消瘀化痰方对非酒精性脂肪肝大鼠肝脏解偶联蛋白2 mRNA表达的影响

目的 观察消瘀化痰方对非酒精性脂肪肝(NAFLD)大鼠肝脏解偶联蛋白2 mRNA(UCP2 mRNA)表达的影响,探讨其防治NAFLD的部分作用机制.方法采用喂饲高脂饲料的方法复制NAFLD大鼠模型,实验分为正常对照组、模型组、东宝肝泰对照组和消瘀化痰方高、低剂量组.提取肝脏总RNA,运用半定量RT-PCR技术观察各组大鼠肝脏UCP2 mRNA的表达情况,同时测定各组大鼠血清总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)和肝组织匀浆TC、TG的含量,并做病理组织切片.结果模型组大鼠UCP2 mRNA的表达增强,血脂和肝脏脂质含量明显升高,肝脏呈明显脂肪变性.经药物治疗后,各治疗组大鼠肝脏UCP2 mRNA的表达减弱,血脂和肝脏脂质含量显著降低,肝脂变程度明显减轻.结论消瘀化痰方通过调控NAFLD大鼠肝脏UCP2 mRNA的适度表达,可能是其治疗NAFLD的分子机制之一.     

大鼠非酒精性脂肪肝中UCP2的动态表达

目的探讨解偶联蛋-2(uncoupling protein-2,UCP2)在大鼠非酒精性脂肪肝发病机理中的作用.方法Wistar大鼠64只,随机分为高脂饮食诱导脂肪肝组和正常对照组,用免疫组织化学和Western blot技术检测肝组织中UCP2表达变化,生化检测大鼠血清甘油三酯(TG)、游离脂肪酸(FAA)和丙氨酸氨基转移酶(ALT)含量.结果大鼠非酒精性脂肪形成过程中UCP2阳性细胞数和表达强度逐渐增加,血清TG、FAA和ALT含量较对照组增高,以高脂饮食喂养8、12周为著.结论随着非酒精性脂肪的形成和程度加重,UCP2表达逐渐增强,其介导的酶活性显著增高,启动脂质过氧化反应,促进脂肪肝的形成和发展.     

2型糖尿病并脂肪肝大鼠肝脏解偶联蛋白2表达及罗格列酮的干预作用

解偶联蛋白2（UCP2）是线粒体内膜上具有调节质子跨膜转运作用的阴离子转运蛋白。这种介导质子的跨膜内流,在调节能量代谢、脂肪酸的B氧化等均有重要作用。2型糖尿病（T2DM）患者中非酒精性脂肪性肝病（NAFLD）的发生率高达50％以上,脂肪肝患者UCP2的表达是一把“双刃剑”,对NAFLD的发生及预后起着至关重要的作用。本研究通过高脂饲养加小剂量STZ制成T2DM并NAFLD大鼠模型．观察各组间大鼠肝脏UCP2蛋白和mRNA表达,并探讨罗格列酮对脂肪肝的于预效果及可能的作用机制。     

己酮可可碱对非酒精性脂肪肝大鼠肝组织线粒体解耦联蛋白表达的影响

目的 探讨己酮可可碱(PTX)对非酒精性脂肪肝性肝病(NAFLD)大鼠线粒体解耦联蛋白(UCP)-2 mRNA表达的影响. 方法 SD大鼠60只,正常喂养1周后随机分为3组,每组20只.其中对照组20只,以普通饲料喂养,实验组和干预组各20只,以高脂饲料喂养,干预组高脂饮食4周后,在饮水中加用已酮可可碱(PTX)(100 mg·Kg-1·d-1),于第24周处死,采用反转录聚合酶链反应(RT-PCR)技术检测肝脏UCP-2mRNA的表达. 结果 对照组大鼠肝脏UCP2mRNA呈微量表达(1.2±0.1),实验组大鼠肝脏UCP2mRNA呈强表达(4.0±0.3),干预组大鼠肝脏UCP2mRNA呈弱表达(3.0±0.2),3组间UCP-2mRNA表达差异有统计学意义(F=160.67,P＜0.01). 结论 己酮可可碱可下调NAFLD大鼠肝细胞UCP-2mRNA的表达.     

虫草菌丝对实验性大鼠非酒精性脂肪肝解偶联蛋白2的影响

解偶联蛋白2(UCP2)一方面可以防止非酒精性脂肪肝(NAFLD)发生，另一方面，可能对机体造成不良后果。本实验观察了虫草菌丝对UCP2在脂肪肝形成过程中表达的影响。     

