Study on the mechanism of N- acetylcysteine in alleviating cisplatin-induced liver injury

Yang Biqian; He Huiming; Yin Tingmei; Fu Xiaoyan; Gao Guangmiao; Yang Lingling; Li Jie; Lian Xiaolong; Deng Yi

doi:10.13406/j.cnki.cyxb.003780

您当前的位置：

首页 >

文章列表页 >

Study on the mechanism of N- acetylcysteine in alleviating cisplatin-induced liver injury

Basic research | 更新时间：2025-10-22

- Study on the mechanism of N- acetylcysteine in alleviating cisplatin-induced liver injury
- Journal of Chongqing Medical University Vol. 50, Issue 6, Pages: 815-820(2025)
- 作者机构：
  
  1.广元市中医医院药剂科，广元 628000
  2.甘肃中医药大学药学院，兰州 730000
  3.青海大学药学院，西宁 810016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003780
  CLC： R575.1
- Received：07 August 2023，
  
  Revised：2024-01-10，
  
  Accepted：18 March 2024，
  
  Published：28 June 2025
- 稿件说明：
移动端阅览
杨必乾,何慧明,殷亭湄,等.N-乙酰半胱氨酸缓解顺铂肝损伤的作用机制研究[J].重庆医科大学学报,2025,50(6):815-820.

Yang Biqian,He Huiming,Yin Tingmei,et al.Study on the mechanism of N- acetylcysteine in alleviating cisplatin-induced liver injury[J].Journal of Chongqing Medical University,2025,50(6):815-820.
杨必乾,何慧明,殷亭湄,等.N-乙酰半胱氨酸缓解顺铂肝损伤的作用机制研究[J].重庆医科大学学报,2025,50(6):815-820. DOI： 10.13406/j.cnki.cyxb.003780.

Yang Biqian,He Huiming,Yin Tingmei,et al.Study on the mechanism of N- acetylcysteine in alleviating cisplatin-induced liver injury[J].Journal of Chongqing Medical University,2025,50(6):815-820. DOI： 10.13406/j.cnki.cyxb.003780.

摘要

目的

研究N-乙酰半胱氨酸（N-acetylcysteine，NAC）对顺铂肝损伤大鼠的肝保护作用以及肠道菌群、白细胞介素6（interleukin-6，IL-6）、肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）以及核因子κB（nuclear factor-κB，NF-κB）表达的影响。

方法

雄性SD大鼠随机分为对照组（NC组）、顺铂组（CP组）和N-乙酰半胱氨酸组（NAC组）。NAC组用NAC 15 mg/kg连续灌胃8 d。第5天灌胃30 min后，除NC组外均腹腔注射8 mg/kg顺铂诱导大鼠急性肝损伤。以全自动生化分析仪检测天冬氨酸转氨酶（aspartate transaminase，AST）、丙氨酸转氨酶（alanine transaminase，ALT）、碱性磷酸酶（alkaline phosphatase，ALP）和总胆红素（total bilirubin，TBIL）的含量。计算大鼠的肝指数。用Western blot测定和分析各组大鼠肝组织中NF-κB、IL-6、TNF-α的相对表达量。利用16S rDNA技术对各样本V3-V4区扩增信息进行测定与分析。

结果

相较于NC组，CP组的AST、ALT、ALP和TBIL的含量均明显上升，而NAC的介入逆转了顺铂致大鼠肝功能异常；相较于NC组，CP组大鼠的肝指数明显升高（

=0.000），而NAC组大鼠肝指数相较于CP组明显下降（

=0.007）；相对于NC组，CP组IL-6、TNF-α和NF-κB表达都明显上升，而NAC组降低了这些基因的表达，IL-6和TNF-α表达差异有统计学意义（

=0.006，

=0.000）。相对于NC组，CP组肠道菌群的α多样性指数均明显升高，而相较于CP组，NAC组肠道菌群的α多样性指数均有下降趋势。在门水平，与CP组比较，NAC组放线菌门丰度增加而厚壁菌门的丰度减少。在属水平，与CP组比较，NAC组瘤胃球菌属的丰度下降，双歧杆菌属和异杆菌属丰度升高。

结论

NAC能够缓解顺铂急性肝损伤，其机制可能与下调IL-6、TNF-α和NF-κB的表达以及调节肠道菌群丰度及多样性有关。

Abstract

Objective

To investigate the hepatoprotective effect of N-acetylcysteine（NAC） on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6（IL-6），tumor necrosis factor-α（TNF-α），and nuclear factor-kappa B（NF-κB）.

