老年非酒精性脂肪肝的危险因素及增龄变化

目的评估老年人非酒精性脂肪肝(NAFLD)的危险因素及增龄变化。方法选择406例查体老年人,详细询问病史、查体,并行实验室化验检查及腹部彩超检查,对其结果进行统计学分析。结果查体老年人群中42.86%患有NAFLD,性别之间无明显差异(P0.05)。体重指数(BMI)、谷丙转氨酶(ALT)、尿酸(UA)及甘油三酯(TG)与NAFLD相关,但在60~74岁的人群中仅与BMI、空腹血糖(FPG)有关。NAFLD的患病率在60~70岁组、71~80岁组及81~92岁组,分别为43.59%、44.1%及41.8%,各组间无明显差异(P0.05)。结论 BMI、ALT、UA及TG为老年NAFLD的独立危险因素,需早期关注,在老年人中随着增龄,NAFLD的患病率无明显变化。     

酒精性脂肪肝大鼠肝组织骨桥蛋白表达的变化

目的探讨乙醇联合高脂饮食诱导脂肪肝大鼠肝组织骨桥蛋白（OPN）表达的变化。方法采用高脂饮食联合乙醇灌胃制备大鼠脂肪肝模型。在第6周末分别取血和肝组织,常规检测血生化指标和采用Westernblot法检测大鼠肝组织骨桥蛋白表达的改变。结果乙醇联合高脂饮食条件下大鼠血清ALT、AST、TG、TC水平升高（P〈0．05）,HDL-C降低（P〈0．05）;油红O染色结果显示乙醇联合高脂饮食组大鼠肝脏脂肪变明显;模型组大鼠肝组织OPN蛋白表达明显增强（P〈0．05）。结论骨桥蛋白表达增强在大鼠乙醇性脂肪肝的发病过程中起一定的作用。     

非酒精性脂肪肝病

第十二届世界消化病学会议于 2 0 0 2年 2月在泰国曼谷召开 ,这是继 1998年第十一届世界消化病学术会议(奥地利维也纳 )之后的又一次“奥林匹克式”的国际盛会 ,百余个国家的万余名医师出席了这次大会。会议内容广泛 ,涉及到多方面的新进展。《临床消化病杂志》曾相继及时报道了 1994年第十届及 1998年第十一届世界消化病学术大会的部分专题内容 ,受到广大读者欢迎。本期我们又组织华中科技大学同济医学院协和医院消化科医师整理了第十二届世界消化病学会大会上所涉及的近 4年来国际上在消化疾病某些领域中的最新进展 ,供同道们参考。     

非酒精性脂肪肝的流行病学

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)俗称脂肪肝,是指以肝实质细胞脂肪变性为病理特征,而无过量饮酒史,又除外其他肝病的临床综合征,其病理类型包括单纯性脂肪肝、脂肪性肝炎(NASH)及NASH相关肝硬化,后者可发展为肝癌[1-3].NAFLD常与肥胖、2型糖尿病、血脂紊乱、高血压等代谢综合征(MS)症状并存,近年患病率呈逐年增加的趋势,已成为慢性肝病及血清氨基酸转移酶(下称转氨酶)水平升高的主要原因之一.     

非酒精性脂肪肝的影像学诊断

随着我国社会经济的不断发展,人们的饮食习惯及饮食结构也发生了明显变化,非酒精性脂肪肝（Nonalcoholic Fatty Liver Disease,NAFLD）的患病率逐年增长,加强对NAFLD发病机理和防治方法的研究已经成为医学领域一个非常迫切的问题。NAFLD的发生主要与胰岛素抵抗有关,其主要原因是肝内脂肪合成与极低密度脂蛋白分泌之间的平衡失调。     

Liver structural transformation after partial hepatectomy and repeated partial hepatectomy in rats: A renewed view on liver regeneration

