Liu Huan, Wang Zhong-Chao, Bai Yun-Gang, Cai Yue, Yu Jin-Wen, Zhang Hai-Jun, Bao Jun-Xiang, Ren Xin-Ling, Xie Man-Jiang, Ma Jin
Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China.
Clin Exp Pharmacol Physiol. 2015 May;42(5):510-9. doi: 10.1111/1440-1681.12381.
Microgravity-induced vascular remodelling may play an important role in post-spaceflight orthostatic intolerance. In this study, we aimed to investigate the effects of simulated microgravity on monocyte adhesion to aortic endothelium in hindlimb unweighted rats and to elucidate the underlying mechanisms associated with this event. Sprague-Dawley rats were subjected to 4-week hindlimb unweighting to simulate microgravity. The recruitment of monocytes to the abdominal aorta was investigated by en face immunofluorescence staining and monocyte binding assays. The expression of the adhesion molecules E-selectin and vascular cell adhesion molecule-1 as well as the cytokine monocyte chemoattractant protein (MCP)-1 was evaluated by immunohistochemical staining, western blot, and quantitative reverse transcription polymerase chain reaction analyses. Additionally, nuclear factor-κB (NF-κB) activation and the messenger RNA expression levels of E-selectin, vascular cell adhesion molecule-1, and MCP-1 were assessed with the administration of an NF-κB inhibitor, pyrrolidine dithiocarbamate. Results showed that simulated microgravity significantly increased monocyte recruitment to the aortic endothelium, protein expression of E-selectin and MCP-1, and NF-κB activation in the abdominal aorta of rats. Pyrrolidine dithiocarbamate treatment not only significantly inhibited NF-κB activity but also reduced the messenger RNA levels of E-selectin, vascular cell adhesion molecule-1, and MCP-1 as well as monocyte recruitment in the abdominal aorta of hindlimb unweighted rats. These results suggest that simulated microgravity increases monocyte adhesion to rat aortic endothelium via the NF-κB-mediated expression of the adhesion molecule E-selectin and the cytokine MCP-1. Therefore, an NF-κB-mediated inflammatory response may be one of the cellular mechanisms responsible for arterial remodelling during exposure to microgravity.
微重力诱导的血管重塑可能在航天后体位性不耐受中起重要作用。在本研究中，我们旨在研究模拟微重力对后肢去负荷大鼠单核细胞与主动脉内皮黏附的影响，并阐明与此事件相关的潜在机制。将Sprague-Dawley大鼠进行4周的后肢去负荷以模拟微重力。通过面免疫荧光染色和单核细胞结合试验研究单核细胞向腹主动脉的募集。通过免疫组织化学染色、蛋白质印迹和定量逆转录聚合酶链反应分析评估黏附分子E-选择素和血管细胞黏附分子-1以及细胞因子单核细胞趋化蛋白(MCP)-1的表达。此外，通过给予NF-κB抑制剂吡咯烷二硫代氨基甲酸盐评估核因子-κB(NF-κB)的激活以及E-选择素、血管细胞黏附分子-1和MCP-1的信使核糖核酸表达水平。结果显示，模拟微重力显著增加了大鼠腹主动脉中单核细胞的募集、E-选择素和MCP-1的蛋白表达以及NF-κB的激活。吡咯烷二硫代氨基甲酸盐处理不仅显著抑制了NF-κB活性，还降低了后肢去负荷大鼠腹主动脉中E-选择素、血管细胞黏附分子-1和MCP-1的信使核糖核酸水平以及单核细胞的募集。这些结果表明，模拟微重力通过NF-κB介导的黏附分子E-选择素和细胞因子MCP-1的表达增加单核细胞与大鼠主动脉内皮的黏附。因此，NF-κB介导的炎症反应可能是微重力暴露期间动脉重塑的细胞机制之一。
