Combination Activity of Standard Antituberculosis Drugs and Extracts of Medicinal Plants Commonly Used in Traditional Treatment of Tuberculosis in Uganda

Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.

Propolis modulates cellular biochemistry, antioxidants, cytokine profile, histological and ultra-morphological status against antituberculosis drugs induced hepatic injury

To evaluate hepatic injury induced by antituberculosis drugs(ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis(bee hive product) against ATDs induced hepatic injury. Methods: The ATDs were administered for 8 weeks as well as propolis extract at three different doses(100, 200, 400 mg/kg) conjointly for 8 weeks in rats. Silymarin(50 mg/kg) was given as positive control. Animals were euthanized after 8 weeks; blood and liver samples were collected to perform various biochemicals, serological and histopathological and ultramorphological studies. Results: Significant increase(P < 0.05) in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglyceride and cholesterol along with reduction in glucose and albumin level were noted after ATDs induced hepatic injury. Significant increase(P < 0.05) in lipid peroxidation, triglyceride, cholesterol and CYP2E1 activity; decline in reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glucose-6-phosphatase dehydrogenase activity were observed after ATDs intoxication. Due to presence of a wide range of flavonoids and polyphenols in propolis extract, its administration reduced hepatic injury and maintained biochemical indices towards control. Histopathological and electron microscopic observations indicated hepatoprotective potential of propolis at cellular level whereas, TNF-α, IL-6 and IGF-1 confirmed therapeutic potential of propolis at molecular level. Conclusions: It can be concluded that propolis possess hepatoprotective potential against ATDs induced hepatic injury that may prove itself as a clinically useful natural product in management of drug induced liver injury.

Synergistic Effects of 18β-glycyrrhetinic Acid Combined with Antituberculosis Drugs against Mycobacterium tuberculosis

The in vitro antibacterial activities of 18β-glycyrrhetinic acid alone or combined with first-line antituberculosis drugs including isoniazid（INH）,rifampicin（RFP） and streptomycin（SM） against Mycobacterium tuberculosis were detected using MABA method.The minimum inhibitory concentrations（MICs） of18β-glycyrrhetinic acid against M.tuberculosis H37Rv（ATCC 27294） and M.bovis（ATCC 19210） were 50 and 100 μg/m L,respectively.The MICs of two clinical drug-susceptible isolates and six drug-resistant isolates were 25-50 and 100-200 μg/m L,respectively.As 18β-glycyrrhetinic acid combined with INH,RFP and SM,they exhibited synergistic effects against six drug-resistant isolates,and MICs decreased significantly：MIC of INH decreased by 2-32 folds（FICIs 0.125-0.375）;MIC of RFP decreased by 4-8 folds（FICIs 0.240-0.490）;MIC of SM decreased by 4-16 folds（FICIs 0.165-0.460）.Traditional medicine monomer had low cytotoxicity on normal cell BHK-21 and could restraint SMMC fission.The results showed that 18β-glycyrrhetinic acid combined with anti-TB drugs（INH,RFP and SM） had good antibacterial activity against M.tuberculosis.These findings indicated that 18β-glycyrrhetinic acid might serve as the potential therapeutic compound for future development of anti-TB drugs.

Antituberculosis Drug-Induced Liver Injury: An Ignored Fact, Assessment of Frequency, Patterns, Severity and Risk Factors

