机构地区:[1]山西医科大学第一医院感染病科,太原030001 [2]山西医科大学肝病研究所
出 处:《中华传染病杂志》2011年第8期474-479,共6页Chinese Journal of Infectious Diseases
基 金:山西省自然科学基金项目(2007011118)
摘 要:目的探讨慢性乙型肝炎(cHB)患者树突状细胞(Dc)与肠源性内毒素血症(IETM)的关系。方法CHB患者80例,健康对照者21例,采集外周血,测定血浆内毒素含量、ALT、TBil。根据血浆内毒素水平,将患者分为内毒素阳性组和阴性组。同时用重组人粒细胞巨噬细胞集落刺激因子、重组人白细胞介素-4、酪氨酸激酶受体3配体和TNF-α体外诱导、培养CHB患者DC,采用流式细胞仪检测DC表型,混合淋巴细胞反应检测DC刺激T淋巴细胞的能力,用ELISA检测DC分泌细胞因子的水平。多组间比较采用单因素方差分析。结果CHB患者DC表达CD83、CD80、CD86和人类白细胞抗原(HLA)-DR分子的水平及诱导同种异体混合T淋巴细胞增殖的能力均明显低于健康对照组。内毒素阳性组患者表达CD83、CD80、CD86、HLA-DR水平及诱导T淋巴细胞增殖的能力分别为(8.25±3.63)%、(10.63±4.52)%、(36.61±16.16)%、(61.65±14.33)%、0.812±0.311,明显低于内毒素阴性组的(11.39±4.35)%、(13.56±5.13)%、(45.90±15.35)%、(70.35±18.89)0.4、1.153±0.324(F=5.123、4.213、3.714、3.323、3.125,均P〈0.05)。培养至第9天,CHB患者DC分泌IL-12和IFN-γ分别为(16.99±6.74)pg/mL和(10.52±4.19)pg/mL,明显低于健康者的(44.51±14.56)pg/mL和(17.94±5.86)pg/mL。内毒素阳性组患者IL-12水平为(13.14士5.71)pg/mL,明显低于内毒素阴性组的(20.98±9.03)pg/mL(F=3.225,P=0.016)。IFN-γ水平在内毒素阳性组为(9.46±3.24)pg/mL,与阴性组的(1t.54±5.20)pg/mL比较,差异无统计学意义(F=2.003,P=0.076)。结论IETM是导致CHB患者体内DC功能异常的原因之一。Objective To investigate the relationship between dendritic cell (DC) and intestinal endotoxemia in patients with chronic hepatitis B (CHB). Methods Peripheral blood were collected from CHB patients (n = 80) and healthy controls (n = 21). Plasma endotoxin (ET) levels, liver function (alanine transaminase, total bilirubin) were detected. According to plasma ET concentration, all CHB patients were divided into two groups: ET positive and ET negative. The peripheral blood mononuclear cells (PBMCs) were isolated and then cultured with recombinant human granulocyte- macrophage colony-stimulating factor (rhGM-CSF), recombinant human interleukin-4 (rhIL-4),FMS-related tyrosine kinase 3 ligand (Fh3L) and tumor necrosis factor-alpha (TNF-a) to derive DC. The phenotypic patterns were characterized by flow cytometry. The proliferation of T lymphocytes was evaluated with mixed leukocytes reaction (MLR) and the levels of IL-12 and interferon-γ (IFN-γ) produced by DC were analyzed with enzyme-linked immunosorbent assay (ELISA). Comparisons among the two groups and healthy control group were done by single factor analysis of variance. Results Compared to healthy controls, the expressions of CD83, CD80, CD86, human leucocyte antigen (HLA)-DR and the proliferation of allogeneic T lymphocytes by DC were all significantly reduced in CHB patient groups. The expressions of CD83, CD80, CD86, HLA-DR and the activation of proliferation in ET positive subjects were lower than those in ET negative subjects [CD83 (8.25 ± 3.63)% vs (11.39±4. 35)% , CD80 (10. 63±4. 52)% vs (13. 56±5.13)%, CD86 (36. 61±16.16)% vs (45.90±15.35)%, HLA-DR (61. 65±14.33)% vs (70.35±18.89)%, the activation of proliferation 0. 812±0. 311 vs 1. 153±0. 324; F=5. 123, 4. 213, 3.714, 3. 323 and 3. 125, respectively; all P〈0.05]. After cultured for 9 days, the secretions of IL-12 and IFN-γ by DC were significantly lower in CHB patients than in healthy controls [I
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