中文摘要：

目的通过建立小鼠创伤性脑损伤（TBI）模型，研究丝裂原活化蛋白激酶（MAPKs）通路中的细胞外调节蛋白激酶1／2（ERK1／2）通路、JNK通路和p38通路的激活及在TBI中的作用及机制。方法建立小鼠TBI模型，通过Westernblot检测ERK1／2、JNK和p38的相对磷酸化水平，确定TBI后MAPK通路的激活情况；分别加入ERK1／2通路抑制剂（PD98059，500μmol／L）、JNK通路抑制剂（SP600125，500μmol／L）和p38通路抑制剂（SB203580，500μmol／L），通过脑干湿重检测、神经功能学评分和TUNEL染色评估不同抑制剂对TBI的作用，并通过Westernblot检测ERK1／2、JNK和p38的相对磷酸化水平，明确ERK1／2通路、JNK通路和p38通路之间的相互调节作用。结果TBI可分别引起ERK1／2通路、JNK通路和p38通路的激活；抑制ERK通路和JNK通路可减轻TBI引起的脑水肿、神经功能损伤和细胞凋亡，而抑制p38通路则加重TBI引起的脑水肿、神经功能损伤和细胞凋亡；抑制JNK通路可减少ERK1／2的相对磷酸化水平，而抑制p38通路可增加ERK1／2的相对磷酸化水平。结论TBI后，ERK1／2通路和JNK通路的激活发挥促进损伤形成的作用，而p38通路的激活则起到神经保护的作用；ERK1／2通路的激活受到JNK通路的促进和p38通路的抑制，表明MAPK通路之间存在相互调节。

英文摘要：

Objective To investigate the effect of mitogen-activated protein kinases （MAPK） pathways such as extracellular regulated protein kinases1/2 （ERK1/2） pathway, JNK pathway, and p38 pathway on traumatic brain injury （TBI） by using in vivo TBI model. Methods After TBI, phosphorylation of ERK1/2, JNK, and p38 was detected by Western blot; effects of ERK1/2 pathway inhibitor （PD98059, 500 μmol/L）, JNK pathway inhibitor （SP500125, 500μmol/L）, and p38 pathway inhibitor （SB2ff5580, 590 μmol/L） on TBI were measured by water content detection, neurological severity score, and TUNEL assay and interactions between MAPK pathways were determined by Western blot. Results TBI differentially activated ERK1/2 pathway, iNK pathway, and p38 pathway; inhibition of ERK1/2 pathway or JNK pathway attenuated TBI-induced brain edema, neurological deficits, and apoptosis, while inhibition of p38 pathway aggravated TBI-induced brain edema, neurological deficits, and apoptosis; inhibition of JNK pathway reduced the relative phosphorylation of ERK1/2, whereas inhibition of of p38 pathway elevated the relative phosphorylation of ERK1/2. Conclusion After TBI, activation of ERK1/2 pathway and JNK pathway protnotes the formtion of brain edema, neurological deficits, and apoptosis, while activation of p38 pathway plays a ncuroprotective role in TBI; activation of ERK1/2 pathway is promoted by JNK pathway but inhibited by p38 pathway, indicating that there are interactions between different MAPK pathways.