碱性成纤维细胞生长因子对癫痫大鼠海马神经元凋亡的影晌

The effects of basic fibroblast growth factor on neuronal apoptosis in the hippocampus of epileptic rats

目的探讨碱性成纤维细胞生长因子(bFGF)对致痫大鼠的神经保护作用及可能机制。方法给予戊四氮(PTZ)致痫大鼠每日腹腔注射bFGF(bFGF组,n=36)、生理盐水(NS组,n=36),分别于痫性发作后6h、12h、24h、48h、3d、5d处死取脑,切片进行bcl-2、caspase-3染色,用原位末端标记(TUNEL)方法检测海马神经元凋亡细胞。结果痫性发作6h后两组海马CA1、CA3区的bcl-2、caspase-3、TUNEL染色阳性表达差异无统计学意义(P>0.05);12～48 h表达逐渐增强,bFGF组bcl-2、TUNEL的表达显著高于NS组,bFGF组caspase-3的表达显著低于NS组(P均<0.01);3d后表达减弱.bFGF组与NS组的差异无统计学意义(P>0.05)。结论bFGF能显著减轻癫痫所致的海马神经元凋亡,提示可能通过调控bcl-2和caspase-3基因的表达发挥作用。

Objective To investigate the neuroprotective effects of basic fibroblast growth factor （bFGF） on epileptic rats and the possible mechanisms. Methods Rats with pentylenetetrazol-induced seizures were randomly divided into the bFGF group （intraperitoneally injected with bFGF at the daily frequency） and NS group （control group, intraperitoneally injected with normal saline at the daily frequency）, 36 rats in each group; all the rats were executed at 6 h, 12 h, 24 h, 2 d, 3 d and 5 d after seizures and their heads were removed; the removed brain tissues were then sliced to undergo immunohistochemical staining, which was performed to observe the expressions of bcl-2 and caspase-3, and the terminal deoxynucletidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）, which was used to detect the apoptotic cells ofhippocampal neurons. Results Bcl-2, caspase-3 and TUNEL staining： differences of positive expressions in hippocampal CA1 and CA3 regions 6 h after seizures were not significant between the bFGF and NS groups （P〉0.05）; the positive expressions increased gradually during 12 h and 48 h, when the expressions of bcl-2 and TUNEL-positive cells were significantly higher in the bFGF group than that in the NS group and the caspase-3 expression in the bFGF group was significantly lower than that in the NS group, so the differences had statistical significance （P〈0.01 ,P〈 0.001）; the positive expressions decreased 3 d later after seizures and differences between the bFGF and NS groups had no statistical significance （P 〉0.05）. Conclusion The injection of bFGF can remarkably reduce the hippocampal neuronal apoptosis induced by seizures, indicating that regulating the expressions of bcl-2 and caspase-3 and inhibiting neuronal apoptosis may exert the neuroprotective effects of bFGF.