摘要
目的 研究外源性碱性成纤维细胞生长因子 (bFGF)缩小局灶性脑缺血梗死灶的机制。 方法 用免疫组化ABC法检测在局灶性脑缺血模型上给予生理盐水或bFGF后早期生长反应蛋白 1(Egr 1) ,bFGF ,碱性成纤维细胞生长因子受体 (bFGFR)的动态表达。结果 给药组在 3h～ 3d各时间段梗死灶均有不同程度的缩小。对照组和给药组Egr 1表达均表现为 3～ 6h的增强过程 ,但给药组更强于对照组。对照组 12h见有bFGF表达增强 ,而bFGFR表达 3h到达高峰 ,6h起下降 ,12h时bFGFR的表达已恢复至正常水平 (出现了配体和受体表达时相上不匹配 )。给药组bFGF表达提前且增强 ,3h即见有bFGF表达增强 ,6h时出现第一峰 ,从而与bFGFR 3～ 6h的表达增强过程相吻合。 结论 外源性bFGF能缩小梗死灶 ,该神经保护作用是通过Egr 1蛋白高表达使内源性bFGF的表达增高且提前 。
Objective To explore the protective mechanism of exogenous basic fibroblast growth factor (bFGF) against focal brain ischemia. Methods Wistar rats received bFGF or saline after 2 h of middle cerebral artery occlusion (MCAO) and sacrificed at designed time intervals as 3,6,12 h, 1,3,7,14 d after the administration. The infarct area was observed by H&E staining and detected by morphometry. The expression of early growth factor-1 (Egr-1),bFGF, bFGF receptor (bFGFR) was determined by immunohistochemistry (ABC method). Results The infarct area of bFGF administration group reduced 17%-24%. Enhanced expression of Egr-1 was observed both in neurons and astrocytes at 3-6 h after administration of saline, but it was stronger in bFGF group. It implied that exogenous bFGF might affect the expression of endogenous bFGF through changing the expression of Egr-1 protein. bFGF immnuoreactivity showed first peak at 6 h in bFGF group, which indicated exogenous bFGF could induce the expression of endogenous bFGF both in astrocytes and also in neurons, but the intensity of immunostain in neurons was much weaker than that in astrocytes. In saline group mainly in astrocytes and neurons, bFGFR presented an early, transient expression, reached its maximal level at 3 h,declinled at 6 h.The expression of bFGFR was prior to the peak of endogenous bFGF expression. It meant that bFGFR could not be combined with its ligand in saline group, but the enhanced expression of endogenous bFGF induced by exogenous bFGF appeared earlier and overlapped with bFGFR expression. Conclusion The exogenous bFGF may enhance endogenous expression of bFGF through raising Egr-1 expression level, and the expression of endogenous bFGF showed an early increase, which may overlap with bFGFR expression. It might be the protective mechanism of exogenous bFGF against focal brain ischemia.
基金
国家自然科学基金(39870254)