Background/Aims: Antituberculosis drug-induced liver injury (TB DILI) is a frequent medical problem in Pakistan. Critical understanding of various aspects of TB DILI is not only important to manage liver injury but may also prevent unnecessary discontinuation of antituberculosis treatment. The study is aimed to determine the frequency, types, severity and patterns of TB DILI. Study further evaluates various risk factors of TB DILI. Materials and Methods: This is a prospective cohort study of two seventy-eight patients with the diagnosis of tuberculosis, where patients were followed during tuberculosis treatment. TB DILI was defined in accordance to international DILI expert working group. Results: Out of two seventy eight-patients, ninety-five (34.14%) had TB DILI. The most common pattern of TB DILI was hepatocellular (63.15%) followed by mixed (23.15%) and Cholestatic (13.68%). Most of the patients had mild DILI (43.15%) followed by moderate (30.52%), severe (20.01%) and very severe (5.26%). Age > 35 years, concomitant hepatotoxic drugs, extrapulmonary TB and malnutrition are important risk factors for TB DILI. Conclusion: All patterns of TB DILI with varying severity were present. Age > 35 years, malnutrition, extrapulmonary TB and concomitant use of hepatotoxic drugs were risk factors for TB DILI.

Ameliorative effect of Pergularia daemia(Forssk.) Chiov. leaves extract against anti-tuberculosis drugs induced liver injury in rats

Objective:To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia(P.daemia) against anti-tuberculosis drugs(ATDs) induced liver injury.Methods:Wistar albino rats were divided into seven groups of six animal in each.The ATDs and P.daemia extract(100,200 and 400 mg/kg,p.o.) were conjointly administered for 8 weeks and various biochemical,histoarchitectural,ultrastructural studies were performed.Results:Administration of ATDs significantly increased aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,triglycerides,cholesterol,bilirubin and decreased glucose and albumin level.Increased lipid peroxidation and reduction in glutathione,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase and glucose-6-phosphate dehydrogenase were found after ATDs exposure.Administration of P.daemia extract maintained serum biochemical indices as well as antioxidant status similar to control and diminished oxidative stress in dose dependent manner.Histological and ultra-structural observations substantiated biochemical findings.Conclusions:P.daemia has therapeutic potential against ATDs induced liver injury and may be of clinical significance after extensive studies.

苦黄注射液预防抗结核药物导致的药物性肝损伤患者疗效研究

目的本研究观察了应用苦黄注射液预防抗结核药物诱发药物性肝损伤(DILI)的作用,以避免不合理的抗痨中断治疗。方法2022年3月~2022年11月我院收治的97例肺结核患者,被随机分为试验组50例和对照组47例。所有患者均接受标准的2HREZ/4HR抗结核治疗,试验组在此治疗的基础上加用苦黄注射液治疗8周。采用ELISA法检测血清白介素6(IL-6)和肿瘤坏死因子-α(TNF-α),采用放射免疫法检测血清血红素加氧酶(HO-1)和超氧化物歧化酶(SOD)水平。结果在治疗4周末,试验适应性肝损伤和DILI发生率分别为6.0%和2.0%,显著低于对照组的17.0%和8.5%(P<0.05),在治疗8周末,试验组适应性肝损伤和DILI发生率分别为6.0%和4.0%,显著低于对照组的21.3%和17.0%(P<0.05);在治疗8周末,试验组血清ALT、AST和TBIL水平分别为(28.4±23.4)U/L、(30.8±18.7)U/L和(12.9±7.3)μmol/L,显著低于对照组【分别为(53.1±33.1)U/L、(52.5±37.7)U/L和(20.1±10.9)μmol/L,P<0.05】;试验组血清HO-1和SOD水平分别为(200.3±14.0)U/L和(418.0±18.7)U/L,显著高于对照组【分别为(128.8±21.4)U/L和(318.0±15.1)U/L,P<0.05】,而血清IL-6和TNF-α水平分别为(11.4±1.9)ng/L和(9.3±1.8)ng/L,显著低于对照组【分别为(17.5±4.0)ng/L和(14.5±3.0)ng/L,P<0.05】。结论在抗痨开始时应用苦黄能够显著降低DILI的发生,尽可能地维持标准化抗结核治疗,且安全性良好。

