雷公藤多甙片联合异甘草酸镁治疗自身免疫性肝炎患者疗效初步研究

doi:10.3969/j.issn.1672-5069.2019.03.014

摘要/Abstract

摘要： 目的探讨应用雷公藤多甙片联合异甘草酸镁治疗自身免疫性肝炎（AIH）患者的疗效。方法 2016年6~2018年2月我院肝病科治疗的70例AIH患者被随机分成联合组和对照组,每组35例。在常规泼尼松治疗的基础上,给予对照组异甘草酸镁和给予联合组雷公藤多甙片联合异甘草酸镁治疗6个月。采用免疫浊度试验法检测血浆免疫球蛋白G（IgG）、IgA和IgM,采用干式免疫荧光定量法检测血清球蛋白（glubulin,GLO）水平,采用分光光度法检测血清透明质酸（HA）、层黏连蛋白（LN）和Ⅲ型前胶原（PCⅢ）水平。结果在治疗6月末,联合组血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）水平分别为（52.6±7.3） U/L、（45.3±7.8） U/L和（68.3±2.8） U/L,显著低于对照组【分别为（78.4±10.1） U/L、（77.2±8.9） U/L和（90.5±4.6）U/L,P<0.05】;联合组血浆IgG、IgA和IgM水平分别为（11.3±2.5） mg/mL、（2170.3±101.7） mg/mL和（2218.3±97.2）mg/mL,显著低于对照组【（14.8±2.8） mg/mL、（2857.2±108.9） mg/mL和（2919.4±113.6） mg/mL,P<0.05】;联合组血浆GLO水平为（14.6±3.9）g/L,显著低于对照组的（18.9±3.8） g/L（P<0.05）;联合组血清HA、LN和PCIII水平分别为（112.5±6.7） g/L、（60.7±4.8） g/L和（52.3±3.5） g/L,显著低于对照组【分别为（164.9±7.4） g/L、（82.8±5.6） g/L和（79.6±4.7） g/L,P<0.05】。结论雷公藤多甙片联合异甘草酸镁治疗AIH患者能够有效抑制免疫反应,减轻肝纤维化程度,改善肝功能指标。

关键词: 自身免疫性肝炎, 雷公藤多甙, 异甘草酸镁, 免疫球蛋白, 治疗

Abstract: Objection The purpose of this study was to investigate the efficacy of tripterygium glycosides combined with magnesium isoglycyrrhizinate in treatment of patients with autoimmune hepatitis（AIH）. Methods 70 patients with AIH were recruited in our hospital between June 2016 and February 2018,and were randomly divided into combined and control group,with 35 cases in each group. On the basis of routine prednisolone treatment,the patients in the control group were treated with magnesium isoglycyrrhizinate,and those in the combined group were treated with tripterygium glycyrrhizinate and magnesium isoglycyrrhizinate for six months. Methods At the end of six month treatment,serum ALT,AST and alkaline phosphatase levels in the combination treatment group were （52.6±7.3） U/L,（45.3±7.8） U/L and （68.3±2.8） U/L,significantly lower than [（78.4±10.1） U/L,（77.2±8.9） U/L and （90.5±4.6） U/L,P<0.05） in the control group;plasma immunoglobulin （IgG）,IgA,IgM and globulin levels in the combined group were （11.3±2.5） mg/mL,（2170.3±101.7） mg/mL,（2218.3±97.2） mg/mL and （14.6±3.9） g/L,significantly lower than（14.8±2.8） mg/mL,（2857.2±108.9） mg/mL,（2919.4±113.6） mg/mL and （18.9±3.8） g/L,respectively,P<0.05] in the control;serum hyaluronic acid,laminin and type III procollagen levels in the combination group were （112.5±6.7） g/L,（60.7±4.8） g/L and （52.3±3.5） g/L,which were statistically significantly lower than [（164.9±7.4） g/L,（82.8±5.6） g/L and （79.6±4.7） g/L,P<0.05] in the control group. Conclusion The application of tripterygium glycosides and magnesium isoglycyrrhizinate might effectively improve liver function tests,inhibit immune response and lighten the degree of liver fibrosis in patients with AIH.

Key words: Autoimmune hepatitis, Tripterygium glycosides, Magnesium isoglycyrrhizinate, Immunoglobulin, Therapy

周炎仪, 阳灿. 雷公藤多甙片联合异甘草酸镁治疗自身免疫性肝炎患者疗效初步研究[J]. 实用肝脏病杂志, 2019, 22(3): 365-368.

