脑缺血后碱性成纤维细胞生长因子、表皮生长因子对内源性神经干细胞增殖的影响

目的 观察人脑梗死后室管膜下区(SVZ)及海马齿状回颗粒层(SGZ)区域碱性成纤维细胞生长因子(bFGF)、表皮生长因子(EGF)的表达规律,并探讨其对内源性神经干细胞增殖的影响.方法 (1)选取因脑梗死而死亡的尸检脑标本22例,并按缺血时间(发病至死亡的时间)分为5组,选取因其他疾病死亡(无脑缺血)的尸检脑标本5例为对照组.(2)采用HE染色、免疫组织化学技术观察不同时间点梗死侧侧脑室SVZ区和SGZ区nestin、bFGF、EGF在不同时间点的表达和变化规律.结果 应用SPSS 13.0软件进行统计学分析.结果 (1)与对照组相比,梗死侧SVZ区nestin阳性细胞在24～70 h组开始增加(144±6)个/高倍视野],SGZ区在4.5～10 h组开始增加(11±5)个/高倍视野],120-144 h组达到高峰,SVZ区(38±7)个/高倍视野],SGZ区(54±17)个/高倍视野].216～336 h组逐渐减弱,与对照组比,差异均有统计学意义(均P<0.05).(2)梗死侧bFGF阳性细胞在4.5-10 h组开始增加,SVZ区(8.1±2.9)个/高倍视野],SGZ区(19.0±8.2)个/高倍视野],24～70 h组达到高峰SVZ区(15.6±3.5)个/高倍视野],SGZ区(32.0±5.7)个/高倍视野],72～96 h组开始下降.但仍高于对照组(P<0.05).(3)梗死侧EGF阳性细胞在4.5～10 h组开始增加,SVZ区(4.3±1.6)/高倍视野],SGZ区(7.0±3.7)个/高倍视野],120～144 h组达到高峰SVZ区(27.0±1.4)个/高倍视野],SGZ区(51.5±4.9)个/高倍视野],216～336 h组开始下降,但仍高于对照组(P<0.05).结论 (1)脑缺血后bFGF、EGF表达上调,这可能是脑组织神经元损伤后的一种内源性修复反应.(2)bFGF、EGF可以激活来自于中枢神经系统不同区域的神经元前体细胞潜在的再生能力,促进内源性神经干细胞增殖.

Influences of bFGF and EGF on the proliferation and differentiation of endogenous neural stem cells after cerebral infarction in human

Objective To investigate the relationship of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) and proliferation of endogenous neural stem cells (NSCs) after human cerebral infarction.Methods Paraffin-embedded brain tissues of 22 human fatal cases of CI from the brain tissues around subventricular zone and subgranular layer zone were stained with HE and immunohistochemistry stain.The endogenous neural stem cells were marked by nestin.The expression changes of EGF,bFGF and nestin in the perihematomal tissues were analysised with the SPSS 13.0 system.Results(1) Compared with the controls,the number of nestin-positive cells increased at 24 - 72 h (14±6)/HP in the ipsilateral SVZ and began to rise at 4.5 -10 h (11 ±5)/HP in the ipsilateral SGZ, reached maximum at 120 - 144 h(( 38 ± 7 )/HP in the SVZ,(54 ± 17 )/HP in the SGZ, and decreased markedly at 216 -336 h,but it was still elevated compared with the controls (P <0.05).(2) The number of bFGF-positive cells increased at 4.5 - 10 h (8.1±2.9)/HP in the SVZ,(19.0± 8.2)/HP in the SGZ, reached maximum at 24 -70 h(15.6 ±3.5)/HP in the SVZ, (32.0 ±5.7)/HP in the SGZ and decreased at 72 - 96 h, but it was still elevated compared with the controls(P < 0.05 ).③ The number of EGF- positive cells increased at 4.5 - 10 h (4.3 ± 1.6 )/HP in the SVZ,(7.0 ± 3.7 )/HP in the SGZ, reached maximum at 120 - 144 h (27.0 ± 1.4)/HP in the SVZ, (51.5 ± 4.9)/HP in the SGZ and decreased at 216 -336 h, but it was still elevated compared with the controls (P <0.05).Conclusions Perhaps the increased expression of EGF and bFGF after CI was a reaction of endogenous reparation and it correlated with the proliferation and endogenous of neural stem cells in human.