小鼠非酒精性脂肪性肝炎中線粒體功能的障礙

創建日期:  2019/03/19  王婧   瀏覽次數:   返回

《上海大學學報(自然科學版)》2019年25卷1期:001-009

小鼠非酒精性脂肪性肝炎中線粒體功能的障礙
后文琳1, 潘雯1, 付思藝1, 宋美怡2, 王菲2
1. 上海大學 生命科學學院, 上海 200444; 2. 同濟大學附屬同濟醫院 消化內科, 上海 200065
摘要  [目的]研究非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)中線粒體功能的變化.[方法]C57BL/6小鼠采用膽堿蛋氨酸缺乏(methionine choline deficient,MCD)飲食誘導小鼠NASH模型,喂食膽堿蛋氨酸充足(methionine choline sufficient,MCS)組作為對照;4周后,處死小鼠同時取血清和肝組織.生化指標檢測血清丙氨酸氨基轉酶(alanineaminotransferase,ALT)活性、天冬氨酸氨基轉移酶(aspartate aminotransferase,AST)活性、肝組織甘油三酯(triglyceride,TG)、總膽固醇(total cholesterol,TC)水平;觀察肝組織病理學變化;實時熒光定量聚合酶鏈式反應(quantificational real-time polymerase chainreaction,qRT-PCR)檢測小鼠肝臟組織中mtDNA/nDNA和nDNA,以及由線粒體DNA編碼的的基因、線粒體DNA復制相關的基因、與小鼠肝臟中能量代謝相關的基因的表達變化.[結果]與MCS模型組相比,MCD組ALT,AST,TG水平明顯升高,但TC水平降低;肝組織變性嚴重,產生大量脂肪空泡,小葉結構破壞嚴重,炎細胞浸潤明顯;MCD模型組線粒體生成能力、能量代謝水平和DNA修復能力顯著降低.[結論]小鼠非酒精性脂肪性肝炎中線粒體功能發生障礙.
關鍵詞:   非酒精性脂肪性肝炎  線粒體  能量代謝

Dysfunction of mitochondrial in mice with non-alcoholic steatohepatitis
HOU Wenlin1, PAN Wen1, FU Siyi1, SONG Meiyi2, WANG Fei2
1. School of Life Sciences, Shanghai University, Shanghai 200444, China;
2. Department of Gastroenterology, Tongji Hospital Affiliated to Tongji University, Shanghai 200065, Chin

Abstract: [Objective] This research is to study the changes of mitochondrial function in non-alcoholic steatohepatitis (NASH).[Methods] The method is to use C57BL/6 mice fed with choline methionine deficient (MCD) diet to induce a mouse NASH model. The choline methionine sufficient (MCS) group serves as the control group. Four weeks later, serum and liver tissue are detected when mice are sacrificed. Biochemical indicators of serum alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, liver triglyceride (TG), total cholesterol (TC) levels are detected by enzymelinked immunosorbent assay. Pathological examination has also been performed. The mtDNA/nDNA and nDNA in liver tissue of mice and the expression of genes encoded by mitochondrial DNA, mitochondrial DNA replication and associated with energy metabolism in mouse liver are tested by qRT-PCR (quantificational real-time polymerase chain reaction).[Results] Compared with the MCS group, the MCD model group shows severe degeneration of liver tissue, and ALT, AST, and TG become significantly elevated, but TC levels are decreased. A large amount of fat vacuoles, severe destruction of lobular structure, and significant infiltration of inflammatory cells become increased in MCD model. In addition, the amount of mitochondrial is decreased. Furthermore, the capacity of energy metabolism and DNA repair of the MCD model group are significantly reduced.[Conclusion] Mitochondrial dysfunction occurs in mice with non-alcoholic steatohepatitis.
Key words:  non-alcoholic steatohepatitis (NASH)    mitochondria    energy metabolism

全文鏈接:http://www.journal.shu.edu.cn/fileup/1007-2861/PDF/20190101.pdf

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