Methods

Male Sprague-Dawley rats were randomly divided into control group（CG），cisplatin group（CP），and NAC group. The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days. At half an hour after intragastric administration on the fifth day，all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury. An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase（AST），alanine aminotransferase（ALT），alkaline phosphatase（ALP），and total bilirubin（TBIL）； liver index was calculated for the rats； Western blot was used to measure the relative expression levels of NF-κB，IL-6，and TNF-α in liver tissue； the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.

Results

Compared with the NC group，the CP group had significant increases in the content of AST，ALT，ALP，and TBIL，while NAC reversed the abnormal liver function caused by cisplatin. Compared with the NC group，the CP group had a significant increase in liver index（

=0.000），while the NAC group had a significant reduction in liver index compared with the CP group（

=0.007）. Compared with the NC group，the CP group had significant increases in the expression levels of IL-6，TNF-α，and NF-κB，while the NAC group showed reductions in the expression of these genes，with significant differences in the expression of IL-6 and TNF-α（

=0.006 and 0.000）. Compared with the NC group，the CP group had a significant increase

in the α-diversity index of intestinal flora，while compared with the CP group，the NAC group tended to have a reduction in the α-diversity index of intestinal flora. Compared with the CP group at the phylum level，the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes. Compared with the CP group at the genus level，the NAC group had a reduction in the abundance of Ruminococcaceae and increases in the abundance of Bifidobacterium and Allobaculum.

Conclusion

NAC can alleviate acute liver injury caused by cisplatin，possibly by downregulating the expression of IL-6，TNF-α，and NF-κB and regulating the abundance and diversity of intestinal flora.

关键词

Keywords

references

European Association for the Study of the Liver . EASL Clinical Practice Guidelines：drug-induced liver injury [J ] . J Hepatol ， 2019 ， 70 （ 6 ）： 1222 - 1261 ．

Chalasani NP ， Maddur H ， Russo MW ， et al . ACG clinical guideline：diagnosis and management of idiosyncratic drug-induced liver injury [J ] . Am J Gastroenterol ， 2021 ， 116 （ 5 ）： 878 - 898 ．

DuYF ， Liu JR ， Ye FX . Efficacy of N-acetylcysteine combined with bicyclic alcohol in the treatment of patients with drug-induced liver injury caused by anti-tuberculosis drugs [J ] . Journal of Practical Hepatology ， 2021 ， 24 （ 6 ）： 847 - 850 .

Moosa Muhammed S ， Gary M ， Hannah G ， et al . A randomized controlled trial of intravenous N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury [J ] . Clin Infect Dis Off Publ Infect Dis Soc Am ， 2020 ， 73 （ 9 ）： 3377 - 3383 ．

Kang KS ， Shin S ， Lee SI . N-acetylcysteine modulates cyclopho-sphamide-induced immunosuppression，liver injury，and oxidative stress in miniature pigs [J ] . J Anim Sci Technol ， 2020 ， 62 （ 3 ）： 348 - 355 ．

Eroglu N ， Erduran E ， Reis GP ， et al . Therapeutic effect of N-acetylcysteine on chemotherapy-induced liver injury [J ] . Ir J Med Sci ， 2020 ， 189 （ 4 ）： 1189 - 1194 ．

吴夏飞，连娜琦，陆春风，等 . 肠道菌群对慢性肝脏疾病影响的研究进展 [J ] . 中国药理学通报， 2013 ， 29 （ 12 ）： 1644 - 1647 ．

Wu XF ， Lian NQ ， Lu CF ， et al . Research progress on effect of intestinal flora on chronic liver diseases [J ] . Chin Pharmacol Bull ， 2013 ， 29 （ 12 ）： 1644 - 1647 ．

Gong SH ， Feng YL ， Zeng YN ， et al . Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice [J ] . J Transl Med ， 2021 ， 19 （ 1 ）： 147 ．

Man Q ， Deng Y ， Li PJ ， et al . Licorice ameliorates cisplatin-induced hepatotoxicity through antiapoptosis，antioxidative stress，anti-inflammation，and acceleration of metabolism [J ] . Front Pharmacol ， 2020 ， 11 ： 563750 ．

岑梦佳，冯　春，韩婕，等 . 不同血糖控制水平对糖尿病大鼠肝功能及形态的影响 [J ] . 中国临床药理学杂志， 2021 ， 37 （ 19 ）： 2609 - 2613 ．

Cen MJ ， Feng C ， Han J ， et al . Effects of different blood glucose levels on liver function and morphology in diabetic rats [J ] . Chin J Clin Pharmacol ， 2021 ， 37 （ 19 ）： 2609 - 2613 ．

