双环醇片治疗抗结核药物致肝功能损害的临床研究

Clinical trial of bicyclic alcohol in the treatment of patients with liver function impairment caused by antituberculosis drugs

目的观察双环醇治疗抗结核药物所致肝损害(ATLI)的临床疗效和安全性。方法按照随机数字表法将142例初治肺结核患者分为对照组和试验组,每组71例:对照组予以2HREZ/4HR方案(前2个月:异烟肼H、利福平R、乙胺丁醇E、吡嗪酰胺Z;后4个月:异烟肼、利福平)+葡醛内酯片治疗,异烟肼片0.3 g,qd,利福平胶囊0.45~0.60 g,qd,盐酸乙胺丁醇片0.75 g,qd,吡嗪酰胺片0.75 g,qd,葡醛内酯片200 mg,tid。在对照组的基础上,试验组给予双环醇片25mg,tid。2组的总疗程均为6个月。治疗结束后,用全自动生化分析仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)等水平;用流式细胞仪检测外周血T淋巴细胞水平;用硫代巴比妥酸比色法检测血清丙二醛(MDA)水平;用黄嘌呤氧化酶法检测血清超氧化物歧化酶(SOD)水平;用二硫基双硝基苯甲酸法检测血清谷胱甘肽过氧化物酶(GSH-Px)水平,计算2组的ATLI发生率及药物不良反应(ADR)发生率。结果治疗后,试验组和对照组的ALT、AST、TBil分别为(43.16±4.53),(68.76±8.35)U·L^(-1);(39.64±5.06),(66.32±8.26)U·L^(-1);(18.05±2.19),(66.32±8.26)μmol·L^(-1),与对照组比较,差异均有统计学意义(均P<0.05)。对照组和试验组的CD3+、CD4+、CD8+分别为(61.38±7.85)%,(66.35±8.16)%;(36.93±4.06)%,(39.74±4.13)%;(35.09±3.14)%,(32.11±3.22)%;这2组的MDA分别为(7.23±1.02),(5.01±0.63)mmol·m L^(-1),这2组的SOD分别为(432.36±32.17),(497.47±35.45)U·m L^(-1),这2组的GSH-Px分别为(94.65±11.88),(115.54±12.12)U·L^(-1),与对照组相比,试验组差异均有统计学意义(均P<0.05)。对照组的ATLI发生率为16.90%,高于试验组的4.23%;试验组ADR发生率为7.05%,低于对照组的18.32%,组间比较差异均有统计学意义(均P<0.05)。结论双环醇能有效地保护肺结核患者肝功能并预防抗结核药物导致的肝功能损害,安全性较高。

Objective To investigate the clinical efficacy and safety of bicyclic alcohol in the treatment of patients with antituberculotic induced liver injury（ ATLI） caused by antituberculosis drugs. Methods Patients with pulmonary tuberculosis in our hospital were selected. Grouped by random number table, 71 cases in the control group treated with 2HREZ/ 4HR [ The first 2 months ： isonicotinyl hydrazide （ H ） ± rifampicin （R） ± ethambutol （ E ） ± pyrazinamide （Z） ; after 4 months ： isonicotinyl hydrazide ± rifampicin ] antituberculosis combined with glucurolactone tablets,isoniazid tablets 0.3 g, qd, rifampicin capsules 0. 45 - 0. 60 g, qd, ethambutol hydrochloride tablets 0. 75 g, qd, pyra- zinamide tablets 0.75 g, qd,glucurolactone tablets 200 mg, tid;71 cases in the treatment group,in the basis of control group, was given bicyclol alcohol tablets 25 mg, tid. The total course of treatment was 6 months in the two groups. After the treatment, the levels of serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, total bilirubin （TBil） and other liver function indexes were detected by automatic biochemical analyzer. The peripheral blood T lym- phocyte levels were detected by flow cytometry. The serum malondialdehyde （MDA） levels were measured by thiobarbi- turic acid colorimetric assay. The levels of serum superoxide dismutase （SOD） were detected by xanthine oxidase method. The serum glutathione peroxidase（ GSH -Px） levels were measured by two sulfur based double nitrobenzene formic acid assay. The incidence of ATLI and the incidence of adverse drugs reaction （ADR） were calculated. Results The levels of serum ALT, AST and TBil in the treatment and control groups after treatment were （43.16 ± 4.53）, （68.76±8.35）U.L-1;（39.64±5.06）,（66.32 ±8.26）U· L-1;18.05 ±2.19）,（66.32 ±8.26）p, mol· L-1. Compared with control group ,the difference had significantly（ all 19. 〈 0. 05 ）. The levels of CD3＋ , CD4＋ , CD8＋ in the control group and treatment group were （61.38 ± 7. 85 ） %, （ 66. 35 ± 8. 16 ） % ; （ 36. 93± 4. 06 ） %, （ 39. 74± 4. 13 ） % ; （35.09 ± 3.14）%, （32. 11 ± 3.22）%;the levels of MDA in the two groups were （7.23 ± 1.02 ）, （5.01 ± 0. 63 ） mmol · mL-1 ;the levels of SOD-in the two groups were （432. 36 ± 32. 17）, （497.47 ± 35.45）U· mL-1; the levels of GSH - Px in the two groups were （94. 65 ±11. 88 ）, （ 115.54 ± 12. 12） U· L-1. Compared with control group, the difference in above factors had significantly（ all P 〈 0. 05 ）. The incidence of ATLI in the control group （ 16. 90% ） was higher than that in the treatment group （4. 23% ） with significantly （P 〈 0. 05 ） ;the incidence of ADR in the treatment group （7.05%） was lower than that of the control group （18.32%） with significantly （P 〈 0. 05 ）. Conclusion Bicyclic alcohol can effectively protect the liver function of patients with pulmonary tuberculosis, and prevent the ATLI ; the safety is high.