某院120例抗结核药物不良反应分析

目的了解某院抗结核药物不良反应(ADR)的发生特点和规律,为临床治疗提供参考,减少ADR的发生。方法从性别、年龄、给药途径、主要药物、ADR涉及的器官或系统及临床表现情况等角度对某院上报的120例抗结核药物ADR患者临床资料进行评价分析。结果在120例ADR患者中,男性占比61.67%,50岁以上患者发生ADR的比例达到了58.33%;静脉给药方式引起ADR占比达到了62.50%;严重程度一般的ADR占87.50%,新的一般的ADR占10.83%,严重的和新的严重的ADR各占0.83%;ADR累及器官或系统最多的为皮肤及其附件、消化系统、全身性反应,引起ADR最多的药物为利福平和莫西沙星。结论临床治疗中从预防、治疗、预后全过程保障患者生命安全;及时补充完善用药风险提示;医护人员加强ADR监测和上报。

水飞蓟宾胶囊与双环醇片对60岁以上抗结核患者药物性肝损伤预防效果

目的 观察60岁以上初治结核病患者预防性保肝对降低药物性肝损伤(DILI)价值,进一步比较双环醇片与水飞蓟宾胶囊的保肝效果。方法 选取青岛市胸科医院2018年2月~2023年10月收治的186例结核病患者,均行强化治疗,对照组不给予保肝药,A组给予水飞蓟宾胶囊,B组给予双环醇片。比较3组患者治疗2、4和8周后DILI发生率。并于治疗前及治疗2、4和8周后检测3组患者超氧化物歧化酶(SOD)、血清谷胱甘肽过氧化物酶(GSH-Px)水平变化。比较3组患者不良反应发生率。结果 治疗第2和4周时,DILI发生率A组为6.34%、11.11%,B组为1.58%、9.52%,均低于对照组的11.11%、23.8%,其中B组与对照组比较差异有统计学意义(χ^(2)=4.805、4.628,P<0.05)。治疗第8周时,A组、B组DILI发生率12.69%、14.28%,均低于对照组的28.57%,差异有统计学意义(χ^(2)=4.846、3.818,P<0.05)。治疗2、4和8周3个时点B组SOD水平(338.59±36.25)U/L、(342.68±25.62)U/L、(345.28±37.36)U/L高于A组(228.06±23.83)U/L、(239.98±19.58)U/L、(246.25±28.73)U/L和对照组(217.69±15.66)U/L、(205.92±29.64)U/L、(226.34±28.51)U/L,且A组高于对照组,差异有统计学意义(F=2.187、2.664、2.823,P<0.05)。治疗2和4周时B组的GSH-Px水平(88.78±9.47)U/ml、(94.56±10.09)U/ml,较A组(80.66±6.26)U/ml、(88.89±9.35)U/ml和对照组(82.23±8.44)U/ml、(86.65±7.39)U/ml高,差异有统计学意义(t=5.677、3.271、4.098、5.019,P<0.05)。除DILI外,3组不良反应发生率分别为9.52%、12.69%、11.11%,差异无统计学意义(P> 0.05)。结论 对于60岁以上初治结核患者,可考虑给予预防性保肝治疗。水飞蓟宾胶囊与双环醇片均可降低DILI发生率,相较而言双环醇片起效更快。

左氧氟沙星联合抗结核药物对肺结核痰菌转阴的效果

目的探讨左氧氟沙星联合抗结核药物对肺结核患者痰菌转阴的效果。方法收集2020年6月至2021年6月在本院就诊的肺结核患者46例为研究对象,采用随机数字表法分组,即对照组、观察组,均23例。对照组常规抗结核药物治疗,即异烟肼、利福平、乙胺丁醇和吡嗪酰胺,疗程24周。观察组在常规抗结核药物治疗基础上增加左氧氟沙星,疗程20周。统计两组患者痰菌阴转率、病灶吸收率。结果观察组治疗后痰菌阴转率86.96%高于对照组(χ^(2)=8.013,P=0.005)。观察组治疗后病灶吸收率95.65%高于对照组(χ^(2)=4.213,P=0.040)。两组均无复发。结论左氧氟沙星联合抗结核药物治疗肺结核患者,可缓解患者临床症状。

