本文選題：萎縮-增生復(fù)合征 + 病理學(xué)　； 參考：《中國人民解放軍醫(yī)學(xué)院》2014年博士論文

【摘要】：背景 肝萎縮-增生復(fù)合征（the atrophy-hypertrophy complex，AHC）是由于門靜脈、肝靜脈或膽管的梗阻，導(dǎo)致梗阻支配區(qū)域的肝組織萎縮和健側(cè)肝組織的代償性增生。肝內(nèi)膽管結(jié)石和肝門部膽管癌常引起AHC。部分復(fù)雜的肝內(nèi)膽管結(jié)石常因殘余肝太少而無法手術(shù)切除，病變的萎縮肝組織對維持正常肝功能可能具有重要意義。對于肝門部膽管癌等需要行擴(kuò)大半肝切除的病人術(shù)前行門靜脈栓塞（Portal vein embolization，，PVE），使患側(cè)肝萎縮和健側(cè)肝代償性增生，在此代償過程中，萎縮肝組織對機(jī)體維持正常肝功能也可能起著重要作用。肝腺泡是肝臟的結(jié)構(gòu)和功能的基本單位，具有功能分化特征。目前對AHC萎縮肝組織的病理和功能特征的研究極少。本課題擬選取AHC術(shù)后萎縮和增生肝組織行自身對照研究，探討AHC萎縮肝組織的病理變化和功能特征。 方法 在解放軍總醫(yī)院三0四臨床部倫理委員會的批準(zhǔn)下和患者的知情同意下，選取2008年1月至2013年12月AHC病例28例，包括肝內(nèi)膽管結(jié)石24例和肝門部膽管癌4例。在肝部分切除后將萎縮和增生肝組織行自身對照研究，觀察萎縮肝組織的大體形態(tài)改變，并在光鏡下觀察萎縮肝組織的病理改變，在掃描電鏡下觀察萎縮組織肝細(xì)胞超微結(jié)構(gòu)變化；選取肝組織中與營養(yǎng)代謝和解毒功能有關(guān)的白蛋白（albumin， ALB）、與糖酵解有關(guān)的磷酸丙糖異構(gòu)酶（triosephosphate isomerase, TPI）和甘油醛-3-磷酸脫氫酶（glyceraldehyde-3-phosphate dehydrogenase，GAPDH）、與有氧氧化和糖異生有關(guān)的磷酸烯醇丙酮酸羧激酶（phosphoenolpyruvate carboxykinase,PEPCK）、與膽固醇代謝有關(guān)的載脂蛋白A-1（apolipoprotein A-1，Apo A-1）、與氨基酸代謝有關(guān)的谷氨酸脫氫酶（glutamate dehydrogenase，GDH）、與脂肪酸代謝和色素形成有關(guān)的肝臟脂肪酸結(jié)合蛋白（liver fatty acid bindingprotein，L-FABP）以及與生物轉(zhuǎn)化和膽紅素運(yùn)輸有關(guān)的谷胱甘肽轉(zhuǎn)移酶（glutathione S-transferase, GST）作為觀察指標(biāo)，利用免疫組化、酶聯(lián)免疫吸附測定（enzyme-linked immuno sorbent assay，ELISA）和差異蛋白質(zhì)組學(xué)技術(shù)，觀察和檢測萎縮肝組織各種蛋白在肝腺泡中的分布特點(diǎn)和表達(dá)差異，探討萎縮肝組織的病理特征和功能分化特征。 結(jié)果 1、大體病理形態(tài)：萎縮肝葉/段體積縮小，局部肝表面纖維化，增生肝組織邊沿球面化，萎縮與增生肝組織之間呈階梯樣結(jié)構(gòu)改變，肝臟沿肝門軸旋轉(zhuǎn)，肝門部右旋為主，膽總管后移，門靜脈和肝動脈前移，門靜脈前移至膽總管左側(cè)； 2、超微結(jié)構(gòu)：萎縮組織肝細(xì)胞線粒體、粗面內(nèi)質(zhì)網(wǎng)、高爾基體、滑面內(nèi)質(zhì)網(wǎng)均減少，毛細(xì)膽管微絨毛腫脹、稀少、崩解，周圍有膠原纖維聚集；增生組織肝細(xì)胞線粒體、粗面內(nèi)質(zhì)網(wǎng)、高爾基體、滑面內(nèi)質(zhì)網(wǎng)、糖原顆粒含量豐富，毛細(xì)膽管微絨毛增生、密集； 3、蛋白表達(dá)分區(qū)特征：ALB、PEPCK主要在肝腺泡1區(qū)表達(dá)，L-FABP、GST和TPI主要在肝腺泡的3區(qū)表達(dá)，而Apo A-1主要在2區(qū)表達(dá)； 4、蛋白表達(dá)量的變化：免疫組化和ELISA顯示，萎縮肝組織中各種蛋白質(zhì)均有合成，但較增生肝組織均減少，其中，ALB、PEPCK、L-FABP、Apo A-1顯著減少，而在肝腺泡3區(qū)合成的GST和TPI減少不顯著。差異蛋白質(zhì)組學(xué)檢測發(fā)現(xiàn)，ALB、GDH、TPI、GAPDH、Apo A-1均減少，但GST未見明顯減少。 結(jié)論 1、肝臟AHC病變過程是一個患側(cè)肝組織逐漸萎縮、功能逐漸減弱，和健側(cè)肝組織代償性增生、功能逐漸增強(qiáng)的過程； 2、萎縮肝組織仍有部分營養(yǎng)代謝和生物轉(zhuǎn)化功能； 3、萎縮肝組織的肝腺泡也存在功能分化特性； 4、萎縮肝組織的營養(yǎng)代謝和生物轉(zhuǎn)化功能對病變過程中肝組織維持正常生理功能有重要的過渡作用； 5、對于部分復(fù)雜的肝內(nèi)膽管結(jié)石病人，由于萎縮肝組織能保留部分代謝功能和生物轉(zhuǎn)化功能，保留萎縮肝葉的去膽管治療或許既可以去除病因，又可以保留足夠的肝組織來維持正常的肝臟生理功能。
[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 .

【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R575

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