TPO对缺氧缺血新生小鼠神经保护作用的实验研究

Experimental Study of Thrombopoietin on Neuroprotective Effect in Neonatal Mice with Hypoxic-Ischemic Brain Damage

目的:研究促血小板生成素(TPO)对缺血缺氧脑损伤(HIBD)新生小鼠神经细胞的保护作用,探讨其机制。方法:将7d龄C57新生小鼠分为假手术对照组(Control)、模型组(HIBD)及TPO保护组(HIBD+TPO),并分别作相应处理。3周后,对比各组小鼠脑组织切片HE染色、神经元特异性烯醇化酶(NSE)原位表达、脑组织冰冻切片细胞内活性氧(ROS)表达以及脑干听觉诱发电位(BAEP)等指标。结果:与对照组相比,HIBD组小鼠脑组织切片病理变化明显,而TPO的运用能够明显减轻这种形态学变化;TPO的治疗减少了由于HIBD带来的NSE细胞外释放,同时也能明显减少神经细胞损伤时细胞内ROS的生成;HIBD组小鼠BAEP各波绝对潜伏期(PL)时长明显大于对照组(P<0.05),而TPO组小鼠各波PL延长不明显,从对照组到HIBD+TPO组到HIBD组,BAEP各波PL逐组延长。结论:TPO能够减轻HIBD新生小鼠的神经细胞损伤,改善其听觉功能发育,其机制可能与稳定神经细胞膜、抑制细胞内活性氧(ROS)生成、减少神经细胞凋亡有关。

Objective：To study the protective effect of thrombopoietin （TPO） on neuronal cells in neonatal mice with hypoxic-ischemic brain damage （HIBD）, and to explore its mechanism. Methods： The C57 mice（7-day-old） were divided into sham operation control group, model group （HIBD） and TPO treatment group （HIBD＋TPO）, after then, each group of mice for the corresponding experimental treatment. After three weeks, the following indicators of each test group were compared： pathological changes of brain tissue sections （HE staining）, immunohistochemical method of neuron-specific enolase （NSE） in situ expression, expression of reactive oxygen species （ROS） in frozen tissue of brain tissue, and the peak latency （PL） of brainstem auditory evoked potentials （BAEP）. Results ： Compared with the control group, the pathological changes of the brain tissue of HIBD group were obvious, the use of TPO could significantly re- duce the total amount of NSE release of intracellular to extracellular due to HIBD. And also significantly reduce the generation of reactive oxygen species in the cells during nerve cell injury. The peak latency （PL） duration of BAEP in HIBD group was significantly longer than that in control group （P%0. 05）, while TPO group mice＇s PL of BAEP were not significantly extended. Conclusion： TPO can reduce nerve cell damage in HIBD neonatal mice. And improve its auditory function development. The mechanism may be related to the stability of nerve cell membrane,inhibition of intracellular reactive oxygen species （ROS） generation,reduce neuronal apoptosis.