ERK1／2信号途径对大鼠弥漫性脑创伤后神经细胞凋亡的调控机制

Regulating effects of the ERK1/2 signaling pathway on neurons apoptosis after diffuse brain injury in rats

目的探讨脑创伤后ERK1／2信号调控神经细胞凋亡的分子机制。方法sD大鼠分为正常对照组、模型组、抑制剂U0126高、低剂量组。Marmarou’s法制作弥漫性脑创伤模型。光镜下观察伤后神经细胞形态变化；免疫组化和WesternBlot法检测伤后磷酸化ERK1／2水平和Bax表达；TUNEL法检测凋亡细胞。结果与正常对照组比较，模型组海马区部分神经细胞出现变性坏死和凋亡改变，磷酸化ERK1／2、Bax表达增高，神经细胞凋亡数目增多（P〈0．05）；U0126治疗后，脑组织形态损伤程度、磷酸化ERK1／2和Bax表达、神经细胞凋亡数目回降，上述变化在U0126高剂量组中更为显著。结论脑创伤后活化的ERK1／2信号通过调控Bax表达在神经细胞凋亡过程中发挥重要作用。

Objective To investigate the regulating mechanisms of extracellular signal - regulated kinase 1/2 signaling pathway on the neuron apoptosis after diffuse brain injury（DBI） in rats and provide basic of treatment. Method Male Sprague - Dawley rats were randomly divided into four groups ： control group, model group, low dose of inhibitor U0126 treatment group and high dose of inhibitor U0126 treatment group. DBI rat model was established according to the description of Marmarou diffused brain injury. The changes of neuron morphous were observed with light microscopy. The level of ERK1/2 phosphorylation and Bax were measured by immunohistochemistry and Western -Blot. Apoptosis was measured with TUNEL method. Results Compared to control group, some neurons displayed histopathologic changes of necrosis. The expression levels of ERK1/2 phosphorylation, Bax and number of apoptotic nerve cell increased（ P 〈 0. 05）. After treatment with U0126, the ERK1/2 Phosphorylation, Bax expressions and number of apoptotic nerve cell were significantly decreased especially in high dose of U0126 group （P 〈 0.05 ） . Conclusions After DBI, The activated ERK1/2 signaling pathway plays an important role in process of nerve cell apoptosis by regulating Bax expression.