CAJ | 학술논문

目的研究水通道蛋白4(AQP4)在颅脑损伤性大鼠脑内的表达,及丝裂原活化蛋白激酶(MAPKs)信号转导通路阻滞剂 U0126对其表达的影响.方法 Feeney 法制作大鼠重型颅脑损伤模型,大鼠尾静脉注射药物 U0126,免疫电镜观察 AQP4的分布,测定脑组织含水量,并采用免疫组化法和荧光定量 PCR 检测 AQP4的表达.免疫组化法测定预先经尾静脉给予 U0126后MAPKs 信号通路关键蛋白细胞外信号调节激酶1/2(ERK1/2)和 cAMP 反应元件结合蛋白(CREB)的磷酸化水平,同时观察 U0126对脑水肿和 AQP4表达的影响.结果假手术组 AQP4表达较低,在损伤后表达升高,脑组织含水量增加,给予 U0126后 AQP4的表达和脑组织含水量降低,同时 ERK1/2磷酸化水平和 CREB 的磷酸化水平降低.结论颅脑损伤后 AQP4表达上升,脑水肿明显,给予 U0126可阻断 MAPKs 信号通路,抑制 AQP4的表达,减轻脑水肿.
목적연구수통도단백4(AQP4)재로뇌손상성대서뇌내적표체,급사렬원활화단백격매(MAPKs)신호전도통로조체제 U0126대기표체적영향.방법 Feeney 법제작대서중형로뇌손상모형,대서미정맥주사약물 U0126,면역전경관찰 AQP4적분포,측정뇌조직함수량,병채용면역조화법화형광정량 PCR 검측 AQP4적표체.면역조화법측정예선경미정맥급여 U0126후MAPKs 신호통로관건단백세포외신호조절격매1/2(ERK1/2)화 cAMP 반응원건결합단백(CREB)적린산화수평,동시관찰 U0126대뇌수종화 AQP4표체적영향.결과가수술조 AQP4표체교저,재손상후표체승고,뇌조직함수량증가,급여 U0126후 AQP4적표체화뇌조직함수량강저,동시 ERK1/2린산화수평화 CREB 적린산화수평강저.결론로뇌손상후 AQP4표체상승,뇌수종명현,급여 U0126가조단 MAPKs 신호통로,억제 AQP4적표체,감경뇌수종.
[ ] Objective To investigate the effect of MAPSs pathway inhibitor U0126 on cerebral edema and the expression of aquaporin 4 (AQP4) in rats after traumatic brain injury. Methods Severe traumatic brain injury was induced using the Feeny method in rats. U0126 was injected through caudal vein. The distribution of AQP4 was observed by immunoelectron microscopy. Water content was detected by dry-wet analysis. The expression of AQP-4 was detected by immunohistochemistry and re-al-time PCR. Phosphorylation of ERK1/2 and CREB was detected by immunohistochemistry. Results Compared with sham op-eration group, the water content and AQP4 expression in traumatic brain injury group were increased significantly. The water content and AQP4 expression in U0126 group were lower than those in brain injury group. Meanwhile, p-ERK1 /2 and p-ERCB in U0126 group were lower than those in brain injury group. Conclusion U0126 can inhibit the over-expression of AQP4 and re-duce the brain edema, which may be related to the block of MAPKs signal pathway.