Objective To investigate the impact of AG490 on the blood-brain barrier (BBB ) permeability and the expression of interleukin-6 (IL-6 )and tumor necrosis factor-α(TNF-α)after traumatic brain injury (TBI)in rats. Methods A total of 144 healthy male SD rats were randomly divided into a control group,a trauma group,and an AG490 intervention group (n=48 in each group). The rats in each group were redivided into four subgroups (4 h,1 d,3 d,and 7 d subgroups)according to the time points after cerebral injury (n=12 in each subgroup). A brain trauma models were induced by hydraulic shock method. Evans blue was used to determine the changes of the BBB permeability after cerebral injury in each group. Real-time fluorescence quantitative PCR was to detect the expression levels of TNF-αand IL-6 mRNA in rat brain tissue. Immunohistochemistry was used to detect the expression of human phospho tyrosine kinase (P-JAK2). Results (1)The permeability of BBB:The permeability of BBB increased at 4 h,1 d,3 d and 7 d after brain injury in the trauma group (Evans blue permeation:10. 4 ± 1. 2,16. 0 ± 1. 4,22. 3 ± 2. 0,and 8. 4 ± 0. 9μg/g,respectively). Compared with the control group, there were significant differences (all P<0. 01). The Evans blue permeation of the AG490 intervention group were 9. 1 ± 1. 0,12. 8 ± 1. 1,17. 5 ± 1. 4 and 7. 1 ± 0. 8μg/g,respectively at each time point,and they were all significantly lower than those of the trauma group (all P<0. 01). (2)The expression of IL-6 and TNF-α mRNA:The expression levels of IL-6 mRNA and TNF-α mRNA at 4 h,1 d,3 d and 7 d after traumatic brain injury in the trauma group were 2. 31 ± 0. 35,2. 73 ± 0. 35,3. 32 ± 0. 29,2. 14 ± 0. 24 and 7. 46 ± 1. 18,9. 42 ± 1. 54,13. 76 ± 1. 89,and 6. 28 ± 1. 00,respectively,they were all significantly higher than those of the control group (all P<0. 01). The expression levels of IL-6 mRNA and TNF-α mRNA of the AG490 intervention group were 1. 14 ± 0. 22,1. 54 ± 0. 23,1. 94 ± 0. 32,1. 26 ± 0. 21 and 5. 57 ± 0. 88, 7. 78 ± 1. 02,11. 51 ± 1. 29,and 5. 05 ± 0. 97,respectively,they were all lower than those of the trauma group,but they still higher than the control group. There were significant differences (all P<0. 01). (3 )The expression of P-JAK2:The expression levels of P-JAK2-positive cells at each time point after traumatic brain injury in the trauma group were significantly higher than the control group (all P<0. 01),they were 17. 4 ± 2. 7,56. 2 ± 6. 7,26. 1 ± 5. 4,and 15. 3 ± 2. 5,respectively;those of the AG490 intervention group were 12. 2 ± 1. 4,41. 5 ± 4. 6,19. 4 ± 4. 1,and 9. 6 ± 2. 0,respectively,they were all lower than those of the trauma group,but still higher than the control group. There were significant differences (all P<0. 01). Conclusion During the acute phase after TBI,AG490 may activate the factor signaling pathways by inhibiting the non-receptor tyrosine kinase/signal transduction and transcription,significantly inhibit the expression of brain tissue inflammatory cytokines IL-6 IL-6 and TNF-α,reduce the BBB damage,and help to reduce secondary brain injury.%目的：探讨AG490对大鼠创伤性脑损伤（TBI）后血-脑屏障通透性以及炎性因子IL-6、TNF-α表达变化的影响。方法取健康成年雄性SD大鼠144只，按照随机数字表法分为对照组、创伤组、AG490干预组各48只，每组又分为4个亚组，分别对应伤后4 h、1 d、3 d、7 d时间点，每亚组各12只大鼠。应用液压冲击法制作脑创伤模型。应用伊文思蓝渗透法检测各组大鼠脑创伤后血-脑屏障通透性改变情况；采用实时荧光定量PCR方法检测大鼠脑组织中IL-6及TNF-α mRNA表达水平；免疫组化检测磷酸化酪氨酸激酶-2（P-JAK2）的表达。结果（1）血-脑屏障通透性：脑损伤后4h、1d、3d、7d，创伤组血-脑屏障通透性增加[创伤脑组织伊文思蓝渗透量分别为（10.4±1.2）、（16.0±1.4）、（22.3±2.0）、（8.4± 0.9）μg／g湿脑组织]，与对照组相比，差异均有统计学意义（均P＜0.01）。AG490干预组各时间段伊文思蓝渗透量分别为（9.1±1.0）、（12.8±1.1）、（17.5±1.4）、（7.1±0.8）μg／g湿脑组织，均明显低于创伤组（均 P＜0.01）。（2）IL-6 mRNA及TNF-αmRNA表达：脑创伤后4 h、1 d、3 d、7 d，创伤组IL-6 mRNA及TNF-αmRNA表达量分别为2.31±0.35、2.73±0.35、3.32±0.29、2.14± 0.24和7.46±1.18、9.42±1.54、13.76±1.89、6.28±1.00，均明显高于对照组（均P＜0.01）；AG490干预组IL-6 mRNA及TNF-α mRNA表达量分别为1.14± 0.22、1.54± 0.23、1.94± 0.32、1.26±0.21和5.57±0.88、7.78±1.02、11.51±1.29、5.05±0.97，均低于创伤组，但仍高于对照组，差异均有统计学意义（均P＜0.01）。（3）P-JAK2的表达：脑创伤后各时间点，创伤组P-JAK2阳性细胞表达量均明显高于对照组（均P＜0.01），分别为17.4± 2.7、56.2±6.7、26.1±5.4、15.3±2.5；AG490干预组分别为12.2±1.4、41.5±4.6、19.4± 4.1、9.6±2.0，均低于创伤组，但仍高于对照组，差异均有统计学意义（均P＜0.01）。结论 TBI后急性期，AG490可通过抑制非受体型酪氨酸蛋白激酶／信号传导及转录激活因子信号通路，明显抑制脑组织炎性因子IL-6及TNF-α的表达，减轻血-脑屏障的破坏，有助于减轻继发性脑损伤。
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