Zhou Yanyi, Yang Can. Efficacy of tripterygium glycosides combined with magnesium isoglycyrrhizinate in treatment of patients with autoimmune hepatitis[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 365-368.

参考文献

[1] Migita K,Horai Y,Kozuru H,et al.Serum cytokine profiles and Mac-2 binding protein glycosylation isomer(M2BPGi) level in patients with autoimmune hepatitis. Medicine(Baltimore),201,97(50):e13450.
[2] Zou X,Wang Y,Peng C.Magnesium isoglycyrrhizinate has hepatoprotective effects in an oxaliplatin induced model of liver injury. Int J Mol Med,2018,42(4):2020-2030.
[3] Chaouali M,Fernandes V,Ghazouani E,et al.Association of STAT4,TGFβ1,SH2B3 and PTPN22 polymorphisms with autoi-
mmune hepatitis. Exp Mol Pathol,2018,105(3):279-284.
[4] Abe K,Takahashi A,Fujita M,et al.Dysbiosis of oral microbiota and its association with salivary immunological biomarkers in autoimmune liver disease. PLoS One,2018,13(7):e0198757.
[5] Rizvi S,Gawrieh S.Autoimmune hepatitis in the elderly:diagnosis and pharmacologic management. Drugs Aging,2018,35(7):589-602.
[6] Yang Q,Wang J,Liu R,et al.Amelioration of concanavalin A-induced autoimmune hepatitis by magnesium isoglycyrrhizinate through inhibition of CD4(+)CD25(-)CD69(+) subset proliferation. Drug Des Devel Ther,2016,25(10):443-53.
[7] Qu L,Qu F,Jia Z,et al.Integrated targeted sphingolipidomics and transcriptomics reveal abnormal sphingolipid metabolism as a novel mechanism of the hepatotoxicity and nephrotoxicity of triptolide. J Ethnopharmacol,2015,170(9):28-38.
[8] 任方元,李小丹. 中西医结合治疗I型自身免疫性肝炎患者临床疗效研究. 实用肝脏病杂志,2016,19(5):549-552.
[9] Buechter M,Manka P,Heinemann FM,et al.Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients. World J Gastroenterol,2018,24(13):1410-1418.
[10] Wang W,Li X,Xu J.Magnesium isoglycyrrhizinate attenuates D-galactosamine/lipopolysaccharides induced acute liver injury of rat via regulation of the p38-MAPK and NF-kB signaling pathways. Immunopharmacol Immunotoxicol,2018,40(3):262-267.
[11] 尚瑞,吴军. 雷公藤多甙、硫唑嘌呤联合甘草酸二铵治疗自身免疫性肝炎患者初步临床研究. 实用肝脏病杂志,2017,20(3):290-293.
[12] Sun W,Wu HY,Chen S.Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding. World J Gastroenterol,2017,23(48):8500-8511.
[13] Dywicki J,Noyan F,Misslitz AC,et al.Hepatic T cell tolerance induction in an inflammatory environment. Dig Dis,2018,36(2):156-166.
[14] Tan QY,Hu Q,Zhu SN,et al.Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity via up-regulation of the Nrf2 pathway. Drug Deliv,2018,25(1):1213-1223.
[15] Wang Z,Yu C,Zhou LN,et al.Effects of tripterygium wilfordii induction therapy to IgA nephropathy patients with heavy proteinuria. Biol Pharm Bull,2017,40(11):1833-1838.
[16] Kwon RJ,Han ME,Kim JY,et al.ZHX1 promotes the proliferation,migration and invasion of cholangiocarcinoma cells. PLoS One,2016,11(11):e0165516.
[17] Hintermann E,Bayer M,Ehser J,et la. Murine junctional adhesion molecules JAM-B and JAM-C mediate endothelial and stellate cell interactions during hepatic fibrosis. Cell Adh Migr,2016,10(4):419-33.
[18] Chen F,Ma YL,Ding H,et al.Effects of tripterygium wilfordii glycosides on regulatory T cells and Th17 in an IgA nephropathy rat model. Genet Mol Res,2015,14(4):14900-14907.
[19] 张攀,刘涛,王芳芹,等. 异甘草酸镁对小鼠放射性肺纤维化的改善作用及其机制的初步研究. 中国药理学通报,2017,33(2):201-206.
[20] Ma D,Zhang J,Zhang Y,et al.Inhibition of myocardial hypertrophy by magnesium isoglycyrrhizinate through the TLR4/NF-kB signaling pathway in mice. Int Immunopharmacol,2018,55(8):237-244.