Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China.
Cell Biochem Biophys. 2013 May;66(1):121-30. doi: 10.1007/s12013-012-9460-0.
Evidence from ground-based animal studies using tail-suspended hindlimb unloaded rats model has clearly demonstrated that simulated microgravity-induced smooth muscle cell phenotype conversion, a characteristic vascular structural and functional remodeling, may be one of the key contributors to postspaceflight orthostatic intolerance. However, the rats model involves multiple collective effects of microgravity including cephalic fluid shift and postural muscle unloading on smooth muscle cells (SMCs). It cannot isolate a single factor from the collective ones and therefore is not ideal to study the effects of gravitational vector alteration alone on SMCs. To test the hypothesis that gravitational vector alteration per se might affect smooth muscle cell phenotype, a roller culture apparatus was employed to expose cultured rat aortic smooth muscle cells (RASMCs) to simulated microgravity. Cell proliferation, cell cycle distribution, apoptosis, migration, and nitric oxide production rates were measured and compared between the control and the simulated microgravity groups. Cell cytoskeleton reorganization induced by simulated microgravity was observed by confocal microscopy. Specific contractile and synthetic Gene expression at the mRNA level was quantified by reverse transcriptional polymerase chain reaction. It was observed that simulated microgravity suppressed RASMC proliferation and migration, enhanced cell apoptosis, stimulated NO release, and destroyed the original well-organized cytoskeleton. Moreover, at the mRNA level, long-time exposure (≥ 72 h) to simulated microgravity induced a contractile phenotype tendency by up-regulating smMHC expression. All these findings suggest that the phenotype modulation of vascular smooth muscle cells may be gravity dependent.
地面动物实验研究采用尾部悬吊后肢去负荷大鼠模型，清楚地表明，模拟微重力引起的平滑肌细胞表型转化，是血管结构和功能重塑的特征之一，可能是航天后体位不耐受的关键因素之一。然而，该大鼠模型涉及微重力的多个综合效应，包括头部液体移位和姿势性肌肉去负荷对平滑肌细胞（SMC）的影响。它不能将单一因素从综合因素中分离出来，因此，研究重力矢量改变单独对 SMC 的影响并不理想。为了验证重力矢量改变本身可能影响平滑肌细胞表型的假设，采用滚轴培养装置使培养的大鼠主动脉平滑肌细胞（RASMC）暴露于模拟微重力环境中。在对照组和模拟微重力组之间测量并比较细胞增殖、细胞周期分布、细胞凋亡、迁移和一氧化氮（NO）产生率。通过共聚焦显微镜观察模拟微重力诱导的细胞骨架重排。通过反转录聚合酶链反应定量分析收缩和合成基因在 mRNA 水平上的表达。结果表明，模拟微重力抑制 RASMC 的增殖和迁移，增强细胞凋亡，刺激 NO 释放，并破坏原有的组织良好的细胞骨架。此外，在 mRNA 水平上，长时间（≥72 小时）暴露于模拟微重力可通过上调 smMHC 表达诱导收缩表型倾向。所有这些发现表明，血管平滑肌细胞的表型调节可能依赖于重力。
