肝脏萎缩增生复合征萎缩肝组织病理和功能分化的临床研究

发布时间：2018-05-01 02:07

本文选题：萎缩-增生复合征 + 病理学　；参考：《中国人民解放军医学院》2014年博士论文

【摘要】：背景肝萎缩-增生复合征（the atrophy-hypertrophy complex，AHC）是由于门静脉、肝静脉或胆管的梗阻，导致梗阻支配区域的肝组织萎缩和健侧肝组织的代偿性增生。肝内胆管结石和肝门部胆管癌常引起AHC。部分复杂的肝内胆管结石常因残余肝太少而无法手术切除，病变的萎缩肝组织对维持正常肝功能可能具有重要意义。对于肝门部胆管癌等需要行扩大半肝切除的病人术前行门静脉栓塞（Portal vein embolization，，PVE），使患侧肝萎缩和健侧肝代偿性增生，在此代偿过程中，萎缩肝组织对机体维持正常肝功能也可能起着重要作用。肝腺泡是肝脏的结构和功能的基本单位，具有功能分化特征。目前对AHC萎缩肝组织的病理和功能特征的研究极少。本课题拟选取AHC术后萎缩和增生肝组织行自身对照研究，探讨AHC萎缩肝组织的病理变化和功能特征。方法在解放军总医院三0四临床部伦理委员会的批准下和患者的知情同意下，选取2008年1月至2013年12月AHC病例28例，包括肝内胆管结石24例和肝门部胆管癌4例。在肝部分切除后将萎缩和增生肝组织行自身对照研究，观察萎缩肝组织的大体形态改变，并在光镜下观察萎缩肝组织的病理改变，在扫描电镜下观察萎缩组织肝细胞超微结构变化；选取肝组织中与营养代谢和解毒功能有关的白蛋白（albumin， ALB）、与糖酵解有关的磷酸丙糖异构酶（triosephosphate isomerase, TPI）和甘油醛-3-磷酸脱氢酶（glyceraldehyde-3-phosphate dehydrogenase，GAPDH）、与有氧氧化和糖异生有关的磷酸烯醇丙酮酸羧激酶（phosphoenolpyruvate carboxykinase,PEPCK）、与胆固醇代谢有关的载脂蛋白A-1（apolipoprotein A-1，Apo A-1）、与氨基酸代谢有关的谷氨酸脱氢酶（glutamate dehydrogenase，GDH）、与脂肪酸代谢和色素形成有关的肝脏脂肪酸结合蛋白（liver fatty acid bindingprotein，L-FABP）以及与生物转化和胆红素运输有关的谷胱甘肽转移酶（glutathione S-transferase, GST）作为观察指标，利用免疫组化、酶联免疫吸附测定（enzyme-linked immuno sorbent assay，ELISA）和差异蛋白质组学技术，观察和检测萎缩肝组织各种蛋白在肝腺泡中的分布特点和表达差异，探讨萎缩肝组织的病理特征和功能分化特征。结果 1、大体病理形态：萎缩肝叶/段体积缩小，局部肝表面纤维化，增生肝组织边沿球面化，萎缩与增生肝组织之间呈阶梯样结构改变，肝脏沿肝门轴旋转，肝门部右旋为主，胆总管后移，门静脉和肝动脉前移，门静脉前移至胆总管左侧； 2、超微结构：萎缩组织肝细胞线粒体、粗面内质网、高尔基体、滑面内质网均减少，毛细胆管微绒毛肿胀、稀少、崩解，周围有胶原纤维聚集；增生组织肝细胞线粒体、粗面内质网、高尔基体、滑面内质网、糖原颗粒含量丰富，毛细胆管微绒毛增生、密集； 3、蛋白表达分区特征：ALB、PEPCK主要在肝腺泡1区表达，L-FABP、GST和TPI主要在肝腺泡的3区表达，而Apo A-1主要在2区表达； 4、蛋白表达量的变化：免疫组化和ELISA显示，萎缩肝组织中各种蛋白质均有合成，但较增生肝组织均减少，其中，ALB、PEPCK、L-FABP、Apo A-1显著减少，而在肝腺泡3区合成的GST和TPI减少不显著。差异蛋白质组学检测发现，ALB、GDH、TPI、GAPDH、Apo A-1均减少，但GST未见明显减少。结论 1、肝脏AHC病变过程是一个患侧肝组织逐渐萎缩、功能逐渐减弱，和健侧肝组织代偿性增生、功能逐渐增强的过程； 2、萎缩肝组织仍有部分营养代谢和生物转化功能； 3、萎缩肝组织的肝腺泡也存在功能分化特性； 4、萎缩肝组织的营养代谢和生物转化功能对病变过程中肝组织维持正常生理功能有重要的过渡作用； 5、对于部分复杂的肝内胆管结石病人，由于萎缩肝组织能保留部分代谢功能和生物转化功能，保留萎缩肝叶的去胆管治疗或许既可以去除病因，又可以保留足够的肝组织来维持正常的肝脏生理功能。
[Abstract]:Background

