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氫水對(duì)肝硬化的治療作用

東方肝膽外科醫(yī)院王紅陽院士課題組關(guān)于《氫氣治療肝臟損傷研究》,在國(guó)際著名雜志Journal of Hepatology發(fā)表。這是中國(guó)學(xué)者在氫氣生物學(xué)研究方面首次在10分以上雜志上發(fā)表論文。這說明我們?cè)跉浞肿俞t(yī)學(xué)研究領(lǐng)域的發(fā)展勢(shì)頭比較好,但是國(guó)際上發(fā)表相對(duì)好的論文數(shù)量超過中國(guó)學(xué)者,說明我們與國(guó)際同行仍存在明顯差距。

活性氧引起的氧化損傷是許多肝臟損傷的共同病理生理學(xué)過程,抗氧化能減少肝臟損傷,氫氣的選擇性抗氧化是最近的研究熱點(diǎn),但在肝臟損傷方面的研究仍不夠系統(tǒng)全面。本研究采用GalN/LPS, CCl4 DEN等三種肝損傷動(dòng)物模型,通過檢測(cè)氫氣、活性氧水平,評(píng)價(jià)氧化損傷、細(xì)胞碉亡和炎癥反應(yīng)程度,觀察氫氣生理鹽水在各類肝臟損傷的治療作用并探討其機(jī)制。研究結(jié)果發(fā)現(xiàn),氫氣生理鹽水對(duì)急性肝臟損傷、肝纖維化和肝臟細(xì)胞增生均具有顯著的抑制作用,同時(shí)細(xì)胞碉亡相關(guān)分子如JNK  caspase-3活性下降。研究結(jié)果證明氫氣不僅能治療急性肝臟損傷,而且能治療肝硬化。

07年日本學(xué)者證明動(dòng)物呼吸氫氣可治療肝臟缺血再灌注損傷,此后盡管在一些會(huì)議上日本曾報(bào)道過氫氣對(duì)脂肪肝治療方面的研究,但三年內(nèi)沒有任何其他關(guān)于氫氣與肝臟疾病方面的研究論文。這一研究說明中國(guó)學(xué)者在氫氣與肝臟疾病研究上領(lǐng)先于國(guó)際水平。該研究在氫氣生物學(xué)研究領(lǐng)域?qū)⒕哂幸欢ǖ牡匚唬陀^地講應(yīng)是中國(guó)學(xué)者唯一進(jìn)入第一梯隊(duì)研究。

不過,本研究更多是以依靠工作量取勝,最典型的是采用了三種類動(dòng)物模型,當(dāng)然對(duì)說明問題有幫助,但把這個(gè)研究放在國(guó)際氫氣治療疾病研究領(lǐng)域看,并沒有真正意義上突破目前國(guó)際上的研究水平,仍是從氧化損傷、炎癥和細(xì)胞碉亡這三個(gè)角度開展的研究。

論文全文 pdf pdf

The Protective Role of Hydrogen -Rich Saline in Experimental Liver Injury in Mice

HanYong Sunab, Lei Chena, Weiping Zhoub, Liang Hua, Liang Lia, QianQian Tuab, YanXin Changab, Qu Liub, XueJun Sund, MengChao Wub and HongYang Wangabc,

a International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China

b Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China

c National Laboratory for Oncogenes and Related Genes, Cancer Institute of Shanghai Jiao Tong University, Shanghai 200441, PR China

d Department of Diving Medicine, Second Military Medical University, Shanghai 200433, PR China

Received 8 January 2010;  

revised 18 August 2010;  

accepted 31 August 2010.  

Available online 25 September 2010.

Abstract

Background/Aims

Reactive oxygen species (ROS) are considered to play a prominent causative role in the development of various hepatic disorders. Antioxidants have been demonstrated effectively to protect against hepatic damage. Hydrogen (H2), a new antioxidant, was reported to selectively reduce the strongest oxidants, such as hydroxyl radicals (·OH) and peroxynitrite (ONOO-), and did not disturb metabolic oxidation-reduction reactions or disrupt ROS involved in cell signaling. In contrast to H2 gas,hydrogen-rich saline (HS) may be more suitable for clinical application. We here aim to verify its protective effects in experimental models of liver injury.

Methods

H2 concentration in vivo was detected by hydrogen microelectrode for the first time. Liver damage, ROS accumulation, cytokine levels and apoptotic protein expression were respectively evaluated after GalN/LPS, CCl4 and DEN challenge. Simultaneously, CCl4-induced hepatic cirrhosis and DEN-induced hepatocyte proliferation were measured.

Results

HS predominantly increased hydrogen concentration in liver and kidney tissues. Acute liver injury, hepatic cirrhosis and hepatocyte proliferation were reduced by quenching the detrimental ROS. Pro-apoptotic players such as JNK and caspase-3 activity were also inhibited.

Conclusions

HS could not only apparently protect against the liver injury but also inhibit the process of liver cirrhosis and hepatocyte compensatory proliferation.

Keywords: hydrogen-rich saline; acute hepatic failure; hepatic cirrhosis; hepatocyte proliferation; reactive oxygen species; inflammation; apoptosis; JNK

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