探讨益肝灵联合甘草酸二铵治疗抗结核药物性肝损伤的疗效

目的 探讨益肝灵联合甘草酸二铵治疗抗结核药物性肝损伤(ATB-DILI)的疗效,并分析其对肝功能、炎性因子水平、免疫功能的影响。方法 选取2021年6月至2023年6月鹿邑县疾病预防控制中心收治的80例ATB-DILI患者为研究对象,随机分为单一组40例、联合组40例。单一组予以甘草酸二铵治疗,联合组予以益肝灵联合甘草酸二铵治疗。统计对比两组临床疗效、不良反应、临床症状积分及治疗前后肝功能[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、γ-谷氨酰转肽酶(γ-GT)]、炎性因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)]、外周血T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+))水平变化。结果 联合组治疗有效率高于单一组,差异有统计学意义(P <0.05);治疗后,联合组临床症状积分低于单一组,差异有统计学意义(P <0.05);治疗后,联合组血清ALT、AST、TBIL、γ-GT、IL-6、TNF-α、IL-1β水平低于单一组,差异均有统计学意义(P <0.05);治疗后,联合组CD3^(+)、CD4^(+)高于单一组,CD8^(+)低于单一组,差异均有统计学意义(P <0.05);联合组不良反应发生率与单一组比较差异无统计学意义(P> 0.05)。结论 益肝灵联合甘草酸二铵治疗ATB-DILI的疗效确切且具有一定安全性,可改善临床症状,促进免疫功能、肝功能恢复,抑制炎性反应。

抗结核药物联合胸腺五肽治疗复治涂阳肺结核的效果分析

目的:分析抗结核药物联合胸腺五肽治疗复治涂阳肺结核的效果。方法:选取2021年2月—2022年2月昆明市第三人民医院收治的84例复治涂阳肺结核患者作为研究对象,随机分为对照组与试验组,各42例。对照组接受抗结核药物治疗,采用3HRZE/6HRE给药方案,试验组在对照组基础上应用胸腺五肽治疗。比较两组治疗效果。结果:试验组痰菌转阴率、病灶吸收率、空洞闭合率均高于对照组,差异有统计学意义(P<0.05)。治疗后,两组CD8+水平低于治疗前,且试验组低于对照组,两组CD4+、CD4+/CD8+水平高于治疗前,且试验组高于对照组,差异有统计学意义(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P=0.101)。结论:抗结核药物联合胸腺五肽治疗复治涂阳肺结核的效果较好,能够增强机体免疫功能,且安全性好,值得应用并予以推广。

The production and sales of antituberculosis drugs in China

Background:Tuberculosis(TB)is a major infectious disease globally.Adequate and proper use of anti-TB drugs is essential for TB control.This study aims to study China’s production capacity and sales situation of anti-TB drugs,and to further discuss the potential for China to contribute to global TB control.Methods:The production data of anti-TB drugs in China from 2011 to 2013 and the sales data from 2010 to 2014 were extracted from Ministry of Industry and Information Technology database of China and IMS Health database,respectively.The number of drugs was standardized to the molecular level of the key components before calculating.All data were described and analyzed by Microsoft Excel.Results:First-line drugs were the majority in both sales(89.5%)and production(92.3%)of anti-TB drugs in China.The production of rifampicin held the majority share in active pharmaceutical ingredients(APIs)and finished products,whilst ethambutol and pyrazinamide were the top two sales in finished products.Fixed-dose combinations only held small percentages in total production and sales weight,though a slight increase was observed.The production and sales of streptomycin showed a tendency of decrease after 2012.The trends and proportion of different anti-TB drugs were similar in production and sales,however,the production weight was much larger than that of sales,especially for rifampicin and isoniazid.Conclusions:First-line drugs were the predominant medicine produced and used in China.While the low production and sales of the second-line TB drugs and FDCs rose concerns for the treatment of multiple drug resistant TB.The redundant production amount,as well as the prompt influence of national policy on drug production and sales,indicated the potential for China to better contribute to global TB control.

