、72 h、7 d取各组大鼠各6只(假手术组3只),采用Western blot法检测各组海马组织磷酸化细胞外信号调节激酶1/2(p-ERK1/2)蛋白表达。造模14、16、18、21 d取各组大鼠各10只,采用Morris水迷宫实验观察大鼠空间学习记忆能力。结果造模48、72 h时,U0126组海马组织神经细胞凋亡数少于DMSO组、模型组,P均<0.05;造模24、48、72 h时,U0126组、DMSO组、模型组海马组织神经细胞凋亡数均多于假手术组,P均<0.05;造模48、72 h时,U0126组海马组织p-ERK1/2蛋白相对表达量低于模型组、DMSO组,P均<0.05;造模12、24、48、72 h时,U0126组、DMSO组、模型组海马组织p-ERK1/2蛋白相对表达量均短于假手术组,P均<0.05;造模16、18、21 d时U0126组大鼠潜伏期均短于DMSO组、模型组,P均<0.05;造模14、16、18、21 d时U0126组、DMSO组、模型组大鼠潜伏期均长于假手术组,P均<0.05。相关性分析结果显示,海马区神经细胞凋亡数与p-ERK1/2表达呈正相关(r=0.468,P=0.002)。结论 U0126可抑制TBI大鼠海马神经细胞凋亡,提高大鼠的学习记忆能力,可能与降低海马组织中pERK1/2表达有关。Objective To observe the protection of mitogen-activated protein kinase （MAPK） inhibitor U0126 on learning and memory function of rats with traumatic brain injury （TBI） and to investigate its mechanism. Methods Male Sprague-Dawley rats （ n = 313 ） were randomly divided into four groups ： the sham operation group （ n = 52）, TBI group （ n = 87）, DMSO group （n = 87） and U0126 group （n = 87）. Except the TBI group, diffused brain injury rat models were established in the other groups. In the U0126 group, 0.1 mg/kg U0126 was dissolved in PBS, and 0.1 mM PBS was dilu- ted to the total amount of 3.00 μL, then, this solution was injected into the rats 30 min before modeling by caudal vein. Rats in the DMSO group were injected with the same amount of DMSO dilute solution, and rats in the sham operation group and TBI group were injected with 300 μL normal saline. The in situ apoptosis assay was used to observe the nerve apoptosis of hippocampus of each group at 30 min, 3 h, 12 h, 24 h, 48 h, 72 h and 7 d after modeling （n =5 respectively, except for sham operation group n =3）. The phosphorylated extracellular signal-regulated kinase （ERK） 1/2 （p-ERK1/2） pro- tein was detected in each group by Western blotting at 30 min, 3 h, 12 h, 24 h, 48 h, 72 h and 7 d after modeling （n = 6 respectively, except for sham operation group n = 3）. The learning and memory function was evaluated by Morris watermaze on the 14th, 16th, 18th and 21rd day after modeling in each group （each n = 10）. Results The number of nerve cell apoptosis of hippocampus in the U0126 group was lower than that of DMSO and TBI groups at 48 h and 72 h after mod- eling, all P 〈 0.05 ; the number of nerve cell apoptosis of hippocampus in the U0126, DMSO and TBI groups was all higher than that of the sham operation group at 24 h, 48 h and 72 h, all P 〈0.05 ; the relative expression of p-ERK1/2 in hippo- campus of the U0126 group was lower than that of the DMSOand TBL groups at 48 h and 72 h after modehng, all P �

关 键 词：创伤性脑损伤 学习记忆功能 丝裂原活化蛋白激酶阻滞剂 磷酸化细胞外信号调节激酶1/2 

分 类 号：R651.1[医药卫生—外科学]