褪黑素对大鼠失血性休克心肌的保护作用及对MEK/ERK通路的影响

Effect of Melatonin on Myocardial Protection and MEK/ERK Signaling Pathway in Rats after Hemorrhagic Shock

目的探讨褪黑素(MT)对大鼠失血性休克心肌的保护作用及其机制。方法将40只健康成年大鼠随机分为4组,MT干预组采用股动脉放血法制作放血休克模型,并经颈外静脉注射MT(2 mg.kg-1);溶剂对照组制作放血休克模型并注射含0.5%乙醇的0.9%氯化钠溶液(10 mg.kg-1);休克模型组制作放血休克模型但不注射任何试剂;假手术对照组进行单纯血管分离。采用ELISA法检测各组大鼠血清TNF-α、ICAM-1含量,免疫沉淀法纯化蛋白并测定ERK活性;Western-blot法测定p-ERK1/2和p-MEK1/2表达。结果MT干预组大鼠休克后TNF-α、ICAM-1含量均明显低于溶剂对照组和模型组(均P<0.01),ERK活性及p-ERK1/2、p-MEK1/2表达亦均明显低于溶剂对照组和模型组(均P<0.01)。结论MT对失血性休克心肌有保护作用,作用机制与下调MEK/ERK通路活性有关。

Objective To investigate the effect and the underlying mechanism of melatonin on myocardial protection in rats after hemorrhagic shock . Methods 40 healthy rats were randomlized into 4 groups. The rat model of hemorrhagic shock was established by bleeding from femoral artery. Then the rats were injected through the external carotic vein with 2 mg·kg^-1 MT in MT-treated group, 0.9% sodium chloride containing 0. 5% ethanol （ 10 mg·kg^-1 ） in the control group and nothing in shock model group. The rats in sham-opertated group received simple vasular dissection. The contents of TNF-α and ICAM-1 were studied by ELISA. ERK activity was measured by immuno-precipitation; p-ERK1/2 and p-MEK1/2 expressions were assessed by Western blot. Results Melatonin can inhibit the increases of TNF-α and ICAM-1 in myocardium after hemorrhagic shock. What＇s more, the intracellular ERK activity, p-ERK1/2 and p-MEK1/2 expressions were decreased by melatonin. Conclusion Melatonin has protective effect on myocardium after hemorrhagic shock, the mechanism was related with down-regulation of MEK/ERK signaling pathway.