New antituberculosis drugs targeting the respiratory chain

With the emergence of multidrug-resistant tuberculosis and extensive drug-resistant tuberculosis strains,there is an urgent need to develop novel drugs for the treatment of tuberculosis.The respiratory chain is a promising target for the development of newantimycobacterial agents,and a growing number of compounds have been reported and some have entered clinical trials.In this review,we summarize the main features and the electron transfer process of the mycobacterial respiratory chain,and the recent progress in the search for new small molecule inhibitors to rgeting the three main potential targets in the respiratory chain of Mycrobacterium tuberculosis.Our emphasis is on the optimization strategy of QcrB inhibitors and the challenges of developing QcrB inhibitors as antituberculosis drugs due to the alternate bd-type oxidase oxidative compensation pathway are discussed.

警惕抗结核药物引起血液系统的异常

目的 观察抗结核药物对血液系统的影响。方法 回顾性分析 1996年 1月— 2 0 0 4年 1月抗结核治疗中发生血液系统异常改变的 115例的临床资料。结果 4 812例结核病人抗结核治疗中发生血液系统异常改变 115例 (2 .4 % ) ,以白细胞减少最常见 (44 .4 % ) ,其次是全血细胞减少(2 2 .6 % )及白细胞合并血小板减少 (10 .4 % )。罕见有再生障碍性贫血、溶血性贫血、继发性骨髓纤维化。结论 几乎所有抗结核药物均可引起血液系统异常 ,以利福霉素类引起最常见 ,其次为吡嗪酰胺、异烟肼。既可引起血液系统中的一种有形成分改变 ,又可引起全血系统的异常 ,严重者引起死亡 ,应引起警惕。

抗结核药物不良反应管理的国内外指南综述分析

目的:了解国内外相关指南对抗结核药物不良反应管理的推荐意见。方法:检索国内外中英文抗结核指南,总结抗结核药物不良反应的发生规律及防治措施。结果:抗结核药物常见不良反应有胃肠反应、皮疹、肝炎等,19份指南详细阐述了各类不良反应的发生规律及其管理。结论:多份指南推荐了抗结核药物不良反应管理的权威意见,可供医师药师参考。

涂阳肺结核患者抗结核药物不良反应发生影响因素分析

目的探讨涂阳肺结核患者接受抗结核药物治疗的不良反应发生情况及其影响因素,为制定结核病防治策略提供参考。方法选择2008—2010年我国8个省（市、自治区）结核病定点医疗机构治疗诊治的涂阳肺结核患者共2 142例,根据是否发生不良反应将其分为两组,运用卡方检验单因素及logistic多因素回归对不良反应发生的危险因素进行分析。结果2 142例涂阳肺结核患者中536例患者出现不良反应,不良反应发生率为25.0%。经单因素分析结果表明年龄（χ2=23.815,P〈0.001）、吸烟情况（χ2=12.040,P=0.024）及结果差异均有统计学意义。多因素非条件logistic回归结果显示,45~64岁和≥65岁年龄组及吸烟是不良反应发生的独立危险因素,OR（95%CI）值分别为1.524（1.159~2.422）和1.756（1.200~2.570）及1.620（1.194~2.198）。结论涂阳肺结核患者中吸烟及中老年人是发生不良反应的危险因素,在患者诊治过程中,应及时对这类高危人群进行监测和主动干预,对发现和降低不良反应的发生率有着重要意义。

