富氢生理盐水通过抑制 ROS 和 TNF-α/NF-κB 通路预防颈动脉球囊损伤后的新生内膜形成。

Hydrogen-rich saline prevents neointima formation after carotid balloon injury by suppressing ROS and the TNF-α/NF-κB pathway.

机构信息

Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.

出版信息

Atherosclerosis. 2012 Feb;220(2):343-50. doi: 10.1016/j.atherosclerosis.2011.11.002. Epub 2011 Nov 11.

DOI:10.1016/j.atherosclerosis.2011.11.002

PMID:22153150

Abstract

BACKGROUND

Reactive oxygen species (ROS) play a pivotal role in neointima hyperplasia after balloon injury. Molecular hydrogen has emerged as a novel antioxidant and has been proven effective in treating many diseases.

OBJECTIVES

We aimed to determine the mechanism by which hydrogen affects neointima formation.

METHODS

We assessed the influence of a hydrogen-rich saline solution (HRSS) by daily injection in rats. Rats were euthanized to evaluate the neointima. ROS, malondialdehyde (MDA) and superoxide dismutase (SOD) and reduced glutathione (GSH), were detected in the injured artery. Macrophage infiltration and the production of inflammatory factors (i.e., IL-6, TNF-α and NF-κB) were also observed. The in vitro effects of hydrogen on vascular smooth muscle cell (VSMC) proliferation were also measured.

RESULTS

HRSS decreased the neointima area significantly. The neointima/media ratio was also reduced by HRSS. There was a decline in the number of PCNA-positive cells in the intima treated with HRSS. Meanwhile, HRSS ameliorated the ROS and MDA levels and increased SOD, reduced GSH levels in the injured carotid. In addition, the levels of inflammatory factors, such as IL-6, TNF-α and NF-κB p65, were attenuated by HRSS. In vitro studies also confirmed the anti-proliferative capability of the hydrogen solution and ROS generation in VSMCs induced by PDGF-BB.

CONCLUSION

HRSS may have a protective role in the prevention of neointima hyperplasia and restenosis after angioplasty. HRSS may partially exert its role by neutralizing the local ROS and suppressing the TNF-α/NF-κB pathway.

摘要

背景

活性氧（ROS）在球囊损伤后新生内膜增生中起关键作用。氢气作为一种新型抗氧化剂已经出现，并已被证明在治疗许多疾病方面有效。

目的

我们旨在确定氢气影响新生内膜形成的机制。

方法

我们通过每天给大鼠注射富氢生理盐水（HRSS）来评估 HRSS 的影响。处死大鼠以评估新生内膜。在损伤的动脉中检测 ROS、丙二醛（MDA）和超氧化物歧化酶（SOD）以及还原型谷胱甘肽（GSH）。还观察了巨噬细胞浸润和炎症因子（即 IL-6、TNF-α 和 NF-κB）的产生。还测量了氢气对血管平滑肌细胞（VSMC）增殖的体外影响。

结果

HRSS 显著降低新生内膜面积。HRSS 还降低了新生内膜/中膜比。与 HRSS 处理的内膜中的 PCNA 阳性细胞数量减少。同时，HRSS 改善了损伤颈动脉中 ROS 和 MDA 水平，并增加了 SOD、降低了 GSH 水平。此外，HRSS 还降低了炎症因子（如 IL-6、TNF-α 和 NF-κB p65）的水平。体外研究还证实了氢溶液的抗增殖能力以及 PDGF-BB 诱导的 VSMCs 中 ROS 的产生。