Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an 710032, China.
Military Medical Innovation Center, Fourth Military Medical University, Xi'an 710032, China.
Int J Mol Sci. 2023 Sep 26;24(19):14531. doi: 10.3390/ijms241914531.
Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts' health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague-Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights.
心血管衰老已被报道在航天飞行中加速，这对宇航员的健康和表现构成了巨大的潜在风险。然而，目前的运动方案不足以逆转微重力暴露的不利影响。最近，红景天苷（SAL），一种有价值的药用植物，已被证明在心血管和其他疾病的预防和治疗方面发挥着重要作用。在本工作中，使用四周尾部悬吊后肢去负荷的 SD 大鼠来模拟微重力对心血管系统的影响。我们发现，SAL 经胃内给药不仅显著降低了衰老生物标志物（如 P65 和 P16）的表达，而且还明显增加了血管平滑肌细胞（VSMCs）中 BK 依赖性凋亡基因的表达，包括大电导钙激活钾通道（BK）、Bax、Bcl-2 和 cleaved caspase-3，无论是在体内还是体外。此外，还筛选了相对非编码 RNA，并通过荧光素酶测定鉴定出 SAL 通过激活 LncRNA-FLORPAR、抑制 miR-193 来增加细胞凋亡，从而触发 BK-α 亚基的活性。我们的工作表明，SAL 是一种新型的非编码 RNA 调节剂，可调节 LncRNA-FLORPAR 海绵 miR-193 通路，显著促进了模拟微重力暴露期间 BK 依赖性凋亡和脑血管衰老样重塑。我们的研究结果可能为未来航天飞行中预防心血管衰老提供新的方法。
