文献类型：期刊文献

中文题名：N-乙酰半胱氨酸缓解顺铂肝损伤的作用机制研究

英文题名：Study on the mechanism of N-acetylcysteine in alleviating cisplatin-induced liver injury

作者：杨必乾[1];何慧明[1];殷亭湄[2];付晓艳[2];高广淼[2];杨玲玲[2];李洁[2];连小龙[3];邓毅[2]

第一作者：杨必乾

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

第一机构：广元市中医医院药剂科,广元628000

年份：2025

卷号：50

期号：6

起止页码：815

中文期刊名：重庆医科大学学报

外文期刊名：Journal of Chongqing Medical University

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(编号:81960723);甘肃省科技计划资助项目(编号:21JR11RA145)。

语种：中文

中文关键词：药源性肝损伤;N-乙酰半胱氨酸;肝指数;肝功能;肠道菌群

外文关键词：drug-induced liver injury;N-acetylcysteine;liver index;liver function;intestinal flora

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(P=0.000),而NAC组大鼠肝指数相较于CP组明显下降(P=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(P=0.006,P=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。
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 factorkappa 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-αin 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(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=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(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in theα-diversity index of intestinal flora,while compared with the CP group,the NAC group tended to have a reduction in theα-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.