Src激酶抑制剂PP2对癫痫持续状态性大鼠脑水肿形成及ERK1/2和P38信号通路的影响  

Effects of Src kinase inhibitor PP2 on brain edema formation and ERK1/2 and P38 signaling pathways in epileptic persistent state rats

作　　者：杨子茵 李宁 黄军 李佳宇 高安亮 YANG Ziyin;LI Ning;HUANG Jun;LI Jiayu;GAO Anliang(Department of Neurosurgery,Second Affiliated Hospital of Chengdu Medical College,China National Nuclear Corporation 416 Hospital,Chengdu 610051,China)

机构地区：[1]成都医学院第二附属医院核工业四一六医院神经外科,成都610051

出　　处：《山西医科大学学报》2021年第2期173-178,共6页Journal of Shanxi Medical University

基　　金：四川省卫生和计划生育委员会科研课题(普及应用项目)(17pj189)。

摘　　要：目的探讨Src激酶抑制剂PP2对癫痫持续状态性大鼠脑水肿形成及ERK1/2和P38信号通路的影响。方法60只大鼠建立癫痫模型,随机分为:模型组、PP2低剂量(1 nmol)组、PP2中剂量(2.5 nmol)组、PP2高剂量(5 nmol)组、丙戊酸钠(5 mg/kg)组,每组12只;另取12只SD大鼠作为对照组。分组处理后,以脑电图仪检测记录各组大鼠脑电波(EEG);观察记录癫痫发作次数、持续时间;计算脑组织含水量检测各组大鼠脑水肿情况;HE染色检测各组大鼠皮质神经元病理变化;免疫印记法检测各组大鼠脑组织ERK1/2和P38通路相关蛋白p-ERK1/2、ERK1/2、p-P38、P38表达。结果对照组大鼠皮层区脑电波正常,大脑皮质神经元无病理改变。模型组大鼠皮层区出现散在性痫波,多为尖波、棘波、棘慢复合波,并大量痫性放电,脑电波发生异常改变;皮质神经元细胞形态不规则,变小皱缩,排列紊乱,细胞较多凋亡,数量减少,出现病理损伤。PP2低、中、高剂量组、丙戊酸钠组大鼠脑电波异常改变及皮质神经元细胞病理损伤均减轻,且减轻程度随剂量升高呈依赖性增强,PP2高剂量组与丙戊酸钠组大鼠改变及损伤减轻程度相似。与对照组相比,模型组大鼠癫痫发作次数及持续时间、脑组织含水量、脑皮层区p-ERK1/2/ERK1/2、p-P38/P38显著升高(P<0.05);与模型组相比,PP2低、中、高剂量组和丙戊酸钠组大鼠癫痫发作次数及持续时间、脑组织含水量、脑皮层区p-ERK1/2/ERK1/2、p-P38/P38降低(P<0.05),且PP2三组之间呈剂量依赖性,PP2高剂量组与丙戊酸钠组相比,上述各指标差异无统计学意义(P>0.05)。结论Src激酶抑制剂PP2可减轻脑水肿,缓解癫痫发作,保护神经功能,改善其临床症状,可能通过抑制ERK1/2和P38信号激活实现。Objective To investigate the effects of PP2,a Src kinase inhibitor,on the formation of brain edema and ERK1/2 and P38 signaling pathways in epileptic persistent state rats.Methods Epileptic rat model was established in 60 rats,and they were randomly divided into model group,low-dose PP2(1 nmol)group,middle-dose PP2(2.5 nmol)group,high-dose PP2(5 nmol)group and so-dium valproate(5 mg/kg)group,with 12 rats in each group.Another 12 SD rats were used as control group.After treatment,the electroencephalogram of rats in each group was detected and recorded by electroencephalograph,the frequency and duration of epileptic seizures in each group were observed and recorded,the brain water content was calculated and the brain edema of rats in each group was detected,the pathological changes of cortical neurons were detected by HE staining,the expression of ERK1/2 and P38 pathway-related proteins p-ERK1/2,ERK1/2,p-P38,P38 in the brain tissues of rats in each group was detected by Western blot.Results In control group,the electroencephalogram in the cortex was normal,and the cortical neurons had no pathological changes.In model group,there were sporadic epilepsy waves in the cortical area,mostly sharp waves,spike waves and slow spines,a large number of epilepsy discharges and abnormal changes of brain waves were observed,and the cortical neuronal cells were irregular in shape,shrunk,disordered in arrangement,with more apoptotic,decreased number and pathological damage.In low-,medium-,high-dose PP2 groups and sodium valproate group,the abnormal changes of EEG and pathological damage of cortical neurons were alleviated,and the degree of reduction was enhanced in a dose-dependent manner with the increase of PP2.The changes and injury reduction were similar in high-dose PP2 group and sodium valproate group.Compared with control group,the frequency and duration of seizures,the water content of brain tissue,p-ERK1/2/ERK1/2 and p-P38/P38 in the cerebral cortex were significantly increased in model group(P<0.05).Compared with model g

关 键 词：Src激酶抑制剂PP2 癫痫 ERK1/2 P38 脑水肿 

分 类 号：R742.1[医药卫生—神经病学与精神病学]