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Study about the elucidation of hepatocarcinogenesis mechanism km fatty liver and preventive strategies based on pathogenic considerations

脂肪肝肝癌发生机制的阐明及基于病因的预防策略研究

基本信息

批准号：
18590574
负责人：
WATANABE Tetsu
金额：
$ 2.57万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590574/
关键词：
liver tumor fatty liver oxidative stress FLS mouse sodium butyrate NF-κB p21WAF

项目摘要

We used FLS mice (n=48) in this study. FLS mouse develops spontaneously fatty liver chronically without obesity. Liver tumors develop after age of 1 year. The FLS mice were subdivided into three groups : group 1 received control diet (CA-1) alone, group 2 received diet containing lactobacillus, and group 3 received control diet containing clostridium butyricum that produce butyric acid in a bowel after oral intake.At age 10 month, all mice showed significant fatty deposition in the liver without fibrosis. At age 12 month, 2 out of 8 mice in group 1 developed liver tumor, whereas 1 out of 8 mice developed liver tumor in both group 2 and 3. Measurement of short chain fatty acid in the feces by HPLC revealed that concentration of sodium butyrate increased in the mice of group 3.Immunohistochemical analysis of the liver of 10-month-old LPS mice showed that 4-HNE, a marker of oxidative stress, remarkably increased in group 1 mice compared with those in group 3 mice. On the contrary, the protein expression of transcription factor NF-KB increased in the liver of group 3 mice by the Western blot analysis. Phosphorylation of c-jun (Ser 73) was also observed in the liver of mice in group 3. Finally, protein expression of p21 WAF1 also increased in the liver of group 3 mice by the Western blot.These results indicate that oxidative stress takes a crucial role in the progression of liver disease in FLS mice. Oral intake of clostridium butyricum may protect the development of liver tumor in FLS mice.

我们在本研究中使用FLS小鼠（n=48）。FLS小鼠自发形成慢性脂肪肝，无肥胖。肝脏肿瘤在1岁以后发展。将FLS小鼠再分为3组：第1组仅接受对照饮食（CA-1），第2组接受含有丁酸的饮食，第3组接受含有丁酸梭菌的对照饮食，所述丁酸梭菌在口服摄入后在肠中产生丁酸。在12月龄时，第1组中8只小鼠中有2只发生肝肿瘤，而第2组和第3组中8只小鼠中有1只发生肝肿瘤。高效液相色谱法测定粪便中短链脂肪酸含量，结果显示第3组小鼠丁酸钠含量增加。免疫组化法检测10月龄LPS小鼠肝脏中氧化应激标志物4-HNE含量，结果显示第1组小鼠肝脏中氧化应激标志物4-HNE含量明显高于第3组。Western blot分析显示，第3组小鼠肝脏中转录因子NF-κ B的蛋白表达增加。在第3组小鼠的肝脏中也观察到c-jun（Ser 73）的磷酸化。最后，Western blot结果显示，第3组小鼠肝脏中p21 WAF 1蛋白表达增加，表明氧化应激在FLS小鼠肝脏疾病的进展中起着重要作用。口服丁酸梭菌对FLS小鼠肝癌的发生有保护作用。