Objective To investigate the effect of mitogen activated protein kinase / extracellular signal-regulated kinase (MEK / ERK)1 / 2 signaling pathway on early brain injury (EBI)following experimental subarachnoid hemorrhage (SAH)in rats. Methods Sixty male SD rats were randomly divided into a control group and a 1,6,12,24,48,or 72 h group after SAH modeling. SAH + MEK inhibitor U0126 was used to intervene the 24,48,and 72 h groups (a total of 10 groups;n = 6 in each group). In addition to the control group,blood was injected into the cisterna magna of the rats to induce a SAH model in another 9groups. The blood samples were taken from infraorbital venous plexus. Enzyme-linked immune sorbent assay (ELISA)was used to detect the levels of interleukin-6 (IL-6),IL-1β,and tumor necrosis factor α(TNF-α)in each group. Evans blue content in brain tissue was used to evaluate the blood-brain barrier damage. Western blot was used to detect the levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/ 2)and matrix metalloproteinase-9 (MMP-9)proteins in basilar artery tissue,and compared them. Results Compared with the control group at the same time points,there were significant differences in the levels of IL-6 and IL-1β at 6,12,24,48,and 72h after modeling in the SAH group (all P <0. 05). At 12,24, 48,and 72 h after modeling,the expression levels of p-ERK1/ 2 protein of the basilar artery tissue of the SAH group were 0. 73 ± 0. 09,0. 85 ± 0. 12,0. 94 ± 0. 09,and 0. 96 ± 0. 09,respectively,they were significantly higher than those of the control group (all P < 0. 05). At 48 and 72 h after modeling in the SAH group,the level of MMP-9 protein was significantly higher than that in the control group (1. 27 ± 0. 15 vs. 0. 68 ± 0. 08,2. 41 ± 0. 11 vs. 0. 71 ± 0. 14). At 72 h after modeling,the Evans blue content in brain tissue of the SAH group was significantly higher than that of the control group (15. 3 ± 2. 2 μg/ g vs. 2. 7 ± 0. 4 μg/ g). After giving the MEK inhibitor U0126 intervention,the levels of serum IL-6,IL-1β,and TNF-α at 24,48, and 72 h after modeling,and the expression levels of p-ERK1 / 2 and MMP-9 proteins at 48 and 72 h (p-ERK1 / 2:0. 76 ± 0. 07,0. 81 ± 0. 06;MMP-9:0. 92 ± 0. 14,1. 79 ± 0. 16),and the Evans blue content (8. 9 ± 1. 7 μg / g)in brain tissue at 72 h after modeling were significantly lower than those of the SAH group (P < 0. 05). Conclusion The MEK/ ERK1/ 2 signal pathway may be closely associated with the inflammatory reaction and blood-brain barrier damage after SAH,which suggests that the intervention of the MEK/ ERK1 / 2 signal pathway may be a potential target for the prevention of early brain injury after SAH.%目的探讨丝裂原激活蛋白激酶／细胞外信号调节激酶（MEK／ ERK）1／2信号通路在大鼠实验性蛛网膜下腔出血（SAH）后早期脑损伤中的作用。方法取成年雄性SD大鼠60只，随机分为对照组， SAH 造模后1、6、12、24、48、72 h 组，SAH ＋ MEK 抑制剂U0126干预24、48、72 h组，共10组，每组6只。除对照组外，另9组大鼠于枕大池注血制备SAH 模型，于眶下静脉丛取血。采用酶联免疫吸附法测定各组血清白细胞介素6（IL-6）、IL-1β、肿瘤坏死因子α（TNF-α）含量，脑组织伊文思蓝含量测定评定血-脑屏障损伤，Western-blot法测定基底动脉组织中磷酸化细胞外信号调节激酶（p-ERK1／2）、基质金属蛋白酶9（MMP-9）蛋白的水平并加以比较。结果 SAH 组大鼠造模后6、12、24、48、72 h，血清IL-6、IL-1β水平与对照组同一时间点比较，差异均有统计学意义（均P ＜0.05）；造模后24、48、72 h，SAH组大鼠血清TNF-α水平均高于对照组，差异均有统计学意义（均P ＜0.05）。造模后12、24、48、72 h，SAH组大鼠基底动脉组织p-ERK1／2蛋白表达水平分别为0.73±0.09、0.85±0.12、0.94±0.09、0.96±0.09，均明显高于对照组，差异均有统计学意义（均P ＜0.05）。SAH组造模后48、72 h，MMP-9蛋白水平明显高于对照组（1.27±0.15比0.68±0.08、2.41±0.11比0.71±0.14）。造模后72 h，SAH 组脑组织伊文思蓝含量明显高于对照组[（15.3±2.2）μg／ g比（2.7±0.4）μg／ g]。给予MEK抑制剂U0126干预后，造模后24、48、72 h血清IL-6、IL-1β、TNF-α水平，造模后48、72 h p-ERK1／2、MMP-9蛋白表达水平（p-ERK1／2：0.76±0.07、0.81±0.06；MMP-9：0.92±0.14、1.79±0.16），以及造模后72 h脑组织伊文思蓝含量[（8.9±1.7）μg ／ g]均明显低于SAH 组，差异均有统计学意义（均P ＜0.05）。结论 MEK／ ERK1／2信号通路与大鼠实验性SAH后炎性反应及血-脑屏障损伤密切相关，提示干预MEK／ ERK1／2信号通路可能为预防SAH后早期脑损伤的潜在靶点。
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