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胆管阻塞可引起胆汁淤积,不仅对肝脏可造成严整损伤,引起肝脏急性损伤和纤维化,长期胆汁淤积可导致肝硬化和肝昏迷。而且由于可导致严重黄疸,容易引起全身性系统性症状。是肝胆外科长期关注的重点课题。胆管阻塞引起肝损伤的机制比较复杂,但氧化损伤是其中比较重要的环节。根据最近国内外发现氢气具有抗氧化作用,能治疗氧化应激性疾病。东方肝胆外科医院杨甲梅课题组,利用大鼠动物模型,首次在国际上证明,氢气生理盐水能通过提高肝脏抗氧化能力,抑制肝脏炎症反应,从而具有明显治疗胆管阻塞后肝损伤的作用。该研究扩展了氢气治疗疾病的研究范围,为氢气在肝硬化的临床应用奠定了重要基础。
氢气可选择性清除羟基自由基础,在许多氧化损伤动物模型中证明有治疗效果。氢气生理盐水是用氢气饱和的生理盐水,能提供高浓度的含氢气液体,使用安全方便,是一种比较理想的给氢气方式。本研究目的是证明氢气生理盐水是否能保护胆管阻塞引起的肝脏损伤。采用雄性SD大鼠,胆总管接扎后腹腔注射5或10ml/k g氢气生理盐水。结果发现,与对照组相比,胆总管接扎10天后,血清ALT 、AST,组织MDA含量和 MPO活性、TNF-α, IL-1β, IL-6,和HMGB1水平均明显升高。氢气生理盐水治疗组上述指标明显下降,肝脏组织学指标明显改善,同时肝脏抗氧化酶SOD和CAT活性明显升高,而ERK1/2明显下降。结果表明,氢气生理盐水对胆总管接扎后肝损伤具有明显治疗效果,其原因可能与氢气的抗氧化和抗炎症作用有密切关系。据悉,
Abstract: Background Hydrogen selectively reduces levels of hydroxyl radicals and alleviates acute oxidative stress in many models. Hydrogen-rich saline provides a high concentration of hydrogen that can be easily and safely applied. Aims In this study, we investigated the effects of hydrogen-rich saline on the prevention of liver injury induced by obstructive jaundice in rats. Methods Male Sprague–Dawley rats (n = 56) were divided randomly into four experimental groups: sham operated, bile duct ligation (BDL) plus saline treatment (5 ml/kg, i.p.), BDL plus low-dose hydrogen-rich saline treatment (5 ml/kg, i.p.), and BDL plus highdose hydrogen-rich saline treatment (10 ml/kg, i.p.). Results The liver damage was evaluated microscopically 10 days after BDL. Serum ALT and AST levels, tissue MDA content, MPO activity, TNF-α, IL-1β, IL-6, and HMGB1 levels were all increased significantly by BDL.Hydrogen-rich saline reduced levels of these markers and relieved morphological liver injury.Additionally, hydrogen-rich saline markedly increased the activities of antioxidant enzymes SOD and CAT and downregulated ERK1/2 activation. Conclusions Hydrogen-rich saline attenuates BDL-induced liver damage, possibly by reduction of inflammation and oxidative stress and inhibition of the ERK1/2 pathway.
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