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非酒精性脂肪肝病與肝細(xì)胞癌關(guān)系的研究

發(fā)布時(shí)間:2019-05-30 09:37
【摘要】:目的 :研究非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)與肝細(xì)胞癌(hepatocellular carcinoma,HCC)的關(guān)系,并探討核因子κB(nuclear factor-κB,NF-κB)以及白細(xì)胞介素6(interleukin-6,IL-6)在致病機(jī)制中的作用。方法:將小鼠分為空白對(duì)照組、常規(guī)飲食組及高脂飲食組,從第16周起至36周對(duì)高脂飲食組及常規(guī)飲食組小鼠予以二乙基亞硝胺(diethylnitrosamine,DEN)45 mg/kg每周1次腹腔注射,誘導(dǎo)小鼠形成HCC,空白對(duì)照組不予任何藥物干預(yù);于第15、20、25和30周在常規(guī)飲食組及高脂飲食組中各取5只小鼠,空白對(duì)照組取3只小鼠,收集血清及肝組織;第36周處死所有小鼠,同樣收集小鼠血清及肝組織,并行HE染色分析肝組織形態(tài)學(xué)的變化,比較各組小鼠癌變率的差異,動(dòng)態(tài)監(jiān)測(cè)各組小鼠不同時(shí)期血清谷丙轉(zhuǎn)氨酶(alanine aminotransferase,ALT)、谷草轉(zhuǎn)氨酶(aspartate aminotransferase,AST)、甘油三酯(triglyceride,TG)和總膽固醇(total cholesterol,TC)的表達(dá)情況;ELISA法檢測(cè)血清中NF-κB和IL-6的含量。結(jié)果 :喂養(yǎng)15周后高脂飲食組小鼠成功建立NAFLD模型,空白對(duì)照組小鼠至第36周無自發(fā)成癌現(xiàn)象出現(xiàn)。常規(guī)飲食組小鼠誘癌成功率為40.0%(8/20),高脂飲食組小鼠誘癌成功率為83.3%(13/18)。各時(shí)期小鼠血清NF-κB和IL-6在高脂飲食組小鼠中的表達(dá)水平均明顯高于常規(guī)飲食組(P值均0.01)。結(jié)論 :NAFLD能促進(jìn)DEN對(duì)肝臟的致癌作用。炎性反應(yīng)因子NF-κB和IL-6作為促癌因子,其異常表達(dá)在NAFLD向HCC的進(jìn)展過程中發(fā)揮著重要的作用。
[Abstract]:Objective: to study the relationship between nonalcoholic fatty liver disease (non-alcoholic fatty liver disease,NAFLD) and hepatocellular carcinoma (hepatocellular carcinoma,HCC), and to explore the relationship between nuclear factor kappa B (nuclear factor- (NF-) and interleukin 6 (interleukin-6,). IL-6) plays an important role in pathogenesis. Methods: the mice were divided into blank control group, routine diet group and high-fat diet group. The mice in the high-fat diet group and the conventional diet group were given intraabdominal injection of diethylnitrosamine (diethylnitrosamine,DEN) 45 mg/kg once a week from the 16th week to the 36th week. The blank control group induced HCC, in mice was not interfered with any drugs. At the 15th, 20th, 25th and 30th week, 5 mice were taken in the routine diet group and 5 mice in the high fat diet group, and 3 mice in the blank control group were taken to collect serum and liver tissue. At the 36th week, all the mice were killed. The serum and liver tissue of the mice were also collected. The morphological changes of liver tissue were analyzed by HE staining. The difference of cancer rate in each group was compared. The serum glutamic-pyruvic transaminase (alanine aminotransferase, in different periods of each group was dynamically monitored. The expression of glutamic oxaloacetic transaminase (aspartate aminotransferase,AST), triglyceride (triglyceride,TG) and total cholesterol (total cholesterol,TC) in ALT),. The contents of NF- 魏 B and IL-6 in serum were detected by ELISA. Results: the NAFLD model was successfully established in the high fat diet group after 15 weeks of feeding, and no spontaneous carcinogenesis occurred in the blank control group at the 36th week. The success rate of cancer induction in conventional diet group was 40.0% (8 鈮,

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