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目的 探讨脑内移植脑源性神经营养因子 (BDNF)载体细胞对新生大鼠缺氧缺血性脑损伤后存活、运动机能和行为的影响。方法 7d龄新生大鼠一侧颈总动脉结扎联合低氧吸入法制成缺氧缺血性脑损伤模型。在损伤后即刻 ,于单侧皮层内植入构建的可稳定表达和分泌BDNF的大鼠成肌细胞 ,观察植入 4周后大鼠存活、运动机能和行为的变化。结果 BDNF载体细胞可稳定表达BDNFmRNA ,其分泌上清液可维持PC1 2细胞存活、促进突触生长 ,脑内移植后 42d ,移植组动物死亡率显著降低 (2 8.6 % ,对照值为 57.7% ) ;倾斜临界角度虽仍低于假伤组 ,但显著高于移植不含BDNF载体细胞的对照组 ;开场行为的水平、垂直运动值均显著高于对照组 ,多数时间点上显著低于假伤组。结论 脑内移植可稳定表达和分泌活性BDNF的载体细胞可显著降低新生大鼠缺氧缺血性脑损伤后的死亡率 ,对运动机能和行为的恢复有良好的促进作用。
Objective To investigate the effects of transplanted brain derived neurotrophic factor (BDNF) on the survival, motor function and behavior of neonatal rats after hypoxic-ischemic brain damage. Methods Hypoxic-ischemic brain damage model was induced by ligation of common carotid artery on the 7th-day old neonatal rats and hypoxia inhalation. Immediately after injury, the constructed rat myoblasts stably expressing and secreting BDNF were implanted into the unilateral cortex to observe the changes of survival, motor function and behavior of rats after 4 weeks of implantation. Results The BDNF vector could stably express BDNF mRNA. The secreted supernatant could maintain the survival of PC12 cells and promote the synapse growth. At 42 days after transplantation, the death rate of BDNF was significantly decreased (22.6% vs 57.7%) . Although the critical angle of tilt was still lower than that of the sham injury group, it was significantly higher than that of the control group without BDNF carrier cells. The level of opening behavior and vertical movement were significantly higher than those of the control group, and were significantly lower than those of the control group group. Conclusions The intracerebral transplantation of stable and expressive BDNF-expressing vector can significantly reduce the mortality of neonatal rats after hypoxic-ischemic brain injury and promote the recovery of motor function and behavior.