摘要
目的:探讨解毒护肝方防治药物性肝损伤(DILI)的作用与肠道微生态的相关性。方法:60只C57BL/6N小鼠随机分为正常组、模型组、水飞蓟宾组及解毒护肝方低、中、高剂量组。采用对乙酰氨基酚(APAP)药液灌胃复制DILI模型,造模同时给予相应药物治疗,连续14 d。半自动生化仪检测血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)和直接胆红素(DBIL)的含量或活性,苏木素-伊红(HE)染色法观察肝脏病理形态,16SrRNA测序法分析粪便中肠道菌群组成结构。结果:与正常组比,模型组小鼠血清中ALT、AST、DBIL、TBIL的含量或活性均显著升高(P<0.01),肝细胞内可见大量的嗜酸性变和炎性细胞浸润,Chao1、Observed species、Simpson和Shannon指数均显著降低(P<0.01或P<0.05),厚壁菌门、变形菌门相对丰度以及厚壁菌门/拟杆菌门(F/B)值均明显升高(P<0.01或P<0.05),拟杆菌门相对丰度明显降低(P<0.05)。与模型组比,解毒护肝方能显著改善肝组织病理损伤,显著降低血清中ALT、AST、DBIL、TBIL的含量或活性(P<0.01或P<0.05),显著升高Chao1、Observed species、Simpson、Shannon指数以及拟杆菌门相对丰度(P<0.01或P<0.05),显著降低厚壁菌门、变形菌门相对丰度以及F/B值(P<0.01)。相关性分析结果表明,厚壁菌门、变形菌门相对丰度与肝损伤标志物成正相关,而拟杆菌门相对丰度与肝损伤标志物成负相关。结论:解毒护肝方防治DILI的机制可能与改善肠道菌群失衡有关。
Objective:to explore the correlation between the effect of Jiedu Hugan Formula on preventing and treating drug-induced liver injury(DILI) and intestinal microecology.Methods:Sixty C57BL/6N mice were randomly divided into normal group,model group,Silybum marianum group and low,middle and high dose groups of Jiedu Hugan Formula.The DILI model was established by intragastric administration of Acetaminophen(APAP) solution,with corresponding drug treatment at the same time for 14 consecutive days.The content or activity of alanine aminotransferase(ALT),aspartate transaminase(AST),total bilirubin(TBIL) and direct bilirubin(DBIL) in serum were detected by semi-automatic biochemical analyzer.The pathological morphology of liver was observed by hematoxylin eosin(HE) staining,and the composition and structure of intestinal flora in feces were analyzed by 16SrRNA sequencing.Results:Compared with the normal group,the content or activity of ALT,AST,DBIL,TBIL in the serum of the model group significantly increased(P<0.01),a large number of eosinophilic and inflammatory cell infiltration seen in liver cells,Chao1,Observed specifications,Simpson,and Shannon indices all significantly decreased(P<0.01 or P<0.05),the relative abundance and F/B value of Bacillota and Pseudomonadota increased significantly(P<0.01 or P<0.05),while the relative abundance of Bacteroidota decreased significantly(P<0.05).Compared with the model group,Jiedu Hugan Formula could significantly improve the pathological damage of liver tissue,significantly reduce the content or activity of ALT,AST,DBIL,TBIL in serum(P<0.01 or P<0.05),significantly increased Chao1,Observed specifications,Simpson,Shannon indices and the relative abundance of Bacteroidota(P<0.01 or P<0.05),significantly reduced the relative abundance and F/B value of Bacillota and Pseudomonadota(P<0.01).The correlation analysis showed that the relative abundance of Bacillota and Pseudomonadota was positively correlated with liver injury markers,while the relative abundance of Bacteroidota was nega
作者
胡巍巍
彪雅宁
彭小园
巨晓
刘晨旭
路帅
张一昕
HU Wei-wei;BIAO Ya-ning;PENG Xiao-yuan;JU Xiao;LIU Chen-xu;LU Shuai;ZHANG Yi-xin(Shijiazhuang Medical College,Shijiazhuang 050599)
出处
《河北中医药学报》
2023年第4期5-10,共6页
Journal of Hebei Traditional Chinese Medicine and Pharmacology
基金
国家自然科学基金资助项目:No.81503268
河北省中医药管理局科研计划项目:No.2020308。
关键词
解毒护肝方
药物性肝损伤
胁痛
黄疸
药毒
对乙酰氨基酚
肠道菌群
Jiedu Hugan Formula
drug-induced liver injury
hypochondriac pain
jaundice
drug toxicity
APAP
intestinal flora
