葛根素通过抑制 p38MAPK 信号通路抑制细颗粒物诱导的血管平滑肌细胞增殖。
Puerarin inhibits vascular smooth muscle cells proliferation induced by fine particulate matter via suppressing of the p38 MAPK signaling pathway.
机构信息
Department of Medical Cardiology, the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, China.
Respiratory Medicine, the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, China.
出版信息
BMC Complement Altern Med. 2018 May 4;18(1):146. doi: 10.1186/s12906-018-2206-9.
BACKGROUND
Fine particulate matter (PM2.5) is a major risk factor for the development and progression of atherosclerosis. Proliferation and infiltration of vascular smooth muscle cells (VSMCs) from the blood vessel media into the intima is a crucial step in the pathophysiology of atherosclerosis. Puerarin, a natural extract from Radix Puerariae, possesses significant anti-atherosclerosis properties. However, the underlying molecular mechanisms responsible for the effect of puerarin on the VSMCs proliferation induced by PM2.5 remain unclear. The present study was designed to examine the effect of puerarin on PM2.5-induced VSMCs proliferation, and to explore the p38 mitogen-activated protein kinase (p38 MAPK) signal mechanism involved.
METHODS
VSMCs viability was measured by CCK-8 assay, VSMCs proliferation was assessed by BrdU immunofluorescence, the levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were assayed by colorimetric assay kits, the levels of nitric oxide (NO) and endothelin-1 (ET-1) were determined by nitrate reductase method and radioimmunoassay, the levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured by ELISA. The protein expressions of phospho-p38 MAPK (p-p38 MAPK) and proliferating cell nuclear antigen (PCNA) in the VSMCs were subjected by Western blot.
RESULTS
Compared to the PM2.5-treated cells, in addition to inhibiting the PM2.5-induced VSMCs proliferation, puerarin also down-regulated the protein expressions of p-p38 MAPK and PCNA, decreased the levels of ET-1, VCAM-1, IL-6, TNF-α and MDA, increased the levels of NO and SOD. Moreover, the anti-proliferative effects of puerarin were significantly enhanced by the co-incubation of puerarin with SB203580, a selective inhibitor of p38 MAPK, as compared to the puerarin-treated cells.
CONCLUSION
These results suggest that puerarin might suppress the PM2.5-induced VSMCs proliferation via the inhibition of the p38 MAPK signaling pathway.
背景
细颗粒物（PM2.5）是动脉粥样硬化发生和发展的主要危险因素。血管平滑肌细胞（VSMCs）从血管中层向内膜的增殖和浸润是动脉粥样硬化病理生理学的关键步骤。葛根素是葛根的天然提取物，具有显著的抗动脉粥样硬化作用。然而，葛根素对 PM2.5 诱导的 VSMCs 增殖的作用的潜在分子机制尚不清楚。本研究旨在探讨葛根素对 PM2.5 诱导的 VSMCs 增殖的影响，并探讨涉及的 p38 丝裂原活化蛋白激酶（p38 MAPK）信号机制。
方法
通过 CCK-8 法测定 VSMCs 活力，BrdU 免疫荧光法测定 VSMCs 增殖，比色法试剂盒测定超氧化物歧化酶（SOD）和丙二醛（MDA）水平，硝酸盐还原酶法和放射免疫法测定一氧化氮（NO）和内皮素-1（ET-1）水平，酶联免疫吸附法测定血管细胞黏附分子-1（VCAM-1）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平。Western blot 法检测 VSMCs 中磷酸化 p38 MAPK（p-p38 MAPK）和增殖细胞核抗原（PCNA）的蛋白表达。
结果
与 PM2.5 处理的细胞相比，除了抑制 PM2.5 诱导的 VSMCs 增殖外，葛根素还下调了 p-p38 MAPK 和 PCNA 的蛋白表达，降低了 ET-1、VCAM-1、IL-6、TNF-α和 MDA 的水平，增加了 NO 和 SOD 的水平。此外，与葛根素处理的细胞相比，葛根素与 p38 MAPK 选择性抑制剂 SB203580 共同孵育可显著增强其抗增殖作用。
结论
这些结果表明，葛根素可能通过抑制 p38 MAPK 信号通路抑制 PM2.5 诱导的 VSMCs 增殖。
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