Effect of mitogen activated protein kinase/extracellular signal-regulated kinase 1/2 signaling pathway on early brain injury following subarachnoid hemorrhage in rats / 中国脑血管病杂志

ABSTRACT

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 / 20. 76 ± 0. 07,0. 81 ± 0. 06;MMP-90. 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.