炎症细胞因子对抗结核性药物肝损伤的预测作用
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摘要
目的探讨肺结核患者在抗结核治疗过程中炎症细胞因子对抗结核性药物肝损伤的预测作用。方法将初治肺结核患者随机分为护肝药干预组和空白对照组,用液相芯片技术检测抗结核治疗前、治疗2周后或发生药物性肝损伤时的血清中炎症细胞因子IL-4、IL-6、IL-8、IL-10、IL-1α、IL-1β、IFN-γ及肿瘤坏死因子-α(TNF-α)的变化。结果护肝药干预组及空白对照组的抗结核性药物肝损伤发生率分别为14.77%和15.56%,且两组发生药物性肝损伤时各炎症细胞因子血清浓度差异无统计学意义(P> 0.05)。在肝损伤组和非肝损伤组中,抗结核治疗后IFN-γ和IL-6的血清浓度均较治疗前明显下降,而IL-10较治疗前则明显升高,差异有统计学意义(P <0.05);炎症细胞因子IL-4仅在发生肝损伤时血清浓度下降并伴TNF-α的血清浓度升高,差异有统计学意义(P <0.05);IL-8、IL-1α和IL-1β在肝损伤组和非肝损伤组中治疗前后血清浓度均无明显变化(P> 0.05)。结论血清炎症细胞因子IL-4的降低伴TNF-α的升高对于抗结核性药物性肝损伤的发生具有预测意义。
Objective To explore the predictive role of inflammatory cytokines in hepatic injury during antituberculosis treatment.MethodsUntreated tuberculosis patients were randomly divided into liver protection drug intervention group and blank control group,and were collected the serum before treatment,treatment for 2weeks or during drug-induced liver injury.The serum levels of IL-4,IL-6,IL-8,IL-10,IL-1α,IL-1β,IFN-γand TNF-αwere detected by the liquid chip technology.ResultsLiver protection drug intervention group and blank control group of anti-tb drugs liver injury incidence were 14.77%and 15.56%respectively,and two groups of all cytokines has no difference when drug-induced liver injury occurs(P>0.05).In hepatic injury group and nonliver injury group,IFN-γand IL-6 was significantly decreased while IL-10 was significantly higher than before treatment(P<0.05).In addition,IL-4 decreased only during the occurrence of anti-tuberculous liver injury,accompanied by an increase of TNF-α,which was statistically significant(P<0.05).Other cytokines,IL-8、IL-1αand IL-1β,were not significantly changed before and after the treatment of hepatic injury group and non-hepatic injury group(P>0.05).Conclusion The decrease of IL-4 accompanied by the increase of TNF-αis of significance for the occurrence of anti-tuberculous drug-induced liver injury.
Objective To explore the predictive role of inflammatory cytokines in hepatic injury during antituberculosis treatment.MethodsUntreated tuberculosis patients were randomly divided into liver protection drug intervention group and blank control group,and were collected the serum before treatment,treatment for 2weeks or during drug-induced liver injury.The serum levels of IL-4,IL-6,IL-8,IL-10,IL-1α,IL-1β,IFN-γand TNF-αwere detected by the liquid chip technology.ResultsLiver protection drug intervention group and blank control group of anti-tb drugs liver injury incidence were 14.77%and 15.56%respectively,and two groups of all cytokines has no difference when drug-induced liver injury occurs(P>0.05).In hepatic injury group and nonliver injury group,IFN-γand IL-6 was significantly decreased while IL-10 was significantly higher than before treatment(P<0.05).In addition,IL-4 decreased only during the occurrence of anti-tuberculous liver injury,accompanied by an increase of TNF-α,which was statistically significant(P<0.05).Other cytokines,IL-8、IL-1αand IL-1β,were not significantly changed before and after the treatment of hepatic injury group and non-hepatic injury group(P>0.05).Conclusion The decrease of IL-4 accompanied by the increase of TNF-αis of significance for the occurrence of anti-tuberculous drug-induced liver injury.
引文
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[13]张国英,钮晓红,徐卫平,等.淋巴结核患者外周血CD4+CD25highFoxP3+调节性T淋巴细胞以及血浆IFN-γ和IL-10水平及其临床意义[J].检验医学,2015,30(1):31-35.
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[15]ZHANG D G,ZHANG C,WANG J X,et al.Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation[J].Toxicol Appl Pharmacol,2017,314:39-47.
[16]王莉,宋育林,何雪.PPARa激活可改善利福平合用异烟肼所致的大鼠肝损伤[J].安徽医科大学学报,2014,49(8):1057-1061.
[2]RAMOS-ESPINOSA O,ISIAS-WEINSTEIN L,PERAITA-áLVAREZ M P,et al.The use of immunotherapy for the treatment of tuberculosis[J].Expert Rev Respir Med,2018,12(5):427-440.
[3]CHANG T E,HUANG Y S,CHANG C H,et al.The susceptibility of anti-tuberculosis drug-induced liver injury and chronichepatitis C infection:A systematic review and meta-analysis[J].JChin Med Assoc,2017,81(2):111-118.
[4]PARK W B,KIM W,LEE K L,et al.Antituberculosis drug-induced liver injury in chronic hepatitis and cirrhosis[J].J Infect,2010,61(4):323-329.
[5]梅小平,敬雪明,李健,等.乙型肝炎患者血清IL-6、IL-8、TNF-α水平与肝损程度、HBV DNA含量的相关性分析[J].中国现代医学杂志,2006,16(3):395-397.
[6]BONKOVSKY H L,BARNHART H X,FOUREAU D M,et al.Cytokine profiles in acute liver injury-Results from the US DrugInduced Liver Injury Network(DILIN)and the Acute Liver Failure Study Group[J].PLoS One,2018,13(10):e0206389.
[7]TWEED C D,WILLS G H,CROOK A M,et al.Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study[J].BMC Med,2018,16(1):46.
[8]邢春娇.双环醇预防抗结核药物性肝损害临床研究[J].中国基层医药,2013(2):16-17.
[9]XU L,ZHANG F,XU C,et al.Is the Prophylactic Use of Hepatoprotectants Necessary in Anti-Tuberculosis Treatment[J]?Chemotherapy,2017,62(5):269-278.
[10]杨雪迎,李艳,李哲明,等.护肝药物预防抗结核药物所致肝损伤的作用[J].实用医学杂志,2015,31(13):2194-2196.
[11]吴怡玲,邓国防.抗结核药物性肝炎患者血清IL-10与IFN-γ水平的变化及意义[J].实用临床医学,2013,14(11):15-16,18.
[12]郝兴亮,蔺景双,崔丽华,等.γ-干扰素释放试验、细胞因子IL-6、IL-23对菌阴肺结核的诊断价值[J].中国医师杂志,2016,18(12):1878-1880.
[13]张国英,钮晓红,徐卫平,等.淋巴结核患者外周血CD4+CD25highFoxP3+调节性T淋巴细胞以及血浆IFN-γ和IL-10水平及其临床意义[J].检验医学,2015,30(1):31-35.
[14]梁晓燕.肺结核患者体内结核病相关免疫细胞因子动态变化观察[J].社区医学杂志,2016,14(14):54-55.
[15]ZHANG D G,ZHANG C,WANG J X,et al.Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation[J].Toxicol Appl Pharmacol,2017,314:39-47.
[16]王莉,宋育林,何雪.PPARa激活可改善利福平合用异烟肼所致的大鼠肝损伤[J].安徽医科大学学报,2014,49(8):1057-1061.