Effects of treatment with hydrogen sulfide on methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats
Effects of treatment with hydrogen sulfide on methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats
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DOI：
10.1111/jgh.12389
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发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Tian, Fu-Zhou
中科院分区：
文献类型：
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作者：
Luo, Zhu-Lin;Tang, Li-Jun;Tian, Fu-Zhou
背景与目的氧化应激和炎症在单纯性脂肪肝向非酒精性脂肪性肝炎(NASH)的发展过程中起着重要作用。本研究旨在探讨硫化氢(H_2S)能否通过减轻氧化应激、抑制炎症反应来预防NASH的发生。实验分为3组：(1)对照组；(2)MCD饲料喂养大鼠；(3)NaHS处理组(每天腹腔注射硫化氢供体0.28mol/kg NaHS 0.1ml/kg/d)。苏木精-伊红染色显示，硫化氢可预防MCD饮食诱导的大鼠NASH，减少细胞凋亡，降低丙氨酸氨基转移酶和天冬氨酸氨基转移酶的活性，减轻肝脏脂肪堆积。H_2S通过减少细胞色素p4502E1的表达，增强血红素加氧酶-1的表达，抑制线粒体活性氧的形成，减轻MCD饮食诱导的氧化应激；通过抑制活化的核因子B信号，减少IL-6和肿瘤坏死因子的表达，抑制MCD饮食诱导的炎症反应。此外，硫化氢对MCD饮食大鼠肝脏脂肪酸代谢基因表达谱有有益的调节作用。结论硫化氢治疗可预防MCD饮食诱导的大鼠NASH，其机制可能与减轻氧化应激和抑制炎症有关。
Background and AimOxidative stress and inflammation play important roles in the progression from simple fatty liver to non-alcoholic steatohepatitis (NASH). The aim of this work was to investigate whether treatment with hydrogen sulfide (H2S) prevented NASH in rats through abating oxidative stress and suppressing inflammation.MethodsA methionine-choline-deficient (MCD) diet rat model was prepared. Rats were divided into three experimental groups and fed for 8 weeks as follows: (i) control rats; (ii) MCD-diet-fed rats; (iii) MCD-diet-fed rats treated with NaHS (intraperitoneal injection of 0.1mL/kg/day of 0.28mol/L NaHS, a donor of H2S).ResultsMCD diet impaired hepatic H2S biosynthesis in rats. Treatment with H2S prevented MCD-diet-induced NASH, as evidenced by hematoxylin and eosin staining, reduced apoptosis and activities of alanine aminotransferase and aspartate aminotransferase, and attenuated hepatic fat accumulation in rats. Treatment with H2S abated MCD-diet-induced oxidative stress through reducing cytochrome p4502E1 expression, enhancing heme oxygenase-1 expression, and suppressing mitochondrial reactive oxygen species formation, and suppressed MCD-diet-induced inflammation through suppressing activated nuclear factor B signaling and reducing interleukin-6 and tumor necrosis factor expressions. In addition, treatment of MCD-diet fed rats with H2S had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers.ConclusionsTreatment with H2S prevented NASH induced by MCD diet in rats possibly through abating oxidative stress and suppressing inflammation.