原发性胆汁性肝硬化病理分期、LAMP2表达及血清学指标的关系

发布时间：2018-04-22 11:06

  本文选题：原发性胆汁性肝硬化 + LAMP2　； 参考：《郑州大学》2014年硕士论文

【摘要】：研究背景 原发性胆汁性肝硬化（Primary biliary cirrhosis，PBC）是一种重要的自身免疫性肝病，西方国家报道发病率较高，年发病率波动在0.39~1.5/106人，国内尚无确切流行病学调查资料。其中大部分患者为中老年女性，男女患者比例约为1：9~10，近年其发病率呈增长趋势。PBC患者肝脏主要病理表现为肝内小胆管慢性非化脓性炎症，自身免疫性抗体持续作用于小胆管导致其进行性破坏，最终发展为肝纤维及肝硬化。熊去氧胆酸（Ursodeoxychofic acid，UDCA）是美国食品药品监督局公布认可的唯一对PBC治疗有效的药物，早期药物干预效果良好，肝脏可长期维持在代偿期阶段，明显改善患者生存期，预后良好；但终末期PBC药物治疗效差，肝移植将是唯一有效治疗。所以，早期诊断和早期治疗是PBC诊疗的关键。因此，我们的研究拟通过分析PBC患者肝脏病理分期与血清学指标间的关系，寻找能够反映肝脏病理变化严重程度的血清学指标，用以指导临床工作中对PBC的诊疗工作。 针对病因治疗是一切疾病治疗的根本出发点，但PBC病因不明，发病机制不完全清楚，肝活检组织病理学检查提示有免疫功能异常参与。因此，寻找病因、探讨发病机制仍是PBC研究的重点。溶酶体膜蛋白2（Lysosomal granulemembrane protein2，LAMP2）是一种新的抗中性粒细胞胞浆抗体(Antineutrophilcytoplasmic antibody，ANCA)，既往仅被认为是一种单纯结构蛋白，现在的研究发现LAMP2亦参与调控自身免疫性疾病的发生。PBC作为一种自身免疫性疾病，LAMP2是否参与其发生发展过程？国内有少量报道提示二者之间存在相关性。因此，我们的研究拟通过免疫组织化学法观察LAMP2在肝脏的表达，分析其表达强度与肝脏病理分期及血清学指标的关系，探讨LAMP2在PBC发展过程中的可能作用。 研究目的 分析PBC患者肝活检肝脏病理分期、LAMP2表达强度及血清学指标三者间的关系，探讨LAMP2在PBC发展过程中的可能作用。 材料与方法 登记2003年6月至2012年12月于郑州大学第一附属医院经肝活检组织病理学检查确诊为PBC的45例患者，收集临床资料、肝活检同期肝功能、凝血功能、免疫球蛋白、ANA、AMA、AMA-M2及肝活检组织蜡块，切片后运用H-E染色观察肝脏病理变化，按照Scheuer组织学分期法分Ⅰ期、Ⅱ期、Ⅲ+Ⅳ期，并运用免疫组织化学方法观察LAMP2在PBC患者肝脏的表达，分析蛋白表达强度与病理分期间的关系，观察不同病理分期及不同LAMP2表达强度下肝功能、凝血功能、免疫球蛋白、ANA、AMA、AMA-M2等血清学指标的变化趋势。 结果 1. LAMP2在PBC患者肝脏中表达强度与肝脏病理分期间呈正相关，相关系数(r)为0.555(P0.05)。 2.血清γ-GT、ALP、DBIL、ALB水平与PBC肝脏病理分期间存在相关性，相关系数(r)分别为0.318、0.305、0.410和-0.295(P值分别为0.033、0.041、0.005和0.049)，其中DBIL在不同病理分期中位值差异具有统计学意义（χ2=8.691，P=0.013）；γ-GT、ALP、DBIL及IgG与不同肝脏病理分期间行ROC曲线分析中，仅γ-GT对Ⅲ+Ⅲ期PBC诊断的ROC曲线下面积为0.709，余者ROC曲线下面积均小于0.7。PT、FIB、IgG、IgM、ANA、AMA、AMA-M2与PBC患者肝脏病理分期间无相关性。3.血清γ-GT、ALP、DBIL、ALB水平与LAMP2表达强度间存在相关性，相关系数(r)分别为0.578、0.522、0.479和-0.335(P值分别为0.000、0.000、0.001和0.024)，且血清γ-GT、ALP、DBIL、ALB水平在不同LAMP2表达强度下中位值差异均具有统计学意义（统计值分别为14.877、13.829、10.215、7.774，P值分别别0.001、0.001、0.006、0.021）。PT、FIB、IgG、IgM、ANA、AMA、AMA-M2与PBC患者肝脏LAMP2表达强度间无相关性。 结论 1.LAMP2在PBC患者肝脏组织中的表达强度与肝功能及肝脏病理分期间均存在相关性，，提示LAMP2在肝脏异常表达可能参与PBC发展过程。 2.血清γ-GT、ALP、DBIL、ALB水平与PBC患者肝脏病理分期间存在相关性，且γ-GT对Ⅲ+Ⅲ期PBC诊断的ROC曲线下面积大于0.7，提示肝功能指标可用于临床对PBC肝脏病理分期的判断，其中以γ-GT价值最大。
[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 纬 - 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 纬 - GT , ALP , DBIL , ALB and the expression intensity of LAMP2 . There was no correlation between the levels of 纬 - 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 纬 - GT , ALP , DBIL , ALB levels were correlated with the pathological division of liver in PBC patients , and the area of 纬 - GT was more than 0.7 under ROC curve of PBC diagnosis 鈪

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