本文選題：原發(fā)性膽汁性肝硬化 + LAMP2��； 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：研究背景 原發(fā)性膽汁性肝硬化（Primary biliary cirrhosis，PBC）是一種重要的自身免疫性肝病，西方國(guó)家報(bào)道發(fā)病率較高，年發(fā)病率波動(dòng)在0.39~1.5/106人，國(guó)內(nèi)尚無確切流行病學(xué)調(diào)查資料。其中大部分患者為中老年女性，男女患者比例約為1：9~10，近年其發(fā)病率呈增長(zhǎng)趨勢(shì)。PBC患者肝臟主要病理表現(xiàn)為肝內(nèi)小膽管慢性非化膿性炎癥，自身免疫性抗體持續(xù)作用于小膽管導(dǎo)致其進(jìn)行性破壞，最終發(fā)展為肝纖維及肝硬化。熊去氧膽酸（Ursodeoxychofic acid，UDCA）是美國(guó)食品藥品監(jiān)督局公布認(rèn)可的唯一對(duì)PBC治療有效的藥物，早期藥物干預(yù)效果良好，肝臟可長(zhǎng)期維持在代償期階段，明顯改善患者生存期，預(yù)后良好；但終末期PBC藥物治療效差，肝移植將是唯一有效治療。所以，早期診斷和早期治療是PBC診療的關(guān)鍵。因此，我們的研究擬通過分析PBC患者肝臟病理分期與血清學(xué)指標(biāo)間的關(guān)系，尋找能夠反映肝臟病理變化嚴(yán)重程度的血清學(xué)指標(biāo)，用以指導(dǎo)臨床工作中對(duì)PBC的診療工作。 針對(duì)病因治療是一切疾病治療的根本出發(fā)點(diǎn)，但PBC病因不明，發(fā)病機(jī)制不完全清楚，肝活檢組織病理學(xué)檢查提示有免疫功能異常參與。因此，尋找病因、探討發(fā)病機(jī)制仍是PBC研究的重點(diǎn)。溶酶體膜蛋白2（Lysosomal granulemembrane protein2，LAMP2）是一種新的抗中性粒細(xì)胞胞漿抗體(Antineutrophilcytoplasmic antibody，ANCA)，既往僅被認(rèn)為是一種單純結(jié)構(gòu)蛋白，現(xiàn)在的研究發(fā)現(xiàn)LAMP2亦參與調(diào)控自身免疫性疾病的發(fā)生。PBC作為一種自身免疫性疾病，LAMP2是否參與其發(fā)生發(fā)展過程？國(guó)內(nèi)有少量報(bào)道提示二者之間存在相關(guān)性。因此，我們的研究擬通過免疫組織化學(xué)法觀察LAMP2在肝臟的表達(dá)，分析其表達(dá)強(qiáng)度與肝臟病理分期及血清學(xué)指標(biāo)的關(guān)系，探討LAMP2在PBC發(fā)展過程中的可能作用。 研究目的 分析PBC患者肝活檢肝臟病理分期、LAMP2表達(dá)強(qiáng)度及血清學(xué)指標(biāo)三者間的關(guān)系，探討LAMP2在PBC發(fā)展過程中的可能作用。 材料與方法 登記2003年6月至2012年12月于鄭州大學(xué)第一附屬醫(yī)院經(jīng)肝活檢組織病理學(xué)檢查確診為PBC的45例患者，收集臨床資料、肝活檢同期肝功能、凝血功能、免疫球蛋白、ANA、AMA、AMA-M2及肝活檢組織蠟塊，切片后運(yùn)用H-E染色觀察肝臟病理變化，按照Scheuer組織學(xué)分期法分Ⅰ期、Ⅱ期、Ⅲ+Ⅳ期，并運(yùn)用免疫組織化學(xué)方法觀察LAMP2在PBC患者肝臟的表達(dá)，分析蛋白表達(dá)強(qiáng)度與病理分期間的關(guān)系，觀察不同病理分期及不同LAMP2表達(dá)強(qiáng)度下肝功能、凝血功能、免疫球蛋白、ANA、AMA、AMA-M2等血清學(xué)指標(biāo)的變化趨勢(shì)。 結(jié)果 1. LAMP2在PBC患者肝臟中表達(dá)強(qiáng)度與肝臟病理分期間呈正相關(guān)，相關(guān)系數(shù)(r)為0.555(P0.05)。 2.血清γ-GT、ALP、DBIL、ALB水平與PBC肝臟病理分期間存在相關(guān)性，相關(guān)系數(shù)(r)分別為0.318、0.305、0.410和-0.295(P值分別為0.033、0.041、0.005和0.049)，其中DBIL在不同病理分期中位值差異具有統(tǒng)計(jì)學(xué)意義（χ2=8.691，P=0.013）；γ-GT、ALP、DBIL及IgG與不同肝臟病理分期間行ROC曲線分析中，僅γ-GT對(duì)Ⅲ+Ⅲ期PBC診斷的ROC曲線下面積為0.709，余者ROC曲線下面積均小于0.7。PT、FIB、IgG、IgM、ANA、AMA、AMA-M2與PBC患者肝臟病理分期間無相關(guān)性。3.血清γ-GT、ALP、DBIL、ALB水平與LAMP2表達(dá)強(qiáng)度間存在相關(guān)性，相關(guān)系數(shù)(r)分別為0.578、0.522、0.479和-0.335(P值分別為0.000、0.000、0.001和0.024)，且血清γ-GT、ALP、DBIL、ALB水平在不同LAMP2表達(dá)強(qiáng)度下中位值差異均具有統(tǒng)計(jì)學(xué)意義（統(tǒng)計(jì)值分別為14.877、13.829、10.215、7.774，P值分別別0.001、0.001、0.006、0.021）。PT、FIB、IgG、IgM、ANA、AMA、AMA-M2與PBC患者肝臟LAMP2表達(dá)強(qiáng)度間無相關(guān)性。 結(jié)論 1.LAMP2在PBC患者肝臟組織中的表達(dá)強(qiáng)度與肝功能及肝臟病理分期間均存在相關(guān)性，，提示LAMP2在肝臟異常表達(dá)可能參與PBC發(fā)展過程。 2.血清γ-GT、ALP、DBIL、ALB水平與PBC患者肝臟病理分期間存在相關(guān)性，且γ-GT對(duì)Ⅲ+Ⅲ期PBC診斷的ROC曲線下面積大于0.7，提示肝功能指標(biāo)可用于臨床對(duì)PBC肝臟病理分期的判斷，其中以γ-GT價(jià)值最大。
[Abstract]:Background of the study

