多烯磷脂酰胆碱治疗抗结核药物所致肝损伤患者疗效研究

doi:10.3969/j.issn.1672-5069.2021.02.020

摘要/Abstract

摘要： 目的探讨多烯磷脂酰胆碱治疗抗结核药物所致肝损伤患者的疗效及对血清血红素加氧酶(HO-1)、谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)水平的影响。方法 2018年3月~2019年3月我院消化内科诊治的78例肺结核患者在抗结核药物治疗过程中发生肝损伤,采用随机数字表法将所选患者分为对照组39例和观察组39例,在抗涝治疗过程中分别给予甘草酸二铵胶囊或者多烯磷脂胆碱胶囊口服治疗,两组均连续观察12周。采用ELISA法检测血清白细胞介素-6(IL-6)、IL-1β和肿瘤坏死因子-ɑ(TNF-ɑ)水平,采用放射免疫法测定血清HO-1、GSH-Px和SOD水平。结果在观察结束时,观察组血清丙氨酸氨基转移酶(ALT)水平为(28.1±20.5)U/L,显著低于对照组【(59.4±22.7)U/L,P<0.05】,血清天冬氨酸氨基转移酶(AST)水平为(345.1±17.3)U/L,显著低于对照组【(45.1±17.3)U/L,P<0.05】;血清TNF-ɑ水平为(7.4±1.5)pg/mL,显著低于对照组【(10.3±1.8)pg/mL,P<0.05】,血清IL-1β水平为(13.7±2.1)ng/mL,显著低于对照组【(34.2±4.8)ng/mL,P<0.05】;血清HO-1水平为(294.1±16.9)U/L,显著高于对照组【(198.8±17.2)U/L,P<0.05】,血清SOD水平为(544.2±13.3)U/L,显著高于对照组【(421.0±12.8)U/L,P<0.05】。结论应用多烯磷脂酰胆碱治疗抗结核药物所致的肝损伤患者可明显升高血清HO-1和SOD水平,减轻氧化应激反应,可能与疗效较好有关,值得进一步研究。

关键词: 药物性肝损伤, 多烯磷脂酰胆碱, 甘草酸二铵, 血红素加氧酶, 超氧化物歧化酶, 治疗

Abstract: Objective To investigate the therapeutic efficacy of polyene phosphatidylcholine in patients with anti-tuberculosis agents-induced liver injury and its effect on serum heme oxygenase (HO-1), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels. Methods 78 patients drug-induced liver injury (DILI) during anti-tuberculosis therapy for pulmonary tuberculosis were enrolled in our hospital between March 2018 and March 2019, and were randomly divided into control and observation group with 39 in each, receiving diammonium glycyrrhizinate or polyene phosphatidylcholine orally for 12 weeks. Serum interleukin-6, IL-1β and tumor necrosis factor-α(TNF-ɑ) as well as serum HO-1, GSH-Px and SOD levels were detected.Results At the end of 12 week observation, serum level of alanine aminotransferase (ALT) in the observation group was (28.1 ± 20.5) U/L, which was significantly lower than that in the control group [(59.4 ± 22.7) U/L, P <0.05], and serum level of aspartate aminotransferase (AST) in the observation group was (345.1 ± 17.3) U/L, which was significantly lower than that in the control group [(45.1 ± 17.3) U/L, P <0.05]; serum TNF-ɑ level inthe observation group was (7.4 ± 1.5) pg/mL, which was significantly lower than that in the control group [(10.3 ± 1.8) pg/mL, P <0.05], and serum IL-1β level in the observation group was (13.7 ± 2.1) ng/mL, which was significantly lower than that in the control group [(34.2 ± 4.8) ng / mL, P <0.05]; serum HO-1 level in the observation group was (294.1 ± 16.9) U/L, which was significantly higher than that in the control group [(198.8 ± 17.2) U/L, P <0.05], and serum level of SOD was (544.2 ± 13.3) U/L, which was significantly higher than that in the control group [(421.0 ± 12.8) U/L, P <0.05]. Conclusion The administration of polyene phosphatidylcholine in the treatment of patients with DILI caused by anti-tuberculosis medicine is efficacious, which could significantly increase serum HO-1 and SOD levels, and reduce oxidative stress response, and needs further clinical investigation.

Key words: Drug-induced liver injury, Anti-tuberculosis drugs, Polyene phosphatidylcholine, Diammonium glycyrrhizinate, Heme oxygenase, Glutathione peroxidase, Superoxide dismutase, Therapy

刘云华, 笪荣峰, 徐湖波, 江应平, 谢华平. 多烯磷脂酰胆碱治疗抗结核药物所致肝损伤患者疗效研究[J]. 实用肝脏病杂志, 2021, 24(2): 228-231.

Liu Yunhua, Da Rongfeng, Xu Hubo, et al. Therapeutic efficacy of polyene phosphatidylcholine in patients with anti-tuberculosis agents-induced liver injury[J]. Journal of Practical Hepatology, 2021, 24(2): 228-231.

