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

Abstract

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 of ischemic 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. ▪ Focal 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. ▪ The rats in the treatment group were intraperitoneally injected with 10 μ/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. ▪ 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. ▪ Expression 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.