Primary biliary cirrhosis ( PBC ) is an important autoimmune liver disease . Most of the patients are middle - aged and middle - aged women , and the annual incidence fluctuation is 0.39 - 1.5 / 106 . Most of the patients are middle - aged and old women . The proportion of patients and women is about 1 : 9 - 10 . In recent years , the incidence of chronic non - suppurative inflammation of the intrahepatic ducts leads to progressive destruction of liver and cirrhosis . Ursodeoxychofic acid ( UDCA ) is the only drug effective to PBC for the treatment of liver fibrosis and cirrhosis . Ursodeoxychofic acid ( UDCA ) is the only drug effective for PBC . It can obviously improve the survival time and prognosis of patients .
Therefore , early diagnosis and early treatment are the key to the diagnosis and treatment of PBC . Therefore , we intend to find a serological index which can reflect the severity of liver pathological changes by analyzing the relationship between pathological stage and serological index of liver pathological changes in PBC patients , which is used to guide the diagnosis and treatment of PBC in clinical work .

In this paper , we study the relationship between the expression intensity of LAMP2 and the pathological stage and serological index of liver , and explore the possible role of LAMP2 in the development of PBC .

Purpose of study

The relationship between the pathological stage , the expression intensity of LAMP2 and the serological index of liver biopsy in PBC patients was analyzed , and the possible role of LAMP2 in the development of PBC was discussed .

Materials and Methods

In the first Affiliated Hospital of Zhengzhou University from June 2003 to December 2012 , 45 patients with PBC were diagnosed as PBC , clinical data were collected , liver function , blood coagulation function , immunoglobulin , ANA , AMA , AMA - M2 and liver biopsy tissue wax blocks were observed .

Results

1 . The expression intensity of LAMP2 in liver of PBC was positively correlated with the pathological score of liver , and the correlation coefficient ( r ) was 0.555 ( P0.05 ) .

2 . There was a correlation between serum 緯 - GT , ALP , DBIL , ALB and pathological score of PBC . The correlation coefficients ( r ) were 0.318 , 0.305 , 0.410 and - 0.295 ( P values were 0.033 , 0.041 , 0.005 and 0.049 , respectively ) .
There was no correlation between the levels of 緯 - GT , ALP , DBIL , ALB and the expression intensity of LAMP2 . There was no correlation between the levels of 緯 - GT , ALP , DBIL , ALB and the expression intensity of LAMP2 . The correlation coefficients ( r ) were 0.578 , 0.522 , 0.479 and - 0.335 ( P = 0.000 , 0.001 , 0.006 , 0.021 ) respectively .

Conclusion

1 . The expression intensity of LAMP2 in liver tissues of PBC patients was correlated with liver function and liver pathology , suggesting that LAMP2 might be involved in the development of PBC .

2 . The serum 緯 - GT , ALP , DBIL , ALB levels were correlated with the pathological division of liver in PBC patients , and the area of 緯 - GT was more than 0.7 under ROC curve of PBC diagnosis 鈪

本文編號(hào)：1786916