BACKGROUND The phenomenon of liver regeneration after partial hepatectomy(PH) is still a subject of considerable interest due to the increasing frequency of half liver transplantation on the one hand, and on the other hand, new surgical approaches which allow removal of massive space-occupying hepatic tumors, which earlier was considered as inoperable. Interestingly, the mechanisms of liver regeneration are extensively studied after PH but less attention is paid to the architectonics of the regenerated organ. Because of this, the question "How does the structure of regenerated liver differ from normal, regular liver?" has not been fully answered yet. Furthermore, almost without any attention is left the liver's structural transformation after repeated hepatectomy(of the re-regenereted liver).To compare the architectonics of the lobules and circulatory bed of normal, regenerated and re-regenerated livers.METHODS The livers of 40 adult, male, albino Wistar rats were studied. 14 rats were subjected to PH-the 1st study group(SG_1); 10 rats underwent repeated PH – the 2nd study group(SG2); 16 rats were subjected to sham operation-control group(CG); The livers were studied after 9 months from PH, and after 6 months from repeated PH. Cytological(Schiff reaction for the determination of DNA concentration), histological(HE, Masson trichrome, CK8 Immunohistochemical marker, transparent slides after Indian Ink injection,), morphometrical(hepatocytes areas, perimeters and ploidy) and Electron Microscopical(Scanning Electron Microscopy of corrosion casts) methods were used.RESULTS In the SG_1 and SG_2, the area of hepatocytes and their perimeter are increased compared to the CG(P 0.05). However, the areas and perimeters of the hepatocytes of the SG_1 and SG_2 groups reveal a lesser difference. In regenerated(SG_1) and re-regenerated(SG_2) livers, the hepatocytes form the remodeled lobules, which size(300-1200 μm) exceeds the sizes of the lobules from CG(300-600 μm). The remodeled lobules(especially the "mega-lobules" with the sizes 1000-1200 μm) contain the transformed meshworks of the sinusoids, the part of which is dilated asymmetrically. This meshwork might have originated from the several portal venules(interlobular and/or inlet). The boundaries between the adjacent lobules(including mega-lobules) are widened and filled by connective tissue fibers, which gives the liver parenchyma a nodular look. In SG_2 the unevenness of sinusoid diameters, as well as the boundaries between the lobules(including the mega-lobules) are more vividly expressed in comparison with SG_1. The liver tissue of both SG_1 and SG_2 is featured by the slightly expressed ductular reaction.CONCLUSION Regenerated and re-regenerated livers in comparison with normal liver contain hypertrophied hepatocytes with increased ploidy which together with transformed sinusoidal and biliary meshworks form the remodeled lobulli.     

普罗布考对大鼠非酒精性脂肪性肝病的预防及机制研究

目的 观察普罗布考对大鼠非酒精性脂肪性肝病（NAFLD）的预防作用．并探讨其可能作用机理。方法 24只雄性sD大鼠随机分3组：正常对照组、NAFLD对照组、普罗布考干预组。以高脂饲料饲养诱发脂肪肝大鼠模型。18周末，处死所有动物，检测血脂、肝功能、肝脂质含量、氧化还原指标、肝组织病理学等。结果与NAFLD对照组比较，普罗布考干预组TC（2．98±0．90）mmol／L vs（4．45±1．15）mmol／L，ALT（78．25±18．47）U／L vs（110．2±36．33）U／L及肝组织TG含量（2．61±0．20）mmol／L vs（2．93±0．36）mmol／L均显著下降（P均〈0．05），其肝脂肪变性及炎症程度亦显著减轻（P均〈0．05）。结论 普罗布考可对高脂饲料饲养诱发的大鼠NAFLD产生保护作用；其保护作用与提高机体抗氧化能力．减轻组织氧化应激损害有关。     

Multivariate analysis of liver regenerative capacity after hepatectomy in humans

Many factors affect liver regeneration after partial hepatectomy; however, those factors that are essential for regulation of liver regeneration in humans are not known. Using multiple regression analysis we conducted a study to determine essential factors involved in the speed of liver regeneration after hepatectomy. The subjects were 59 patients who underwent hepatic resection between January 1980 and December 1991. A regression equation for predicting regeneration speed (Y; cm³/day) during the 1st postoperative month was obtained by stepwise forward multiple regression analysis, using 11 explanatory parameters (Xi). The regeneration speed and the resection ratio (%; indicating the magnitude of resection) were calculated based on a computed tomography (CT) scan volumetric study. The degree of liver fibrosis, expressed as the fibrotic index (%), was morphometrically determined in Azan-Mallory stained sections. Of the 11 explanatory parameters, the resection ratio and the fibrotic index had a significant simple correlation with Y. The following regression equation was obtained: Y (cm³/day)=?1.1+3.7 × resection ratio ?5.4 × alkaline phosphatase ?3.7 × fibrotic index +1.2 × total bilirubin ?2.6 × glutamic pyruvic transaminase (multiple correlation coefficient, 0.82). We found that the extent of resection and the degree of fibrosis, as well as alkaline phosphatase, total bilirubin, and glutamic pyruvic transaminase, contributed to the speed of regeneration after partial hepatectomy.     

大鼠非酒精性脂肪性肝纤维化形成过程中骨桥蛋白的表达及其意义

目的 通过观察非酒精性脂肪性肝纤维化形成过程中肝组织内骨桥蛋白(OPN)的变化规律,探讨OPN在非酒精性脂肪性肝纤维化形成过程中的作用. 方法选用纯系Wistar雄性大鼠56只,体质量180～200g,随机分为正常对照组和高脂饮食4、8、12,16、20、24周组(其中每组各8只).肝组织常规进行HE及Masson三色胶原染色,免疫组织化学染色检测肝组织α-平滑肌肌动蛋白的表达,RT-PeR、Western blot观察肝组织中OPN动态变化.结果 与正常对照组相比,高脂饲料组大鼠肝脏内OPN含量明显升高,随着脂肪肝程度的加重,OPN表达逐渐增强,mRNA及蛋白质表达比较,F值分别为7.30和7.15,尸值均<0.01;与α-平滑肌肌动蛋白表达及肝组织胶原纤维面积百分比呈显著正相关(r值分别为0.94和0.82,P值均<0.01).结论 在非酒精性脂肪性肝纤维化形成过程中,OPN在肝组织中表达显著上调,可能在非酒精性脂肪性肝纤维化的形成过程中发挥重要作用.     