参考文献

[1] 李奎, 冉仁玉, 江自成, 等. 恩替卡韦治疗肺结核合并HBV携带者抗结核药物所致肝损伤临床初步研究. 实用肝脏病杂志, 2017, 20(5): 606-607.
[2] Yuliwulandari R, Susilowati R W, Wicaksono B D, et al. Nat2 variants are associated with drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis. J Hum Genet, 2016, 61(6): 533-537.
[3] Fang Y, Xiao H, Tang S, et al. Clinical features and treatment of drug fever caused by anti-tuberculosis drugs. Clin Respir J, 2016, 10(4): 449-454.
[4] Zhang M, Wu S Q, He J Q. Are genetic variations in glutathione s-transferases involved in anti-tuberculosis drug-induced liver injury a meta-analysis. J Clin Pharm Ther, 2019, 44(6): 844-857.
[5] Jiménez-Arellanes MA, Gutiérrez-Rebolledo GA, Meckes-Fischer M, et al. Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: a review. Asian Pac J Trop Med, 2016, 9(12): 1141-1149.
[6] 中华医学会结核病学分会. 抗结核药物性肝损伤诊治指南(2019年版). 中华结核和呼吸杂志, 2019, 10(5): 343-356.
[7] Zhao H, Wang Y, Zhang T, et al. Drug-Induced liver injury from anti-tuberculosis treatment: a retrospective cohort study. Med Sci Monit, 2020, 26(1): 920-923.
[8] 吴秀欣, 张惠勇, 张凯. 抗结核药物所致肝损伤患者血浆MiRNA-4284水平及其临床意义探讨. 实用肝脏病杂志, 2019, 22(2): 212-215.
[9] Saito Z, Kaneko Y, Kinoshita A, et al. Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis. BMC Infect Dis, 2016, 16(1): 668-669.
[10] Zazuli Z, Barliana M I, Mulyani U A, et al. Polymorphism of pxr gene associated with the increased risk of drug-induced liver injury in indonesian pulmonary tuberculosis patients. J Clin Pharm Ther, 2015, 40(6): 680-684.
[11] Shang P, Xia Y, Liu F, et al. Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (atli) in China. PLoS One, 2016, 6(7):218-219.
[12] Saito N, Yoshii Y, Kaneko Y, et al. Impact of renal function-based anti-tuberculosis drug dosage adjustment on efficacy and safety outcomes in pulmonary tuberculosis complicated with chronic kidney disease. BMC Infect Dis, 2019, 19(1): 374-375.
[13] Bhilare N V, Dhaneshwar S S, Mahadik K R, et al. Phenolic acid-tethered isoniazid for abrogation of drug-induced hepatotoxicity: design, synthesis, kinetics and pharmacological evaluation. Drug Deliv Transl Res, 2018, 8(3): 770-779.
[14] 魏明禄, 刘建民, 陈南清, 等. 滋肾益肝方联合多烯磷脂酰胆碱治疗抗结核药物所致急性肝损伤的有效性与安全性研究. 中华中医药学刊, 2018, 36(1): 45-48.
[15] Gafar F, Arifin H, Jurnalis Y D, et al. Antituberculosis drug-induced liver injury in children: incidence and risk factors during the two-month intensive phase of therapy. Pediatr Infect Dis J, 2019, 38(1): 50-53.
[16] 孙勤, 肖和平. 抗结核药物所致肝损伤分子遗传机制的探讨. 中华结核和呼吸杂志, 2018, 41(1): 10-13.
[17] Ngouleun W, Biapa Nya P C, Pieme A C, et al. Risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/aids-coinfected patients under tuberculosis treatment. Int J Mycobacteriol, 2016, 5(4): 482-488.
[18] Wu ZR, Bai ZT, Sun Y, et al. Protective effects of the bioactive natural product n-trans-caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin. Bioorg Med Chem Lett, 2015 , 25(22): 5424-5246.
[19] Njuguna C, Stewart A, Mouton J P, et al. Adverse drug reactions reported to a national HIV & tuberculosis health care worker hotline in south africa: description and prospective follow-up of reports. Drug Saf, 2016, 39(2): 159-69.
[20] Ji G, Huang W, He J, et al. Is anti-tuberculosis drug-induced hepatotoxicity due to a change in pharmacokinetics caused byalterations in antioxidant gene expression and polymorphisms in the nfe2l2 gene. Int J Clin Pharmacol Ther, 2020, 58(2): 67-73.
[21] 魏重操, 刘娜, 邢欣, 等. 多烯磷脂酰胆碱联合二甲双胍治疗非酒精性脂肪性肝病患者疗效和安全性Meta分析. 实用肝脏病杂志, 2020, 23(1): 46-49.
[22] Zhang H, Jiang T, Yu H, et al. Polyene phosphatidylcholine protects against radiation induced tissue injury without affecting radiotherapeutic efficacy in lung cancer. Am J Cancer Res, 2019, 9(6): 1091-1103.