Wnt pathway in the formation of ischemic brain injury Interventional pathway of basic fibroblast growth factor

Xuesong Xing; Weili Lü; Li Guo

摘要：BACKGROUND: Basic fibroblast growth factor (bFGF) can reduce neuronal apoptosis following ischemia/reperfusion (I/R) injury. Mechanism of the phenomenon should be elucidated.OBJECTIVE: The goal of this study was to observe the effect of bFGF on the expressions of Dickkopf-1(DKK-1) and β-catenin in the Wnt pathway in hippocampal tissue of rats following brain I/R injury, in order to investigate the role of Wnt pathway in the formation ofischemic brain injury.DESIGN: Randomized controlled experiment.SETTING: Shenyang Medical College.MATERIALS: Thirty healthy 3 months old male Wistar rats, weighing 300 - 350 g, were provided by the Experimental Animal Center of Shenyang Medical College. Thirty rats were randomized into sham-operation group, model group and treatment group. Goat anti-rat monoclonal antibody β-catenin was purchased from SANTA CRUZ Company. BFGF was developed by Beijing SL Pharmaceutical Co., Ltd.METHODS: This experiment was carried out in the Shenyang Medical College between November 2005 and May 2006. ①Focal brain I/R by suture-occluded method was modeled in rats in the treatment group and model group. Their middle cerebral artery was occluded 1 hour and reperfused for 24 hours. While in the sham-operation group, only the right common carotid artery and external carotid artery of rats were occluded for 90 minutes. ② The rats in the treatment group were intraperitoneally injected with 10 μg/kg bFGF,and those in the other groups were intraperitoneally injected with the same amount of saline.MAIN OUTCOME MEASURES: Following I/R 48 hours, the expressions of β-catenin and Dickkopf-1 mRNA in the neurons of hippocampal CA1 region by immunohistochemical SABC and RT-PCR.RESULTS: Following I/R 48 hours, the expressions of β-catenin and Dickkopf-1 mRNA in the neurons of hippocampal CA1 region was evaluated by means of immunohistochemical SABC and RT-PCR. ① Expression of DKK-1 mRNA in the sham-operation group was at low level, it was significantly higher in the model group compared to the sham-operation group; Expression of DKK-1 mRNA in the treatment group was significantly lower than that in the model group. ②Expression of β-catenin in the cerebral cortex and hippocampal cytoplasm of rats: The mean gray scale of β-catenin of model group was significantly lower than that of sham-operation group (74.27±2.65 vs. 111.36±5.39, P ＜ 0.05); The mean gray scale of β -catenin of treatment group was significantly higher than that of model group (86.18±7.41 vs. 74.27±2.65, P＜0.05).CONCLUSION: bFGF may influence Wnt pathway by participating in the regulation of DKK-1 mRNA and β-catenin expressions, and thereby protect neurons.