来自河北医科大学陈雅丽等的文章最近发表在INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE，文章题目为Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways

富氢生理盐水防疗颈动脉球囊损伤导致血管内膜增生。本研究目的是为了进一步分析这种现象的分子机制。富含氢气的生理盐水溶液（HRSS）大鼠每天注射，采用球囊损伤诱导的新内膜增生和新生内膜/介质比评估研究氢的效果。 HRSS显著减少新内膜面积和新内膜/介质比，该效应存在剂量依赖性。体外用胎牛血清（FBS）诱导血管平滑肌细胞（VSMC）增殖，观察氢的效应。富氢培养基（HRM）抑制大鼠血管平滑肌细胞增殖和迁移。 FBS诱导的活性氧（ROS）增加和激活细胞内Ras、MEK1 / 2、ERK1 / 2、增殖细胞核抗原（PCNA），Akt等，均受到HRM的抑制。HRM从G0/G1期阻断FBS的诱导细胞周期转化为S期，增加血管平滑肌细胞的凋亡率。这些结果表明，富氢的生理盐水是能够衰减FBS诱导的血管平滑肌细胞增殖和新内膜增生的抑制活性氧的产生和灭活Ras-ERK1/2-MEK1/2。

评语：这一研究非常有意思，过去大量研究证明氢对各类损伤引起的细胞碉亡具有阻断作用，但这一研究主要是抑制细胞增殖，促进细胞碉亡，如何理解这一“矛盾”的效应，非常值得深入思考。当然我们可以说这是两类不同性质的细胞碉亡，或者说细胞碉亡在损伤情况下是不利因素，但增生性疾病变成有利因素,因为碉亡可以对抗增生。但是,无论怎样，由于细胞碉亡存在类似细胞途径，为什么同一种物质对同一生物学效应产生完全相反的作用。难道氢只对机体表示友好？这显然不那么简单.过去我们一直认为氢气抗氧化无法转化成抗肿瘤效应，既然可以对抗组织增殖，而肿瘤显然也是一种增殖性疾病,也许氢气对肿瘤也存在类似促进碉亡的效应,1975年曾经有学者证明呼吸氢具有治疗皮肤鳞状细胞癌的作用,也许就是通过促进肿瘤细胞碉亡。本研究不足，尽管开展大量细胞学和分子水平的检测，但本研究仍没有摆脱描述性研究的局限，没有回答那些分子肯定在这一生物学效应中发挥作用。没有采用相反的处理手段，这是比较遗憾的问题。

Hydrogen-rich saline attenuates vascular smooth muscle cell
proliferation and neointimal hyperplasia by inhibiting
reactive oxygen species production and inactivating
the Ras-ERK1/2-MEK1/2 and Akt pathways
Yali Chen1, Jinyao Jiang2, Huibing Miao3, Xingjuan Chen4, Xuejun Sun5 and Yongjun Li2

1Department of Cardiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051;
2Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000;
Departments of 3Biochemistry and Molecular Biology, and 4Pharmacology, Institute of Basic Medicine,
Hebei Medical University, Shijiazhuang, Hebei 050011; 5Department of Diving Medicine, Faculty of
Naval Medicine, The Second Military Medical University, Shanghai 200433, P.R. China

Abstract. Hydrogen-rich saline has been reported to prevent neointimal hyperplasia induced by carotid balloon injury. The purpose of the present study was to further investigate the molecular mechanisms underlying this phenomenon. Daily injection of a hydrogen-rich saline solution (HRSS) in rats was employed to study the effect of hydrogen on balloon injury-induced neointimal hyperplasia and the neointima/ media ratio was assessed. HRSS significantly decreased the neointima area and neointima/media ratio in a dose-dependent manner. In vitro effects of hydrogen on fetal bovine serum (FBS)-induced vascular smooth muscle cell (VSMC) proliferation were also investigated. Hydrogen-rich medium (HRM) inhibited rat VSMC proliferation and migration induced by 10% FBS. FBS-induced reactive oxygen species (ROS) production and activation of intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), Akt were significantly inhibited by HRM. In addition, HRM blocked FBS-induced progression from the G0/G1 to the S-phase and increased the apoptosis rate of VSMCs. These results showed that hydrogen-rich saline was able to attenuate FBS-induced VSMC proliferation and neointimal hyperplasia by inhibiting ROS production and inactivating the Ras-ERK1/2-MEK1/2