姜黄素通过激活 miR-22 抑制血管平滑肌细胞的增殖、迁移和新生内膜形成。
Curcumin inhibits proliferation, migration and neointimal formation of vascular smooth muscle via activating miR-22.
机构信息
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Cardiovascular Department, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
出版信息
Pharm Biol. 2020 Dec;58(1):610-619. doi: 10.1080/13880209.2020.1781904.
Curcumin has antitumor, antioxidative, anti-inflammatory, and anti-proliferative properties. To investigate the role of miR-22 during curcumin-induced changes in vascular smooth muscle cells (VSMC) and neointima formation in balloon-injured rat abdominal aorta. Sprague-Dawley rats were randomised to the sham-operated ( = 10), operated control (injured, = 10), and curcumin treatment ( = 10) groups. miR-22 expression was determined by real-time PCR. SP1 was assessed by western blot and real-time PCR. Rat aortic smooth muscle A7r5 cells were used to determine VSMC proliferation and migration, which were measured by the MTS, EdU staining, Transwell, and wound healing assays. miR-22 levels declined following arterial balloon injury (48% at 3d, < 0.05) and serum stimulation (45% at 24 h, < 0.01). Functional studies revealed that miR-22 negatively regulated the proliferation and migration of VSMCs by directly targeting the SP1 transcription factor in VSMCs. Curcumin increased the expression of miR-22 (81%, < 0.05) and decreased the protein expression of SP1 in VSMCs (25%, < 0.05). miR-22 inhibition was found to attenuate the effects of curcumin on VSMC functions. Curcumin increased miR-22 (46%, < 0.01), decreased the SP1 protein (19%, < 0.05), and inhibited vascular neointimal area (48%, < 0.01) . The miR-22/SP1 pathway is involved in the protective role of curcumin during arterial balloon injury, but the mechanisms remain unclear. miR-22 is involved in the inhibitory effects of curcumin on VSMCs' proliferation, migration and neointima hyperplasia after arterial balloon injury in rats. Curcumin could be used to prevent neointimal hyperplasia after angioplasty.
姜黄素具有抗肿瘤、抗氧化、抗炎和抗增殖作用。为了研究 miR-22 在姜黄素诱导的血管平滑肌细胞（VSMC）变化和球囊损伤大鼠腹主动脉新生内膜形成中的作用。将 Sprague-Dawley 大鼠随机分为假手术组（n=10）、手术对照组（损伤，n=10）和姜黄素治疗组（n=10）。通过实时 PCR 测定 miR-22 的表达。通过 Western blot 和实时 PCR 评估 SP1。使用大鼠主动脉平滑肌 A7r5 细胞来确定 VSMC 的增殖和迁移，通过 MTS、EdU 染色、Transwell 和划痕愈合测定来测量。动脉球囊损伤后 miR-22 水平下降（3d 时 48%，<0.05）和血清刺激（24h 时 45%，<0.01）。功能研究表明，miR-22 通过直接靶向 VSMCs 中的 SP1 转录因子负调控 VSMCs 的增殖和迁移。姜黄素增加 miR-22 的表达（81%，<0.05）并降低 VSMCs 中 SP1 的蛋白表达（25%，<0.05）。发现 miR-22 抑制可减弱姜黄素对 VSMC 功能的影响。姜黄素增加 miR-22（46%，<0.01），降低 SP1 蛋白（19%，<0.05），并抑制血管新生内膜面积（48%，<0.01）。miR-22/SP1 通路参与了姜黄素在动脉球囊损伤中的保护作用，但机制尚不清楚。miR-22 参与了姜黄素对大鼠动脉球囊损伤后 VSMC 增殖、迁移和新生内膜增生的抑制作用。姜黄素可用于预防血管成形术后的新生内膜增生。
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