非酒精性脂肪性肝炎大鼠肝脏内源性H2S合成减少

首都医科大学学报 ›› 2010, Vol. 31 ›› Issue (3): 287-292.

• 消化疾病发病机制和治疗的进展 • 上一篇下一篇

非酒精性脂肪性肝炎大鼠肝脏内源性H₂S合成减少

武彦宁¹, 蔡照华^3_,孙海梅², 尚宏伟², 郝刚², 张立新², 孙琳¹, 张华², 丁惠国^1*

1. 首都医科大学附属北京佑安医院肝病消化中心; 2. 首都医科大学基础医学院组织胚胎学教研室;3. 北京市第二医院消化科

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2010-06-21 发布日期:2010-06-21
通讯作者: 丁惠国

The Beneficial Role of Endogenous H₂S in Pathogenesis of Nonalcoholic Steatohepatitis Rats

WU Yan-ning¹, CAI Zhao-hua³, SUN Hai-mei², SHANG Hong-wei², HAO Gang², ZHANG Li-xin², SUN Lin¹, ZHANG Hua², DING Hui-guo^1*

1. Department of Hepatology and Gastroenterology, Beijing Youan Hospital, Capital Medical University; 2. Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University; 3. Department of Gastroenterology,The Second Hospital of Beijing Municipal

Received:1900-01-01 Revised:1900-01-01 Online:2010-06-21 Published:2010-06-21
Contact: DING Hui-guo

摘要/Abstract

摘要： 目的探讨非酒精性脂肪性肝炎（nonalcoholic steatohepatitis，NASH)大鼠肝脏硫化氢（hydrogen sulfide，H₂S）变化及与肝细胞线粒体损伤的可能关系。方法采用雄性SD大鼠26只，分为正常对照组（n=6）,NASH模型组（n=10）及复方牛胎肝提取物治疗组（n=10），高脂饮食12周建立NASH大鼠模型。亚甲基蓝分光光度法测定肝组织H₂S生成率，RT-PCR及免疫组织化学测定肝组织CSEmRNA及其表达。透射电子显微镜观察肝细胞超微结构、PCR法测定肝细胞线粒体DNA（mtDNA）片段ND₁、ND₆、CO₁、CYB及ATP₆。结果 NASH大鼠模型组肝细胞线粒体肿大、膜模糊或嵴消失，正常组大鼠mtDNA片段ND₁、ND₆、CO₁、CYB及ATP₆表达明显高于模型组和治疗组（P<0.05）。NASH模型组肝组织H₂S生成率〔（1.26±0.08）nmol/min〕较正常组〔（2.11±0.17）nmol/min〕明显减少（P<0.05），且肝脏CSEmRNA水平及其表达减少，治疗组与模型组比较差异无统计学意义。结论 NASH大鼠肝脏H₂S合成减少可能与肝细胞线粒体损伤有关，H₂S在NASH发病机制中可能具有保护肝脏的作用。

关键词: 非酒精性脂肪性肝炎, 线粒体DNA, 硫化氢, 胱硫醚-γ-裂解酶

Abstract:

Objective To investigate the production of H₂S and its protective role against mitochondrial dysfunction in rats with nonalcoholic steatohepatitis(NASH). Methods Twenty-six male Spague-Dawlay rats were randomly divided into 3 subgroups: normal group(n=6), NASH model(n=10), and compound fetal bovine liver extract treatment group(n=10). The NASH model was established by feeding rats with high fat diet for 12 weeks. The rate of production of H₂S was detected by methylene blue spectrophotometry and CSE mRNA was tested using RT-PCR. The mitochondrial morphology was assessed by transmission electron microscopy and the fragment of mtDNA, ND₁, ND₆, CO₁, CYB and ATP₆ were respectively tested by PCR. The hepatic steatosis and inflammation were evaluated using HE and Oil Red staining. Results In NASH rats, the hepatic tissue showed diffuse hepatic steatosis as lipid vacuolar degeneration with inflammatory cell infiltration, and the mitochondria showed swelling, becoming round, markedly abnormal morphology. The rate of liver production of H₂S in NASH rats was(1.26±0.08)nmol/min，which was significantly lower than that〔(2.11±0.17) nmol/min〕 in normal group(P<0.05). No significant difference in H₂S production between normal and treated group was observed. The decreased hepatic CSE mRNA and its protein were also observed. The level of mtDNA fragment, ND₁, ND₆, CO₁, CYB and ATP₆ in NASH rats were decreased. Conclusion The decreased hepatic H₂S production and CSE mRNA may be related to mitochondrial injury in NASH rats. Endogenous H₂S may play a beneficial role in pathogenesis of NASH.

Key words: nonalcoholic steatohepatitis, mitochondrial DNA, hydrogen sulfide, cystathioniniyase

中图分类号:

R 575.1

武彦宁;蔡照华_;孙海梅;尚宏伟;郝刚;张立新;孙琳;张华;丁惠国. 非酒精性脂肪性肝炎大鼠肝脏内源性H₂S合成减少[J]. 首都医科大学学报, 2010, 31(3): 287-292.

WU Yan-ning;CAI Zhao-hua;SUN Hai-mei;SHANG Hong-wei;HAO Gang;ZHANG Li-xin;SUN Lin;ZHANG Hua;DING Hui-guo . The Beneficial Role of Endogenous H₂S in Pathogenesis of Nonalcoholic Steatohepatitis Rats[J]. Journal of Capital Medical University, 2010, 31(3): 287-292.

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非酒精性脂肪性肝炎大鼠肝脏内源性H₂S合成减少

The Beneficial Role of Endogenous H₂S in Pathogenesis of Nonalcoholic Steatohepatitis Rats

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