MCP-1介导单核细胞浸润在泡型包虫病肝纤维化中的作用  

Role of monocyte chemotactic protein 1-mediated monocyte infiltration in liver fibrosis of alveolar echinococcosis

作　　者：闵宏悦 田凤鸣 张靖仪 齐新伟 姜涛[4] 李佳峻 张雪 施宁 刘玉梅 马秀敏 MIN Hong-yue;TIAN Feng-ming;ZHANG Jing-yi;QI Xin-wei;JIANG Tao;LI Jia-jun;ZHANG Xue;SHI Ning;LIU Yu-mei;MA Xiu-min(State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Laboratory Center,Tumor Hospital Affiliated to Xinjiang Medical University,Urumqi 830011,China;School of Basic Medicine,Xinjiang Medical University;State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,First Affiliated Hospital of Xinjiang Medical University;Animal Experiment Center,Xinjiang Medical University;Beijing Children's Hospital Xinjiang Hospital,Xinjiang Uygur Autonomous Region Children's Hospital)

机构地区：[1]新疆医科大学附属肿瘤医院临床检验中心,省部共建中亚高发病成因与防治国家重点实验室,新疆乌鲁木齐830011 [2]新疆医科大学基础医学院 [3]新疆医科大学第一附属医院临床医学研究院省部共建中亚高发病成因与防治国家重点实验室 [4]新疆医科大学动物实验中心 [5]北京儿童医院新疆医院,新疆维吾尔自治区儿童医院

出　　处：《中国病原生物学杂志》2023年第4期400-405,410,共7页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.82060372);新疆维吾尔自治区科技支疆项目(No.2020E0277);省部共建中亚高发病成因与防治国家重点实验室开放课题项目(No.SKL-HIDCA-2020-YG3,SKL-HIDCA-2020-50,SKL-HID CA-2021-5)。

摘　　要：目的探讨肝泡型包虫病患者肝组织中单核细胞趋化蛋白1(MCP-1)表达水平与单核细胞来源巨噬细胞浸润程度、炎症及纤维化的相关性。方法采用苏木素-伊红(H&E)染色和Masson染色评估病理炎症改变和纤维化程度,采用免疫组织化学方法检测肝组织中CD68^(+)巨噬细胞和MAC387^(+)单核细胞来源的巨噬细胞浸润情况及MCP-1表达情况,采用实时荧光定量PCR(qRT-PCR)检测肝脏组织中MCP-1的基因表达,采用酶联免疫吸附试验(ELISA)检测外周血中MCP-1水平,并分析MCP-1与MAC387^(+)单核细胞来源巨噬细胞浸润的相关性,以及与肝组织炎症和纤维化的关系。结果H&E染色显示,与灶旁肝脏组织相比近端病灶组织肝小叶结构被破坏,病变周围可见炎症细胞浸润。Masson染色显示近端病灶组织门静脉区域纤维结缔组织增生,肝小叶纤维化,而灶旁肝脏组织未见明显病理改变。免疫组织化学检测显示,与灶旁肝脏组织相比近端病灶组织中CD68^(+)巨噬细胞和MAC387^(+)单核细胞来源的巨噬细胞均显著增加(均P<0.01),灶旁肝脏组织中MCP-1表达较少,而近端病灶组织MCP-1高表达(P<0.01)。相关性分析显示,肝脏组织中MCP-1的表达与MAC387^(+)单核细胞来源的巨噬细胞表达水平呈显著正相关(R=0.814,P<0.01),与肝脏炎症的严重程度呈正相关(R=0.813,P<0.01),与纤维化评分呈正相关(R=0.719,P<0.01)。qRT-PCR检测显示,近端病灶组织中MCP-1mRNA表达水平显著高于灶旁肝脏组织(P<0.05)。ELISA检测显示,与健康体检者相比肝泡型包虫病患者外周血中MCP-1水平显著升高(P<0.01)。结论MCP-1与肝泡型包虫病导致的肝脏炎症和纤维化程度呈正相关,与MAC387^(+)单核细胞来源的巨噬细胞数量呈正相关,提示MCP-1可能介导肝组织中单核细胞的浸润。因此推测MCP-1在肝泡型包虫病肝纤维化中具有重要作用。Objective To investigate the correlation between the expression level of monocyte chemotactic protein 1(MCP-1)and the degree of monocyte-derived macrophage infiltration,inflammation and fibrosis in liver tissue from patients with hepatic alveolar echinococcosis(hepatic AE)disease.Methods In this study,liver tissue and blood samples were collected from 33 patients with hepatic AE at the First Affiliated Hospital of Xinjiang Medical University.The liver tissue specimens were divided into proximal focal tissue and parafocal liver tissue.HE and Masson staining were used to evaluate the pathological inflammatory changes and the degree of fibrosis;immunohistochemistry was used to detect the infiltration of CD68^(+)macrophages and MAC387^(+)monocyte-derived macrophages and MCP-1 expression.Total RNA was extracted from liver samples and cDNA was synthesised to detect MCP-1 gene expression by qRT-PCR.In addition,33 healthy controls'blood samples were collected and MCP-1 levels were measured by ELISA.Spearman correlation was used to analyse the correlation between MCP-1 and MAC387^(+)monocyte-derived macrophage infiltration,as well as the relationship with inflammation and fibrosis in liver tissue.Results HE staining showed disruption of the proximal lobular structure and inflammatory cell infiltration around the lesion compared to the parafocal liver tissue.Masson staining showed hyperplasia of fibrous connective tissue in the portal vein region and fibrosis of the lobules in the proximal lesion,while no significant pathological changes were seen in the parafocal liver tissue.Immunohistochemistry showed that CD68^(+)macrophages(54.61±30.05)and MAC387^(+)monocyte-derived macrophages(109.94±32.58)were significantly increased in the proximal focal tissue compared to the parafocal liver tissue CD68^(+)macrophages(2.79±1.71)and MAC387^(+)monocyte-derived macrophages(3.64±2.83)(all P0.01),and MCP-1 expression(0.48±0.71)was lower in parafocal liver tissue,whereas MCP-1 was highly expressed in proximal focal tissue(7.48±3.5

关 键 词：肝泡型包虫 巨噬细胞 MCP-1 

分 类 号：R532.32[医药卫生—内科学]