替度鲁肽对大鼠非酒精性脂肪性肝病的治疗作用

目的:探讨GLP-2类似物替度鲁肽治疗大鼠非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的作用.方法:30只SD大鼠随机分为正常饮食组和高脂饮食组,至第12周末时两组分别取6只大鼠判断NAFLD造模成功与否.第13周起,以剩余正常饮食组大鼠为对照(n=6),高脂饮食组随机分为NAFLD组(n=6)和GLP-2组(n=6),其中GLP-2组注射替度鲁肽液,对照组和NAFLD组注射生理盐水,7 d后眼眶取血并处死取材,检测NAFLD相关生化指标和病理观察.结果:NAFLD模型成功构建,高脂饮食组肝脏匀浆的总甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)及肝脏活动度积分(NAFLD activity score,NAS)均高于正常饮食组(P0.05);且高脂饮食组十二指肠肠道黏膜上皮细胞排列疏松、间隙变大,黏膜Claudin-2蛋白表达增多(P0.05).给药G L P-2后,肝脏匀浆的T G、T C及肝脏N A S均低于NAFLD组(P0.05);且改善了肠道黏膜上皮细胞的排列,减小了细胞间隙和黏膜Claudin-2蛋白的表达(P0.05).结论:NAFLD发病可导致肠道黏膜细胞间隙增大,Claudin-2蛋白表达升高,替度鲁肽可能通过降低NAFLD大鼠肠道黏膜Claudin-2蛋白的表达,从而改善NAFLD的肝脏病变.     

非酒精性脂肪性肝病大鼠肝脏解偶联蛋白2表达及其与能量贮备的关系

目的探讨非酒精性脂肪性肝病(NAFLD)大鼠肝脏线粒体解偶联蛋白2(UCP2)表达及其与能量贮备的关系。方法模型组SD大鼠给予高脂肪高胆固醇饮食饲养,分批于实验第8、12、16、24 周处死,同期设普通饮食饲养大鼠作对照。免疫组织化学和逆转录聚合酶链反应(RT-PCR)检测肝脏UCP2 mRNA转录及其蛋白表达。荧光测定法检测肝脏三磷酸腺苷(ATP)含量。结果模型组大鼠8周呈现单纯性脂肪肝,12-24周从脂肪性肝炎进展为脂肪性肝炎伴肝纤维化。免疫组织化学和RT-PCR显示,随着造模时间延长,模型组肝脏UCP2表达逐渐增强,UCP mRNA转录于24周达高峰,较对照组升高4.2倍, t=16.474,P<0.01;模型组肝脏ATP含量则随造模时间延长而逐渐减低,24周为(1.99±0.66) ×108μmol/g,对照组为(2.97±0.48)×108μmol/g,t=3.248,P<0.01。模型组肝脏UCP2 mRNA 转录的相对数值与其ATP含量呈密切负相关,r=-0.93,P<0.01。结论持续24周高脂饮食成功复制大鼠NAFLD模型,模型大鼠肝脏UCP2表达增强而ATP含量减少,两者之间关系密切。     

肝细胞色素P450 2E1在大鼠非酒精性脂肪肝形成中的作用

目的 研究肝细胞色素P450 2E1在大鼠非酒精性脂肪肝形成中的作用。方法 Wistar大鼠40只，随机分为正常对照组和高脂饲料2、4、8和12周组(其中每组各8只)：HE染色光镜观察肝脏组织病理改变；硫代巴比妥酸法测定肝脏组织丙二醛(MDA)的含量变化：免疫组织化学和Westemblot方法研究高脂饲料诱导的大鼠脂肪肝形成中肝细胞色素P450 2E1表达变化。结果 高脂饲料组大鼠肝脏内MDA含量明显高于对照组，随时间延长，逐渐增加：随着脂肪肝程度的加重，MDA含量逐渐增强，肝细胞色素P450 2E1蛋白表达亦明显增强。结论 非酒精性脂肪肝大鼠肝细胞色素P450 2E1表达变化与脂肪肝引起的脂质过氧化损伤程度密切相关。     

黄芪注射液对糖尿病非酒精性脂肪肝模型大鼠血糖、血脂及肝脏脂肪分化相关蛋白表达水平的影响

目的研究黄芪注射液对糖尿病非酒精性脂肪肝模型大鼠血糖、血脂及肝脏脂肪分化相关蛋白表达水平的影响。方法采用高糖高脂结合链脲佐菌素诱导Wistar大鼠糖尿病非酒精性脂肪肝模型;将大鼠随机分为对照组、模型组及黄芪注射液干预组,分别于实验8周、12周及16周检测大鼠血清血糖、三酰甘油（TG）、总胆固醇（TC）的表达水平;HE切片观察大鼠肝脏病理形态的改变;免疫印迹（western—blot）检测大鼠肝脏脂肪分化相关蛋白（ADRP）的表达水平。结果高糖高脂结合链脲佐菌素大鼠血糖、TG、TC增高,肝脏脂肪发生变性,糖尿病非酒精性脂肪肝模型构建成功。实验12周,干预组大鼠血清血糖、TG、TC水平均低于模型组,但差异无统计学意义（P〉0．05）,肝脏脂肪变性程度与模型组大鼠基本相当,炎细胞浸润程度较模型组程度轻;实验16周,干预组大鼠血清血糖及TG水平明显低于模型组,差异有统计学意义（P〈0．05）,肝脂肪变性程度较模型组明显减轻,炎细胞浸润基本消失;与正常对照组相比,NAFLD大鼠肝脏ADRP水平显著增高（P〈0．05）,通过黄芪注射液治疗后,NAFLD模型肝脏ADRP的表达水平下调。结论黄芪注射液可改善NAFLD大鼠血糖血脂代谢紊乱,减轻肝脏的炎症反应和变性,具有一定的肝脏保护作用。     

