摘要
目的观察脑室注射神经生长因子(NGF)对脑缺血再灌注大鼠神经再生的影响及其与环磷酸腺苷-蛋白激酶A(cAMP-PKA)信号途径的关系。方法采用线栓法制作大鼠脑缺血再灌注模型,将60只大鼠分为假手术组(对照组),单纯脑缺血再灌注组(缺血组),NGF1组,NGF2组(脑缺血再灌注并脑室注射NGF,分别注入0.5及2.5μg/100 g体重)。用放免法检测缺血周边区脑组织cAMP的含量,逆转录聚合酶链反应的方法检测生长相关蛋白43(GAP-43)及蛋白激酶A(PKA)mRNA的表达。结果缺血组6、24 h cAMP的含量下降,GAP-43及PKA mRNA表达减少,NGF治疗组脑组织GAP-43 mRNA表达较缺血组增加,且这种变化与cAMP的含量及PKA mRNA表达增加相一致,并呈剂量依赖性。结论NGF能够促进脑缺血再灌注后的轴突再生,cAMP-PKA信号途径在这个过程中起重要作用。
Objective To investigate the effect of intra-cerebroventricular administration of NGF (nerve growth factor) on axon regeneration and cAMP-PKA signal pathway in cerebral ischemia-reperfusion rats. Methods The focal cerebral ischemia and reperfusion model was established by nylon monofilament occlusion method in rats. Sixty rats were randomly assigned to sham operated(control)group, cerebral ischemia-reperfusion only group and NGF Ⅰ and NGF Ⅱgroups(intra-cerebroventricular injection of NGF 0.5 μg/100 mg and 2.5 μg/ 100 mg respectively). The contents of cAMP in cerebral cortex of rats were measured by radioimmunoassay (R/A) and the changes of protein kinase A(PKA) and growth associated protein(GAP)-43 mRNA expression were determined by RT-PCR technique. Results The contents of cAMP and the expression levels of PKA and GAP-43 mRNA decreased at 6 h and 24 h after cerebral ischemia-reperfusion. NGF elevated the expression level of GAP-43 mRNA, increased the contents of cAMP and activated PKA. The change of GAP-43 coincided with increase in cAMP content and PKA mRNA expression. All these changes were dose dependent. Conclusion NGF can improve axon regeneration and the cAMP-PKA signal pathway plays an important role in this process.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2006年第5期350-353,共4页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
湖北省科技攻关项目资助(2003AA301C50)