生长激素对鼠部分肝切除术后肝再生影响

目的　探讨生长激素对 70 %肝切除后肝再生的影响。方法　 60只SD大鼠随机分为对照组及生长激素组 ,按Higgins方法行 70 %肝切除术 ,术后给药并分批于术后 6、2 4、48、72、96h处死 ,作如下比较 :①残肝肝重 ;②增殖细胞核抗原 (PCNA)标记指数 ;③图像定量分析法测量PCNA阳性产物面积及灰度值。结果　与对照组比较 ,生长激素组残肝肝重、PCNA标记指数、PCNA阳性产物面积在术后均显著增高 (P <0 .0 5 ) ,而灰度值则显著降低 (P <0 .0 5 )。结论　生长激素具有强烈促进肝细胞增殖和刺激肝再生的作用     

脂联素及其在非酒精性脂肪性肝病中的作用研究进展

非酒精性脂肪性肝病(NAFLD)已成为危害人类健康的主要消化道疾病之一,及早发现和治疗NAFLD已引起广泛的关注。对于NAFLD的发病机制至今仍存在争议,但与代谢综合征(中心性肥胖、高甘油三酯血症、低高密度脂蛋白胆固醇血症、口服葡萄糖耐量试验异常和高血压等)具有一定的相关性,而脂联素在代谢综合征的发生、发展过程中起着重要的     

5-羟色胺2A受体阻断剂对大鼠肝脏再生的影响

目的观察5-羟色胺2A受体阻断剂酮色林对大鼠肝部分切除后肝再生的影响,了解5-羟色胺及其受体在肝脏再生中的作用。方法 80只雄性Wistar大鼠随机分为实验组和对照组。采用肝大部分切除术建立肝再生模型,术后16 h分别给予腹腔内注射酮色林（实验组）和生理盐水（对照组）,采用免疫组化及流式细胞技术动态观察并比较两组大鼠术后24、36、48、72 h肝脏Ki67、增殖细胞核抗原的表达情况。结果大鼠肝大部切除术后24、36 h肝脏表达Ki67、增殖细胞核抗原最为活跃,而后表达逐渐下降。实验组大鼠肝脏表达Ki67、增殖细胞核抗原较对照组显著下降（P〈0.05）。结论 5-羟色胺2A受体阻断剂酮色林显著抑制大鼠肝大部切除术后的肝脏再生,说明5-羟色胺具有一定的促进肝再生的作用,2A受体是其重要的信号传导受体之一。     

Endothelial autophagy is not required for liver regeneration after partial hepatectomy in mice with fatty liver

Background & Aims

Patients with non-alcoholic fatty liver disease (NAFLD) have impaired liver regeneration. Liver endothelial cells play a key role in liver regeneration. In non-alcoholic steatohepatitis (NASH), liver endothelial cells display a defect in autophagy, contributing to NASH progression. We aimed to determine the role of endothelial autophagy in liver regeneration following liver resection in NAFLD.

Methods

First, we assessed autophagy in primary endothelial cells from wild type mice fed a high fat diet and subjected to partial hepatectomy. Then, we assessed liver regeneration after partial hepatectomy in mice deficient (Atg5^lox/lox;VE-cadherin-Cre⁺) or not (Atg5^lox/lox) in endothelial autophagy and fed a high fat diet. The role of endothelial autophagy in liver regeneration was also assessed in ApoE^−/− hypercholesterolemic mice and in mice with NASH induced by methionine- and choline-deficient diet.

Results

First, autophagy (LC3II/protein) was strongly increased in liver endothelial cells following hepatectomy. Then, we observed at 40 and 48 h and at 7 days after partial hepatectomy, that Atg5^lox/lox;VE-cadherin-Cre⁺ mice fed a high fat diet had similar liver weight, plasma AST, ALT and albumin concentration, and liver protein expression of proliferation (PCNA), cell-cycle (Cyclin D1, BrdU incorporation, phospho-Histone H3) and apoptosis markers (cleaved Caspase-3) as Atg5^lox/lox mice fed a high fat diet. Same results were obtained in ApoE^−/− and methionine- and choline-deficient diet fed mice, 40 h after hepatectomy.

Conclusion

These results demonstrate that the defect in endothelial autophagy occurring in NASH does not account for the impaired liver regeneration occurring in this setting.