中文摘要：

目的 研究Th17细胞与TGF-β1在PBC不同分期间的差异,探讨二者在PBC病程不同阶段发病机制中的作用.方法 采用流式细胞术检测外周血Th17细胞水平,实时荧光定量（RT）-PCR方法检测PBMCs中IL-17A及TG F-β1的mRNA水平,ELISA方法检测血清TGF-β1水平,肝活检标本进行病理分期.早、晚期PBC、慢性乙型病毒性肝炎及健康对照组间Th17细胞占CD4＋细胞比例采用Krustal-Wallis检验,随后采用Mann-Whitney U检验两两比较,各组间IL-17 mRNA、TGF-β1 mRNA水平、血清TGF-β1浓度采用单因素方差分析,随后采用LSD法两两比较,PBC患者外周血Th17细胞比例及血清TGF-β1浓度与Mayo评分的相关性分析采用Pearson相关分析.结果 早期PBC患者外周血Th17细胞比例（1.03±0.33）％显著高于乙型肝炎对照组[（0.56±0.35）％,U=104.5,P＜0.01]和健康对照组[（0.36±0.17）％,U=8.0,P＜0.01],而晚期PBC患者较早期组明显下降[（0.48±0.13）％,U=14.0,P＜0.01].相反,TGF-β1在PBC早期（30±12） ng/ml与健康对照组（39±11） ng/ml差异无统计学意义（t=-1.02,P=0.314）,而PBC晚期较早期明显升高[（43±19） ng/ml,t=2.85,P=0.006].结论 Th17细胞与TGF-β1均参与PBC的发病机制,但二者的作用机制与时机不同.Th17细胞主要作用于疾病早期,参与自身免疫性炎症的发生,TGF-β1主要作用于疾病晚期,对肝纤维化的形成具有重要作用,而在疾病早期可能表现为对Th17细胞分化的调节作用。

英文摘要：

Objective To explore the differences of Th17 population and serum transforming growth factor （TGF）-β1 levels between early-and late-stage primary biliary cirrhosis （PBC） and their roles in pathogenesis.Methods Peripheral Th17 counts were analyzed by flow cytometry.The expression of IL-17A in peripheral blood mononuclear cells and TGF-β1 were measured by real-time quantitative polymerase chain reaction.Serum concentration of TGF-β1 was measured by enzyme-linked immunosorbent assay.Liver biopsies were stained with hematoxylin-eosin to determine the pathological stage.Results were evaluated using KrustalWallis test followed by Mann-Whitney U tests for comparisons of Th17 population between patients with early and late PBC,patients with chronic hepatitis B （CHB） and health controls （HCs）.ANOVA followed by LSD t-tests were used for comparing IL-17 mRNA,TGF-β1 mRNA and TGF-β1 serum concentration between groups.The correlations between Mayo risk score and peripheral Th17 of PBC patients,Mayo risk score and serum concentration of TGF-β1 was analyzed by Pearson correlation analysis separately.Results The peripheral Th17 population increased in patients with early PBC （1.03±0.33）%,compared to those with late PBC [（0.48± 0.13%,U=14.0,P〈0.01],CHB [（0.56±0.35）%,U=104.5,P〈0.01],and HCs [（0.36±0.17）%,U=8.0,P〈0.01],while TGF-β1 changed in the opposite direction.Serum concentration of TGF-β1 elevated in late PBC （43.0± 18.7） ng/ml compared with early PBC （29.5±12.2） ng/ml,t=2.85,P=0.006.Conclusion The opposite changes of Th17 population and TGF-β1 level in early and late PBC indicated their different roles in different stages.Th17 may contribute to the autoimmune response in early PBC,participate in the occurrence of autoimmune inflammation,while TGF-β1 to fibrogenesis in late stage.In addition,the possible regulation mechanisms of differentiation of Th17 by TGF-β1 cannot be ignored.