摘要
目的 探讨贝达喹啉联合肝爽颗粒治疗耐多药肺结核(multidrug resistant tuberculosis,MDR-TB)的应用效果及对γ 干扰素诱导蛋白10(interferon-γ inducible protein-10,IP-10)、细胞因子信号传导抑制蛋白1(suppressors of cytokine signaling,SOCS1)的影响.方法 按1:1倾向性匹配原则将2022年1月至2022年10月河北省胸科医院结核四科收治的144例MDR-TB患者分为对照1组、对照2组及联合组,各48例.3组均在予以常规治疗基础上,对照1组予以肝爽颗粒,对照2组予以贝达喹啉,联合组予以肝爽颗粒和贝达喹啉.比较3组治疗第4、8、12、24、36、48周痰菌转阴率及中位转阴时间.比较3组治疗48周后病灶吸收情况、空洞变化情况.比较3组治疗前、治疗第8、24、48周血清炎症因子[干扰素-γ(interferon-γ,IFN-γ)、白细胞介素(interleukin,Il)-4、Il-17、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、IP-10、SOCS1]水平及受试期间不良反应发生情况.结果 对照2组、联合组第4、8、12、24、36、48周痰菌转阴率均高于对照1组(P均<0.05);对照2组、联合组中位转阴时间均早于对照1组(P均<0.05);对照2组、联合组病灶吸收率分别为93.75％、95.83％,均高于对照1组56.25％(P均<0.05);对照2组、联合组空洞改善率分别为95.83％、95.83％,均高于对照1组62.50％(P均<0.05);联合组第8、24、48周IL-17、TNF-α、IL-4水平<对照2组<对照1组(P均<0.05);联合组第8、24、48周IP-10、SOCS1水平<对照2组<对照1组(P均<0.05);对照2组、联合组心电图异常率分别为16.67％、12.50％,均高于对照1组(0)％(P均<0.05);联合组肝损伤和胃肠系统不良反应发生率均为0,分别低于对照2组12.50％、16.67％ 和对照1组14.58％、14.58％(P均<0.05).结论 含贝达喹啉治疗方案能提高MDR-TB的病灶吸收率、空洞闭合率、痰菌转阴率,抑制炎症反应,联合肝爽颗粒虽未增强疗效,但能进一步改善炎症反应,减少肝损伤和胃肠道不良反应的发生,可能有助于增加患者贝达喹啉治疗的耐受性和依从性.
Abstract
Objective To investigate the therapeutic effects of bedaquinoline on multidrug resistant tuberculosis (MDR-TB) and its impact on interferon-induced protein 10 (IP-10) and suppressors of cytokine signaling 1 (SOCS1). Methods Using a 1:1 propensity matching principle,144 patients with MDR-TB admitted to the Tuberculosis Department Ⅳ of our hospital from January to October 2022 were divided into 3 groups,each with 48 patients. All 3 groups received conventional treatment,Control group 1 received Ganshuang Granules,control group 2 received bedaquiline,and the combination group received both. The sputum negative conversion rate and median negative conversion time were compared among the 3 groups at 4,8,12,24,36 and 48 weeks. Changes in lesion absorption and cavity were compared among the three groups after 48 weeks of treatment. Changes in serum inflammatory factors (IFN-γ,IL-4,IL-17,TNF-α,IP-10,and SOCS1) and adverse reactions were compared among the three groups before treatment and at 8,24 and 48 weeks post-treatment. Results Sputum bacteria in control group 2 and the combination group at weeks 4,8,12,24,36,and 48 were higher than those in control group 1 (P<0.05). Median conversion times in the control group 2 and the combined group was earlier than in the control group 1 (P<0.05). Lesion absorption rates in tcontrol group 2 and the combination group were 93.75％ and 95.83％,respectively,both higher than in the control group 1 (56.25％) (P<0.05). Cavity improvement rates in control group 2 and the combined group were 95.83％ and 95.83％,higher than in control group 1 (62.50％) (P<0.05). At weeks 8,24,and 48,the levels of IL-17,TNF-α,and IL-4 in the combination group were lower than in control group 2 and higher than in control group 1 (P<0.05). Levels of IP-10 and SOCS1 in the combination group at weeks 8,24,and 48 were lower than in control group 2,and these were lower than in control group 1 (P<0.05). Rates of electrocardiogram abnormality in control 2 group and the combination group were 16.67％ and 12.50％,respectively,higher than in control group 1 by 0 (P<0.05). Rates of liver injury and gastrointestinal adverse reactions in the combination group were 0,lower than that in control group 2 by 12.50％ and 16.67％,and control group 1 by 14.58％ and 14.58％,respectively (P<0.05). Conclusions The bedaquiline-containing regimen improves lesion absorption,cavity closure,and sputum conversion rates in MDR-TB,while inhibiting inflammatory response. Although combining with Ganshuang Granules did not enhance efficacy,it further improved the inflammatory response and reduced liver injury and gastrointestinal adverse reactions,potentially increasing patient tolerance and compliance with bedaquiline therapy.
基金项目
河北省医学科学研究课题(2023)(20231223)
维普
万方数据