幼龄和老龄大鼠液压颅脑伤后NGFmRNA表达差异

Expression differences of nerve growth factor mRNA in young and aged rats following fluid-percussion brain injury

目的 观察幼龄和老龄大鼠颅脑损伤后神经生长因子信使RNA(nervegrowthfactormRNA ,NGFmRNA)表达差异 ,探讨老年动物中枢神经损伤后神经功能缺失较多的病理生理机制 ,以及改善老年颅脑损伤预后的方法。方法 采用大鼠侧方液压打击颅脑损伤模型 ,应用原位杂交方法和计算机显微图象分析技术 ,比较幼龄 (2～ 3个月 )和老龄 (15个月 )大鼠脑损伤后 12h脑内NGFmRNA表达水平的差异 ,并用β2 受体激动剂克仑特罗 (clenbuterol,CLE)作为干预手段 ,观察其对幼龄和老龄大鼠受损脑组织NGFmRNA表达的调节作用。结果 液压打击伤后 12h ,两组大鼠损伤脑组织NGFmRNA表达均有不同程度的增加 ,但是老龄鼠损伤侧大脑皮层NGFmRNA表达明显低于幼龄鼠 (P <0 .0 5 ) ;伤后立即应用CLE(0 .5mg/kg ,腹腔注射 )并不提高幼龄大鼠受伤脑组织NGFmRNA的表达 ,但可显著提高老龄鼠NGFmRNA的表达 (P <0 .0 1)。结论 脑损伤早期老龄鼠NGFmRNA表达较低提示老年动物受损脑组织修复能力减低 ,这为我们认识临床上老年颅脑损伤后神经功能缺失较多的原因提供了帮助 ;

Objective To investigate whether there were some differences in the expression of NGFmRNA between the young and aged rats following traumatic brain injury(TBI), and whether the expression of NGFmRNA could be altered by β 2 adrenocepter agonist clenbuterol(CLE).Methods Aged(15 months) and young(2～3 months) Sprague Dawley(SD)rats were subjected to TBI by using lateral fluid percussion brain injury model. Clenbuterol (0.5 mg/kg,intraperitoneally) was administered immediately after fluid percussion injury. The expression of NGFmRNA was analyzed by in situ hybridization and computer imaging analysis.Results In the ipsilateral cerebral cortex and hippocampus, the expression of NGFmRNA increased 12 h after fluid percussion brain injury both in young and aged rats. However, the level of NGFmRNA in the aged rats' cerebral cortex was lower than that in the young rats ( P <0.05). Clenbuterol failed to change NGFmRNA level in young rats, while increased NGFmRNA level in the ipsilateral cerebral cortex of aged rats significantly ( P <0.01).Conclusion The lower expression of NGFmRNA after TBI in the aged rats suggests that the aged mammals present the lower ability in the neurological recovery,and this maybe elucidate the pathophysiological reason that the elderly patients present the higher neurological deficits. Clenbuterol could raise the recovery ability of the aged rats by the up regulation of NGFmRNA expression, thus the clenbuterol may have a potential as therapeutic agent for the treatment of TBI, especially for the aged patients.