Hepatic atrophy - hyperplasia complex ( AHC ) is due to the obstruction of portal vein , hepatic vein or bile duct , which leads to atrophy of hepatic tissue and compensatory hyperplasia of healthy side liver tissues .

method

From January 2008 to December 2013 , 28 cases of AHC were selected from January 2008 to December 2013 under the approval of the Ethics Committee of the Department of Ethics Committee of the General Hospital of PLA General Hospital .
Serum albumin ( ALB ) , glycerol - 3 - phosphate dehydrogenase ( TPI ) and glyceraldehyde - 3 - phosphate dehydrogenase ( PEPCK ) related to the metabolism and detoxification of fatty acids were selected in the liver tissues . The characteristics of liver fatty acid binding protein ( L - FABP ) related to the metabolism of fatty acids and the metabolism of cholesterol were measured by immunohistochemistry , enzyme - linked immunosorbent assay ( ELISA ) and differential proteomic technique .

Results

1 . Gross pathology : atrophy of liver lobe / segment volume , local liver surface fibrosis , hyperplasia of liver tissue margin , atrophy and hyperplasia of liver tissue , the structure of the ladder - like structure changes , the liver rotates along the hepatic portal axis , the hepatic portal is right - handed , the common bile duct is moved back , the portal vein and the hepatic artery move forward , the portal vein moves to the left side of the common bile duct ;

2 . Ultrastructure : The mitochondria , rough endoplasmic reticulum , golgi body and smooth endoplasmic reticulum of the atrophy tissue were reduced , and the microvilli of capillary bile duct were swollen , rare and disintegrated , and the surrounding collagen fibers were aggregated ;
The liver mitochondria , rough endoplasmic reticulum , golgi body , smooth endoplasmic reticulum , glycogen granules and capillary microvilli of hyperplasia tissue are abundant .

3 . Protein expression partitioning feature : ALB , PEPCK were mainly expressed in hepatic acinar 1 region , and L - FABP , GST and TPI were mainly expressed in three regions of hepatic acinar , while Apo A - 1 was mainly expressed in region 2 .

4 . Changes of protein expression : immunohistochemistry and ELISA showed that all kinds of protein in the atrophic liver tissue were synthesized , but there was no significant decrease in the amount of ALB , PEPCK , L - FABP and Apo A - 1 , but the expression of ALB , PEPCK , L - FABP and Apo A - 1 was reduced significantly .

Conclusion

1 . The process of hepatic AHC lesion is a process of gradually atrophy of the liver tissue in the affected side , the gradual decrease of the function , and the compensatory hyperplasia and function of the healthy side liver tissue ;

2 . Atrophic liver tissue still has some functions of nutrition metabolism and biotransformation ;

3 . The hepatic acinar of the atrophic liver tissue also has the function differentiation characteristic .

4 . The nutritional metabolism and biotransformation function of Atrophic liver tissue have important transitional effects on the normal physiological function of liver tissues during the course of pathological changes .

5 . For some complicated intrahepatic calculosis , the atrophy of the liver tissue can retain some metabolic function and biotransformation function , and it may not only remove the cause , but also keep enough liver tissue to maintain normal liver physiological function .

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R575

【参考文献】