T辅助细胞亚群在大鼠非酒精性脂肪性肝病模型中的变化

目的:探讨T辅助细胞亚群Th1/Th2和Treg在非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)发病机制中的意义.方法:SD大鼠正常喂养1 wk后,随机分为正常组(n=20)和高脂饮食组(n=20).正常组大鼠以普通饲料喂养,高脂饮食组以高脂饲料喂养.实验第8、16周分批处死大鼠.观察肝组织的病理改变.荧光定量PCR方法检测肝脏TNF-α、IFN-γ、IL-4和Foxp3的基因表达.结果:高脂饮食8 wk大鼠肝细胞脂肪变明显,无明显炎症改变,IFN-γ、IL-4在肝脏的基因表达与正常组比较无明显变化,TNF-α稍升高,但无统计学意义,Foxp3 mRNA的表达比正常组明显降低(ct值:26.12±0.69 VS 24.22±0.62,P<0.05).高脂饮食16 wk大鼠脂肪肝明显,炎症明显,IFN-γ和TNF-α基因表达均显著升高(ct值:24.52±0.87 vs 29.94±1.44,24.31±1.13vs28.88±1.95,均P<0.05),IL-4与正常组相比较无明显变化,Foxp3基因表达较正常组和高脂饮食8 wk时均显著降低(ct值:32.57±1.54 vs 24.29±1.08,26.12±0.69,P<0.05).结论:高脂饮食大鼠肝脏Foxp3和Treg表达减少可能是高脂饮食NAFLD发生发展的重要因素.IFN-γ和TNF-α的联合作用加重了肝脏的炎症损伤.     

Results of liver resection for primary liver cancer

At the Zhong Shan Hospital, Shanghai Medical University, between 1960 and 1991, liver resection was performed in 896 patients with primary liver cancer; local resection was performed in 552 patients (61.6%), left lateral segmentectomy in 114 (12.7%), left hemihepatectomy in 157 (17.5%), extended left hemihepatectomy in 19 (2.1%), right hemihepatectomy in 50 (5.6%), and extended right hemihepatectomy in 4 (0.4%). The overall operative mortality was 4.6%, but it was 22.0% in 1960–1970, 7.0% in 1971–1980, and 2.8% in 1981–1991. Encouraging changes in the prognostic pattern were observed when comparing the data for 1960–1970 (n=59), 1971–1980 (n=115), and 1981–1991 (n=722): the 5-year survival rate was 14.0%, 36.0%, and 50.8%, respectively, and the 10-year survival rate was 12.3%, 25.5%, and 40.8%, respectively. Significant differences in survival patterns were noted when these were analyzed on the basis of tumor size (≤5 vs >5cm), curative resection, tumor number, tumor capsule, and tumor emboli in the portal vein. In the entire series, 135 patients have survived for more than 5 years after resection, and 40 patients for more than 10 years after resection. One patient has survived for 32 years and is still alive, free of disease. The approaches to decreasing operative mortality and prolonging survival rate are discussed.     

Implication of normal liver enzymes in liver disease

Summary.  Chronic liver disease is usually asymptomatic until its late stages and also significant hepatic necroinflammation and fibrosis may be present in persistently normal ALT levels HBV, HCV carriers or similarly, in patients with nonalcoholic fatty liver disease. Given the large number of persons in the general population which may harbor a clinically significant liver disease behind the screen of normal alanine aminotransferase, more attention should be devoted to future research for alternative noninvasive markers of liver damage.     

Recurrence of autoimmune liver diseases after liver transplantation

Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.     

Life support of artificial liver: development of a bioartificial liver to treat liver failure

In recent years there has been a particular focus on research regarding tissue engineering targeting the liver, especially in terms of what types of cells and extracellular matrices should be organized and in what type of environments to create an artificial liver, i.e., a life-saving organ. The ideal is to use healthy human liver cells as a source of cells for such research, but there is an extreme shortage of human-donor livers that can be used for cell isolation. Therefore, we are presently working on the differentiation of embryonic stem cells into liver cells as well as reversibly immortalized human liver cell lines that can be cultured in large quantities and at low cost. We are also working on the development of a bioartificial liver (BAL) using such cells as a source. Herein, we introduce our findings on the current status of BAL development.     

Pulmonary aspects of liver disease and liver transplantation

This article has summarized the liver-lung relationships from a clinical perspective. The physiology, biochemistry, and molecular biology that link the two organs are of great importance in that many disorders described affect young patients. Indeed, pulmonary abnormalities in patients with hepatic disorders are frequent, and both the pulmonary and hepatic problems may be reversible in the current era of organ transplantation.