90例抗结核药物不良反应调查

目的：探讨抗结核药物不良反应发生的特点、分布及导致发生的相关危险因素，为临床合理用药提供参考。方法： 查取2012年 2～5月我院肺科医院全部出院病例1 000例，对使用了主要抗结核药物（异烟肼、利福平、乙胺丁醇、吡嗪酰胺）所致不良反应的发生时间、病例的年龄和性别、不良反应累及的系统 器官等进行统计，并分析不同药物所致不良反应的特点以及影响因素。结果：导致药物不良反应病例 90 例，男 56 例，女 34例，出现不良反应时间最短的为1 h，最迟的为31 d；抗结核药的不良反应主要累及泌尿、肝胆、神经、皮肤及其附件、消化、血液等 8个系统，多发不良反应包括高尿酸血症、药物肝炎、药物性皮炎等。结论：临床应重视规范治疗结核病，减小药物不良反应的发生和治疗失败，提高用药安全性，促进合理用药。

黄芩苷对抗结核药物肝损伤保护作用的实验研究

目的探讨黄芩苷对抗结核药物肝损伤的保护作用机制。方法将60只小鼠完全随机分为6组,即正常对照组,肝损伤(异烟肼+利福霉素钠)组,联苯双酯组及黄芩苷高、中、低剂量组。给药8d后,分别用光镜和电镜观察肝脏组织细胞病理学的改变情况,用免疫组织化学染色技术分析肿瘤坏死因子-α(TNF-α)的表达情况。结果黄芩苷能明显减轻肝细胞变性和坏死,炎症活动程度明显减轻(P<0.05或P<0.01);TNF-α蛋白在黄芩苷组小鼠肝脏组织内为弱阳性表达(P<0.05或P<0.01);黄芩苷3个剂量组间小鼠肝脏病理形态学及肝脏组织内TNF-α蛋白的表达均无显著性差异(P>0.05)。结论黄芩苷对抗结核药物肝损伤的保护作用可能与抑制TNF-α蛋白表达有关。

异烟肼介入凝胶体外抗结核作用及安全性评价

目的 :观察异烟肼凝胶体外抗结核活性和支气管介入的安全性。方法 :手工法、仪器法分别测定异烟肼、异烟肼凝胶的最小抑菌浓度和最小杀菌浓度及家兔经支气管介入的安全性。结果 :异烟肼凝胶对H37RV标准株、牛型结核分枝杆菌MIC值均为 1mg·L- 1 ,对草分枝杆菌MIC值为 8mg·L- 1 ,对H37RV标准株、牛型结核分枝杆菌MBC值均为 4mg·L- 1 ,对草分枝杆菌MBC值为 1 6mg·L- 1 ,异烟肼凝胶与异烟肼单体MIC、MBC值差异无显著性 ;动物安全性试验阴性。结论 :异烟肼凝胶具有与异烟肼单体相同的抗结核菌药效 ,卡波姆基质不影响异烟肼的抗菌活性 ;卡波姆基质异烟肼凝胶应用安全。

抗氧化剂预防抗结核药物致肝损伤的随机开放研究

目的探讨N-乙酰半胱氨酸(NAC)预防抗结核药物肝损伤作用。方法肺结核患者196例,2HRZE/4HR+NAC(A组)及2HRZE/4HR+双环醇(B组)为观察组,2HRZE/4HR为对照组(C组),观察8周内肝损伤情况。结果(1)A组肝损伤率17.19%,停药率45.5%,低于C组22.73%,53.3%(P=0.691,P=0.430)。B组肝损伤率19.7%,低于C组22.73%(P=0.670),B组停药率76.9%,高于C组53.3%(P=0.778)。A组患者肝损伤率及停药率低于B组(P=0.712,P=0.245)。(2)发生肝损伤时间,A组多见于4~8周,B组多见2周内,C组3个时间段内相同。(3)各组转氨酶高值时间,A组(27.67±23.047)d较B组(19.75±16.080)d及C组(19.93±14.969)d迟。肝功能恢复时间,A组(16.83±9.998)d及C组(16.14±6.982)d较B组(22.10±19.319)d短,(P=0.469,P=0.478)。结论 NAC预防性护肝作用与双环醇相似,但减少治疗中断率及延迟肝损伤发生时间,肝功能恢复时间短。