摘要
目的探讨IL-17+CD4+T细胞(Th17细胞)在乙肝肝硬化患者中的免疫致病机制。方法选择2008年7月-2011年12月收治的乙肝肝硬化患者60例及健康对照30名,采用流式细胞仪检测外周血Th17细胞频率及IL-17受体表达情况,ELISA法检测外周血血浆中IL-17水平,并检测IL-17刺激后人肝星状细胞LX-2中α-平滑肌肌动蛋白(α-SMA)及细胞因子IL-6、IL-8和IL-23p19的表达情况。结果与健康对照相比,乙肝肝硬化患者外周血Th17细胞频率和血浆IL-17浓度均显著升高(P<0.01),Th17细胞频率随肝功能损害程度的加重而增高,Child分级C级患者体内Th17频率最高,与A级患者相比差异有统计学意义(P<0.05)。LX-2细胞在IL-17刺激后IL-17受体表达上调,同时α-SMA表达也明显上调(P<0.05),并产生了炎症相关细胞因子IL-6、IL-8和IL-23p19。结论 Th17细胞的增加不但与乙肝肝硬化患者肝功能损害程度密切相关,而且通过分泌IL-17促进了肝星状细胞的活化,加快了肝硬化的疾病进程。
Objective To explore the immunopathogenesis of IL-17+CD4+ T cells(Th17 cells) in patients with HBV-associated liver cirrhosis(HBV-LC).Methods Sixty patients with HBV-LC admitted from Jul.2008 to Dec.2011 were enrolled in present study.Thirty matched individuals served as control.The frequencies of circulating Th17 cells and IL-17 receptor expression were detected by flow cytometry.The IL-17 level in plasma was determined by ELISA.The expression of smooth muscle actin(α-SMA) in human hepatic stellate cells(HSCs) LX-2 stimulated by IL-17(1ng/ml) was detected by flow cytometry,while the inflammation-associated cytokines,including IL-6,IL-8 and IL-23p19,were determined by ELISA.Results Both the frequency of circulating Th17 cells and the concentration of IL-17 in plasma increased significantly in HBV-LC patients when compared with those in healthy controls(P0.01).In HBV-LC patients,Th17 frequency increased along with the severity of liver disease.The highest level of Th17 cells appeared in Child-Pugh C patients,and it showed a statistically significant difference when compared with that in Child-Pugh A patients(P〈0.05).In addition,when LX-2 cells were stimulated with IL-17,not only were the expressions of IL-17R and α-SMA up-regulated(P〈0.05),but also more inflammation-associated cytokines,including IL-6,IL-8 and IL-23p19,were produced.Conclusion Increase of peripheral Th17 cells may be closely associated with progression of severity of disease in HBV-LC patients,promote HSCs activation by secretion of IL-17,and accordingly accelerate the disease progression.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2013年第1期62-65,共4页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金(81072424
30801039)
国家重点基础研究计划(2007CB512805)~~
关键词
T淋巴细胞亚群
肝炎
乙型
慢性
肝硬化
T-lymphocyte subsets
hepatitis B
chronic
liver cirrhosis