雷公藤多甙联合异甘草酸镁治疗自身免疫性肝炎患者外周血淋巴细胞PD-1和PD-L1变化

doi:10.3969/j.issn.1672-5069.2021.01.021

摘要/Abstract

摘要： 目的探讨应用雷公藤多甙联合异甘草酸镁治疗的自身免疫性肝炎(AIH)患者外周血淋巴细胞程序性死亡因子-1(PD-1)和PD-1配体(PD-L1)表达的变化。方法将76例AIH患者随机分为对照组38例和观察组38例,分别给予异甘草酸镁口服治疗或异甘草酸镁联合雷公藤多甙口服治疗,两组均治疗24周。使用CyFlow Counter流式细胞仪检测外周血T淋巴细胞PD-1/PD-L1表达,包括PD-L1⁺/CD4⁺、PD-L1⁺/CD8⁺、PD-1⁺/CD4⁺和PD-1⁺/CD8⁺表达百分比,采用ELISA法检测血清γ-干扰素(IFN-γ)。结果在治疗结束时,观察组血清谷丙转氨酶(ALT)水平为(48.9±9.7)U/L,显著低于对照组【(77.5±11.2)U/L,P<0.05】,血清谷草转氨酶(AST)水平为(45.5±7.3)U/L,显著低于对照组【(81.3±9.5)U/L,P<0.05】,血清碱性磷酸酶(ALP)水平为(65.5±2.3)U/L,显著低于对照组【(91.3±5.8)U/L,P<0.05】;外周血淋巴细胞PD-L1⁺/CD4⁺百分比为(15.4±4.5)%,显著低于对照组【(19.3±5.8)%,P<0.05】,外周血PD-L1⁺/CD8⁺为(6.5±2.7)%,显著低于对照组【(9.2±3.0)%,P<0.05】,外周血PD-1⁺/CD4⁺为(7.4±2.6)%,显著低于对照组【(12.5±3.1)%,P<0.05】,外周血PD-1⁺/CD8⁺为(7.5±1.7)%,显著低于对照组【(10.1±1.2)%,P<0.05】;血清GLO水平为(13.4±1.5)g/L,显著低于对照组【(18.3±1.8)g/L,P<0.05】,血清IgG水平为(10.9±2.4)mg/mL,显著低于对照组【(13.6±2.9)mg/mL,P<0.05】,血清IFN-γ水平为(13.0±2.4)ng/mL,显著低于对照组【(18.1±2.8)ng/mL,P<0.05】。结论应用雷公藤多甙联合异甘草酸镁治疗AIH患者近期疗效较好,可能与改善了外周血T细胞PD-1和PD-L1表达有关,值得进一步研究。

关键词: 自身免疫性肝炎, 雷公藤多甙, 异甘草酸镁, 程序性死亡因子-1, 程序性死亡因子-1配体, 治疗

Abstract: Objective To investigate the changes of peripheral blood lymphocyte programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in patients with autoimmune hepatitis (AIH) receiving tripterygium wilfordii polyglycosides and magnesium iso-glycyrrhizate. Methods 76 patients with AIH were randomly divided into control (n=38) and observation group (n=38). The patients in the control group were treated with magnesium isoglycyrrhizate, and those in the observation group were treated with tripterygium wilfordii polyglycosides and magnesium combination. The regimen lasted for 24 weeks in both groups. The expression of PD-1 and PD-L1 percentages on peripheral blood T lymphocytes were detected by CyFlow Counter flow cytometry, including PD-L1⁺/CD4⁺, PD-L1⁺/CD8⁺, PD-1⁺/CD4⁺ and PD-1⁺/CD8⁺, and serum γ-interferon (IFN-γ) was assayed by ELISA. Results At the end of 24 week treatment, serum alanine aminotransferase (ALT) level in the observation group was (48.9±9.7) U/L, significantly lower than that in the control group (77.5±11.2) U/L, P<0.05), serum aspertate aminotransferase (AST) level was (45.5±7.3) U/L, significantly lower than that in the control group ((81.3±9.5) U/L, P<0.05), and serum alkaline phosphatase (ALP) levels was (65.5±2.3) U/L, significantly lower than that inthe control group (91.3±5.8) U/L, P<0.05); the percentage of peripheral blood lymphocyte PD-L1⁺/CD4⁺ was (15.4±4.5) %, significantly lower than that in the control group , the PD-L1⁺/CD8⁺ percentage was (6.5±2.7) %, significantly lower than that in the control group , the PD-1⁺/CD4⁺ was (7.4±2.6) %, significantly lower than that in the control group , and the peripheral blood lymphocyte PD-1⁺/CD8⁺ percentage was (7.5 ± 1.7)%, significantly lower than that in the control group ; serum globulin level was (13.4±1.5) g/L, significantly lower than that in the control group [(18.3±1.8) g/L, P<0.05), serum IgG level was (10.9±2.4) mg/mL, significantly lower than that in the control group [(13.6±2.9) mg/mL, P<0.05), and serum IFN-γ level was (13.0±2.4) ng/mL, significantly lower than [(18.1±2.8) ng/mL, P<0.05) in the control group.Conclusion The combination of tripterygium wilfordii polyglycosides and magnesium iso-glycyrrhizate in treatment of patients with AIH have a short-term efficacy, which might be related to the reduction of PD-1 and PD-L1 expression on peripheral blood T lymphocytes, and restoration of immune dysfunction.

Key words: Autoimmune hepatitis, Tripterygium wilfordii polyglycoside, Magnesium iso-glycyrrhizate, Programmed death -1, Programmed death -1 ligand, Therapy

李庆玲, 何树光, 易小明, 段婷娜, 周意. 雷公藤多甙联合异甘草酸镁治疗自身免疫性肝炎患者外周血淋巴细胞PD-1和PD-L1变化[J]. 实用肝脏病杂志, 2021, 24(1): 79-82.

Li Qingling, He Shuguang, Yi Xiaoming, et al. Changes of peripheral blood lymphocyte PD-1 and PD-L1 expression in patients with autoimmune hepatitis receiving tripterygium wilfordii polyglycosides and magnesium iso-glycyrrhizate[J]. Journal of Practical Hepatology, 2021, 24(1): 79-82.

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