Yuan Ming, Jiang Shi-zhong, Li Zhi-li, Liang Wen-bin
Space Med Med Eng (Beijing). 2004 Feb;17(1):24-9.
To study changes of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in femoral arteries of tail-suspended rats and their effects on contractility.
Microgravity was simulated by elevating the hindquarters of Wistar rats to produce hindlimb unweighting (HU). In the absence or presence of prazosin and PD98059 respectively, isometric tension of vessel rings from femoral arteries in response to norepinephrine (NE) was determined by in vitro perfusion technique; Basal total ERK1/2 level and phosphorylated ERK1/2 level stimulated by norepinephrine in the absence or presence of prazosin and PD98059 respectively were detected by Western blotting-enhanced chemically lightening system.
The maximal contractile response to NE was significantly lower in femoral arterial rings from 14 day-HU rats as compared with those in control rats. PD98059 caused a marked inhibition of NE-induced maximum contractile response in both control and HU femoral arterial rings. Moreover, the effect of inhibition was more significant in control rats than that in HU rats. Prazosin caused a right shift of the concentration-response curves (CRCs) to NE in both control and HU rats, but no difference was found between the two groups for the PA2 of prazosin calculated by Schild analysis, which showed that the sensitivity of alpha1 adrenoceptor was not changed by HU. After 7d-recovery, the difference of contractile response of femoral arterial rings to NE between recovered group and control group was nonsignificant. Data from Western blotting showed that basal total ERK1/2 levels were elevated in femoral arterial rings from 14d-HU rats as compared with those in control rats, but the levels of basal and NE-stimulated phosphorylated ERK1/2 were higher in control as compared with HU rats. After 7d recovery, the basal total ERK1/2 level and phosphorylated ERK1/2 level were not different from control.
Microgravity simulated by 14d-HU can induce abnormality of MAPK/ERK pathway, which may contribute to declined contractile response of femoral vessel rings to NE.
研究尾部悬吊大鼠股动脉中细胞外信号调节激酶1和2（ERK1/2）的变化及其对收缩性的影响。
通过抬高Wistar大鼠后躯模拟微重力，造成后肢失重大鼠模型（HU）。分别在有无哌唑嗪和PD98059的情况下，采用体外灌注技术测定股动脉血管环对去甲肾上腺素（NE）的等长张力；分别在有无哌唑嗪和PD98059的情况下，采用蛋白质免疫印迹增强化学发光系统检测基础状态下ERK1/2总量以及去甲肾上腺素刺激后的磷酸化ERK1/2水平。
与对照组相比，14天HU大鼠股动脉环对NE的最大收缩反应显著降低。PD98059显著抑制了对照组和HU组股动脉环中NE诱导的最大收缩反应。此外，对照组的抑制作用比HU组更显著。哌唑嗪使对照组和HU组对NE的浓度-反应曲线（CRCs）右移，但通过Schild分析计算的哌唑嗪PA2在两组间无差异，表明HU未改变α1肾上腺素能受体的敏感性。7天恢复后，恢复组和对照组股动脉环对NE的收缩反应差异不显著。蛋白质免疫印迹数据显示，与对照组相比，14天HU大鼠股动脉环中基础ERK1/2总量升高，但基础状态及NE刺激后的磷酸化ERK1/2水平在对照组中高于HU组。7天恢复后，基础ERK1/2总量和磷酸化ERK1/2水平与对照组无差异。
14天HU模拟的微重力可诱导丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）通路异常，这可能导致股血管环对NE的收缩反应下降。
