整合素信号转导通路参与模拟失重引起的血管适应性变化

Integrin signaling pathway is involved in adaptive changes of blood vessels induced by simulated weightlessness

目的本研究将模拟失重大鼠整体实验与离体血管灌流培养实验相结合,重点观察在不同跨壁压条件下整合素(integrin)及其关联的信号转导分子的表达、激活、募集等变化规律。方法整体实验:大鼠尾部悬吊法模拟失重4周(SUS组),并设同步对照组(CON组)。观察模拟失重对大鼠IntegrinαV、Integrinβ3、Src、ERK和p-ERK蛋白表达的影响。血管培养实验:建立可以控制流量、压力的血管培养系统。结果悬吊组与对照组相比,颈总动脉IntegrinαV、Src和p-ERK蛋白表达显著上调(P<0.05),而Integrinβ3和ERK蛋白表达无显著性差异。在血管培养实验中,与常压组(80 mm Hg)相比,高压(150 mm Hg)灌流可引起IntegrinαV、Integrinβ3、Src、ERK和p-ERK升高(P<0.05),但在3 d的高压灌流期间,如每天1 h使灌流压降为80 mm Hg,则上述改变即可被部分改善,即IntegrinαV、Integrinβ3和Src蛋白表达恢复至接近常压(80 mm Hg)水平。结论跨壁压分布变化是失重引起动脉区域性重构的始动原因;但每日只要短时间使其恢复常压,血管重构及整合素下游分子的变化即可被部分防止。

AIM To observe expression, activation and recruitment of integrin changes and associated signal transducfion molecules under different transmural pressures by combining simulated weightlessness treatment and vascular perfusion culture. METHODS Whole animal level： Effects of simulated weight- lessness on the expressions of integrin αV, integrin β3, Sre, ERK and p-ERK were observed. Blood vessel level： The pressure vessel culture system that could control the flow rate and pressure was established. RESULTS Westem blot analysis revealed that an increased expression of integrin αV, Src and p-ERK was observed by tail suspension. No significant difference in integrin β3 and ERK protein expression was detected. High pressure culture of 150 mmHg induced significant protein expression of integrin aV, integrin β3, Sre, ERK and p-ERK in carotid artery. Daily 1-h normal pressure recovery of 80 mmHg partly restored the changes of integrin αV, integrin β3 and Src expression. CONCLUSION Redistribution of transmural pressures may be the primary factor that initiates region-specific remodeling of arteries during microgravity. Daily 1-h normal pressure recovery partly prevents vascular remodeling and changes of integrin downstream molecules.