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目的探讨丰富环境对颞叶癫癇大鼠齿状回新生细胞分化和存活的影响及其相关分子机制。方法成年Wistar大鼠随机分为4组:假手术组、丰富环境+假手术组、癫癇组、丰富环境+癫癇组,各组均n=15。大鼠侧脑室注射海人酸制作颞叶癫癇模型。丰富环境干预30 d后,应用免疫荧光技术观察大鼠海马齿状回的新生细胞分化和存活情况,用Western blot方法检测各组海马脑源性神经营养因子(BDNF)、cAMP应答元件结合蛋白(pCREB)、蛋白激酶A(PKA)表达水平。结果丰富环境+假手术组、丰富环境+癫癇组齿状回新生细胞标记物(Brd U)和新生成熟神经细胞标记物(Brd U/Neu N)阳性细胞数分别多于假手术组、癫癇组(P<0.05),而新生星形胶质细胞Brd U/GFAP阳性细胞数无统计学意义,并且丰富环境+假手术组、丰富环境+癫癇组海马BDNF和pCREB蛋白表达水平分别高于假手术组、癫癇组(P<0.05),而PKA蛋白表达水平无增高。结论丰富环境可能通过增强p CREB/BDNF通路促进成年颞叶癫癇大鼠海马齿状回的神经发生。
Objective To investigate the effects of enriched environment on the differentiation and survival of the dentate gyrus of temporal lobe epilepsy rats and its related molecular mechanisms. Methods Adult Wistar rats were randomly divided into 4 groups: sham operation group, rich environment + sham operation group, epilepsy group, rich environment + epilepsy group, n = 15 in each group. Rat intracerebroventricular injection of kainic acid to make temporal lobe epilepsy model. After 30 days of environmental intervention, immunofluorescence was used to observe the differentiation and survival of neonatal rat hippocampal dentate gyrus. Western blot was used to detect the expression of BDNF, cAMP response element binding protein pCREB), protein kinase A (PKA) expression levels. Results The numbers of BrdU and BrdU / Neu N positive cells in the enriched environment + sham operation group and enriched environment + epilepsy group were more than those in the sham operation group, the epilepsy group (P <0.05), while the number of Brd U / GFAP positive cells in astrocytes was not significantly different between the sham operation group and the sham-operation group and the enriched environment + epilepsy group Group, epilepsy group (P <0.05), while PKA protein expression level was not increased. Conclusion Enriched environment may promote the neurogenesis of hippocampal dentate gyrus in adult temporal lobe epilepsy rats by enhancing p CREB / BDNF pathway.