类风湿关节炎（Rheumatoidarthritis，RA）是一种以慢性侵蚀性关节炎为特征的全身性自身免疫病。类风湿关节炎的病变特点为滑膜炎，以及由此造成的关节软骨和骨质破坏，最终导致关节畸形。如果不经过正规治疗，约75%的患者在3年内出现残废。类风湿关节炎分布于世界各地，在不同人群中的患病为0.18%~1.07%，其发病具有一定的种族差异，印地安人高于白种人，白种人高于亚洲黄种人。在我国的总患病人数逾500万。类风湿关节炎在各年龄中皆可发病，高峰年龄在30~50岁左右，一般女性发病多于男性。类风湿关节炎的发病原因尚不明确，一般认为与遗传、环境、感染等因素密切相关。遗传因素类风湿关节炎患者1级亲属中患病的风险较普通人群高1.5倍。

   治疗类风湿关节炎的目标是控制系统性炎症不仅要控制症状，而且最好可改善患者基本健康状况。虽然使用针对促炎细胞因子的生物免疫抑制疗法获得了临床效果，但这类治疗手段仍无法避免副作用。由于类风湿关节炎的发病机制不明确，早期诊断和完全治疗仍无法实现。作为炎症相关疾病，活性氧在类风湿关节炎发病过程中具有重要作用，例如对炎症的关键信号核心分子NF-κB上游和下游传导通路都会产生重要影响。在各类活性氧中，羟基自由基是毒性最强的，氢气作为一种选择性抗氧化物质可特异性中和这类活性氧，这是目前学术界公认的氢气抗氧化抗炎症的分子基础。大量的临床和基础医学研究证明，氢气呼吸和氢气水对多种重要人类疾病具有理想或潜在的治疗作用，将可能对提高人类健康产生重大影响。最近，有学者证明使用氢气联合常规治疗方法可以显著减少类风湿关节炎患者的氧化应激损伤。特别是对早期患者，氢气显示出强大的治疗效果。

显然，自身免疫性疾病范围十分广泛，主要分为器官特异性自身免疫病和系统性自身免疫病。氢气对类风湿关节炎有效的临床研究给自身免疫性疾病的治疗提供了一个想像空间。考虑到氢气的极好的生物安全性，目前适合开展对这些疾病的临床治疗验证。

器官特异性自身免疫病，组织器官的病理损害和功能障碍仅限于抗体或致敏淋巴细胞所针对的某一器官。主要有慢性淋巴性甲状腺炎、甲状腺功能亢进、胰岛素依赖型糖尿病、重症肌无力、慢性溃疡性结肠炎、恶性贫血伴慢性萎缩性胃炎、肺出血肾炎综合征、寻常天皰疮、类天皰疮、原发性胆汁性肝硬变、多发性脑脊髓硬化症、急性特发性多神经炎等。

由于抗原抗体复合物广泛沉积于血管壁等原因导致全身多器官损害，称系统性自身疫病。习惯上又称之为胶原病或结缔组织病，这是由于免疫损伤导致血管壁及间质的纤维素样坏死性炎及随后产生多器官的胶原纤维增生所致。事实上无论从超微结构及生化代谢看，胶原纤维大多并无原发性改变，常见的自身免疫病有以下几种：①系统性红斑狼疮。②类风湿性关节炎。③系统性脉管炎。④硬皮病。⑤天疱疮。⑥皮肌炎。⑦混合结缔组织病。⑧自身免疫性溶血性贫血。⑨甲状腺自身免疫病。⑩溃疡性结肠炎。

New Antioxidant and Anti-inflammatory Therapy for Rheumatoid Arthritis and Relat.pdf

Curr Pharm Des 2013 Jul; Molecular Hydrogen: NewAntioxidant and Anti-inflammatory Therapy for Rheumatoid Arthritis and RelatedDiseases.

Ishibashi T

Haradoi Hospital, Department of Rheumatology andOrthopaedic Surgery, 6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan.toruishi@haradoi-hospital.com.

Rheumatoid arthritis (RA) is a chronic inflammatorydisease in which the progressive destruction of joint causes morbidity. It isalso associated with an increased risk of atherosclerosis, which can result incardiovascular disease and mortality. The therapeutic goal is to control thesystemic inflammation to obtain not only the remission of symptoms, but alsoimprove general state of health. Although recent biologic immunosuppressivetherapies targeting pro-inflammatory cytokines have spawned a paradigm shiftregarding the prognosis of RA, these therapies possess inherent side effects.Also, early diagnosis of the disease remains confounded by uncertainty. Whilethe mechanisms responsible for the onset of RA remain unclear, reactive oxygenspecies (ROS) play a significant role in the pathogenesis of RA. ROS play acentral role both upstream and downstream of NF-κB and TNFa pathways, which arelocated at the center of the inflammatory response. Among the ROS, the hydroxylradical is the most harmful, and molecular hydrogen (H2) is a selectivescavenger for this species. Recently, it has been shown that H2 is useful whenadministered along with the conventional therapy in RA as it acts to reduceoxidative stress in the patients. Especially in the early stage, H2 showedsignificant therapeutic potential, which also seemed to assist diagnosis andtreatment decisions of RA. The possible expectations regarding the potentialbenefits of H2 by reducing the oxidative stress, resulting from inflammatoryfactors, are raised and discussed here. They include prevention of RA andrelated atherosclerosis, as well as therapeutic validity for RA.