郭　威，李三强，宋晓改，等 . L-谷氨酰胺对急性酒精肝损伤小鼠的保护作用机制研究 [J ] . 中国临床药理学杂志， 2020 ， 36 （ 13 ）： 1812 - 1814 ．

Guo W ， Li SQ ， Song XG ， et al . Protective effect and mechanism of L-glutamine on acute alcoholic liver injury in mice [J ] . Chin J Clin Pharmacol ， 2020 ， 36 （ 13 ）： 1812 - 1814 ．

Grigor’eva IN . Gallstone disease，obesity and the firmicutes/bacteroidetes ratio as a possible biomarker of gut dysbiosis [J ] . J Pers Med ， 2020 ， 11 （ 1 ）： 13 ．

Guangorena-Gómez JO ， Lozano-Ochoa II ， Rivera-Medina IL ， et al . Relationship among Blastocystis ，the firmicutes/bacteroidetes ratio and chronic stress in Mexican university students [J ] . Curr Microbiol ， 2022 ， 79 （ 3 ）： 72 ．

Björnsson HK ， Björnsson ES . Drug-induced liver injury：Pathogenesis，epidemiology，clinical features，and practical management [J ] . Eur J Intern Med ， 2022 ， 97 ： 26 - 31 ．

Eissa LA ， Kenawy HI ， El-Karef A ， et al . Antioxidant and anti-inflammatory activities of berberine attenuate hepatic fibrosis induced by thioacetamide injection in rats [J ] . Chem Biol Interact ， 2018 ， 294 ： 91 - 100 ．

Erol G ， Kartal H ， Comu FM ， et al . Effects of N-acetylcysteine and N-acetylcysteine amide on erythrocyte deformability and oxidative stress in a rat model of lower extremity ischemia-reperfusion injury [J ] . Cardiol Res Pract ， 2020 ， 2020 ： 6841835 ．

Wu GY ， Win S ， Than TA ， et al . Gut microbiota and liver injury（Ⅰ）-acute liver injury [J ] . Adv Exp Med Biol ， 2020 ， 1238 ： 23 - 37 ．

Baker SS ， Baker RD . Gut microbiota and liver injury（Ⅱ）：chronic liver injury [J ] . Adv Exp Med Biol ， 2020 ， 1238 ： 39 - 54 ．

Sun XW ， Cui Q ， Ni J ， et al . Gut microbiota mediates the therapeutic effect of monoclonal anti-TLR4 antibody on acetaminophen-induced acute liver injury in mice [J ] . Microbiol Spectr ， 2022 ， 10 （ 3 ）： e0064722 ．

李莉莉，谢瑞祺，王　莉，等 . 肝硬化患者肠道微生物与生化指标的关联性 [J ] . 生物学杂志， 2021 ， 38 （ 6 ）： 82 - 86 ．

Li LL ， Xie RQ ， Wang L ， et al . Correlation analysis between gut microbiota and biochemical indicators of cirrhosis [J ] . J Biol ， 2021 ， 38 （ 6 ）： 82 - 86 ．

Zhou WT ， Yang TT ， Xu WQ ， et al . The polysaccharides from the fruits of Lycium barbarum L. confer anti-diabetic effect by regulating gut microbiota and intestinal barrier [J ] . Carbohydr Polym ， 2022 ， 291 ： 119626 ．

Ma X ， Pan Y ， Zhao W ， et al . Bifidobacterium infantis strain YLGB-1496 possesses excellent antioxidant and skin barrier-enhancing efficacy in vitro [J ] . Exp Dermatol ， 2022 ， 31 （ 7 ）： 1089 - 1094 ．

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

To explore the mechanism of Xiaoyao Yiji decoction in the treatment of IBS-D by the 16s rRNA sequencing combined with metabolomics

Clinical study on the correlation between hepatitis C and thyroid dysfunction

Features of intestinal flora and their association with traditional Chinese medicine syndrome types in elderly eczema patients with different severities

Correlation between coronary heart disease and intestinal flora

Related Author

Wang Yangyang

Ma Fang

Chen Chu

Wang Mengfei

Su Heng

Niu Ben

Zhang Yating

Liao Qian

Related Institution

The First Clinical Medical College of Shaanxi University of Chinese Medicine

Department of Clinical Laboratory，Shaanxi Hospital of Traditional Chinese Medicine

Department of Clinical Laboratory，Honghui Hospital，Xi 'an Jiaotong University

Department of Endocrinology and Metabolism，The Affiliated Hospital of Kunming University of Science and Technology/The First People’s Hospital of Yunnan Province

Department of Dermatology，Chengdu University of Traditional Chinese Medicine Affiliated Hospital

⁰