不同阶段原发性胆汁性肝硬化患者经不同剂量熊去氧胆酸治疗后外周血T淋巴细胞亚群及细胞因子的变化

Changes in T lymphocyte subsets and cytokines in peripheral blood of patients with primary biliary cirrhosis after treatment with different doses of ursodeoxycholic acid

目的探讨不同治疗剂量的熊去氧胆酸（UDCA）对不同时期原发性胆汁性肝硬化（PBC）患者的免疫学改善程度,为临床PBC的规范化治疗提供依据。方法选取2012年3月-2014年1月新疆生产建设兵团医院住院及门诊收治的180例PBC患者,依据病变程度将患者分为PBC早期、PBC肝硬化期和PBC对生化应答不佳期,各60例。按照8~10、13~15、20~25mg·kg^-1·d^-1不同剂量的UDCA治疗将每类患者再分成3组,每组20例。对患者的一般资料、临床表现、生化指标和不同剂量UDCA治疗前后外周血T淋巴细胞亚群及细胞因子的变化进行分析。计量资料两组间比较采用t检验,多组间比较采用单因素方差分析,进一步两两比较采用SNK-q检验。计数资料组间比较采用χ2检验。结果与治疗前相比,应用13~15 mg·kg^-1·d^-1剂量UDCA治疗后的PBC早期患者其CD3＋CD4＋细胞百分比[（54.8±11.6）%vs（34.7±7.7）%]、CD4＋/CD8＋比值[（2.3±1.0）vs（1.6±0.6）]及干扰素γ的水平[（33.0±12.3）ng/L vs（23.7±7.2）ng/L]显著降低,白细胞介素4的分泌量[（29.0±4.6）ng/L vs（38.5±7.1）ng/L]显著增加,差异均有统计学意义（t值分别为6.5、2.7、2.9、5.0,P值均〈0.05）。结论 13~15mg·kg^-1·d^-1剂量的UDCA治疗PBC早期患者可显著改善其免疫状况,应规范使用UDCA以充分发挥其应答效果。

Objectlve To investigate the immunological improvement effects of different doses of ursodeoxycholic acid （UDCA） on patients with different stages of primary biliary cirrhosis （PBC） and enhance the understanding of the roles of the immune system in the disease, and to provide evidence for the standardized clinical treatment of PBC. Methods One hundred and eighty patients with PBC who were admitted to our hospital from March 2012 to Janurary 2014 were enrolled and equally divided into three classes according to the stage of PBC： early stage, cirrhotic stage, and poor biochemical response stage. Patients in each class were equally divided into three groups according to the dose of UD- CA： 8 - 10, 13 - 15, and 20 -25 mg·kg^-1·d^-1. The general information, clinical symptoms, biochemical indices, and changes in T lymphocyte subsets and cytokines in peripheral blood after the treatment with different doses of UDCA were analyzed. Comparison of continuous data was performed by t test, and comparison of categorical data was performed by）（2 test. Results In patients with early - stage PBC who were treated with 13- 15 mg·kg^-1·d^-1 UDCA, the percentage of CD3 ＋ CD4＋ T cells, CD4 ＋/CD8 ＋ ratio, and expression of interferongamma were significantly reduced after treatment （54.8% ± 11.6% vs 34.7% ± 7.7 %, t = 6. 5, P 〈 0, 05 ; 2.3 ±1.0 vs 1.6 ± 0.6, t = 2. 7, P 〈 0.05 ; 33.0 ±12.3 vs 23.7 ± 7.2 ng/L, t = 2.9, P 〈 0.05 ）, while the secretion of interleukin - 4 was significantly increased after treatment （29.0 ± 4.6 vs 38.5 ± 7.1 ng/L, t = 5.0, P 〈 0.05 ）. Conclusion The UDCA with a dose of 13 - 15 mg·kg^-1·d^-1 can substantially improve the immune status in patients with early - stage PBC. The application of UDCA should be standardized in order to achieve the desired response.