解毒护肝通络方对药物性肝损伤小鼠的保护作用及其对肠道菌群和肠黏膜屏障的影响  

Protective Effect of Jiedu Hugan Tongluo Recipe on Drug-Induced Liver Injury Mice and its Effects on Intestinal Flora and Intestinal Mucosal Barrier

作　　者：李思潼 彪雅宁 刘晨旭 顾亚茹 胡巍巍[2] 路帅[2] 张一昕 LI Sitong;BIAO Yaning;LIU Chenxu;GU Yaru;HU Weiwei;LU Shuai;ZHANG Yixin(Hebei University of Chinese Medicine,International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province,Shijiazhuang 050200,China;Shijiazhuang Medical College,Shijiazhuang 050599,China)

机构地区：[1]河北中医药大学河北省中药资源利用与质量评价国际联合研究中心,石家庄050200 [2]石家庄医学高等专科学校,石家庄050599

出　　处：《世界科学技术-中医药现代化》2024年第2期351-359,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：河北省中医药管理局科研计划项目(2020308):解毒护肝方防治药物性肝损伤的作用及氧化应激机制,负责人:胡巍巍;河北省高等学校科学技术研究项目(BJ2016038):解毒护肝方防治药物性肝损伤的防治作用及机制研究,负责人:王茜。

摘　　要：目的探讨解毒护肝通络方对药物性肝损伤(DILI)小鼠的保肝作用及其机制。方法将C57BL/6N小鼠60只,随机分为正常组、对乙酰氨基酚(APAP)组、阳性药(水飞蓟宾)组及解毒护肝通络方高、中、低剂量组。上午采用APAP药液灌胃复制DILI小鼠模型,下午灌胃相应药物治疗,持续14天。小鼠处死后,收集血清、肝脏、回肠、结肠组织以及粪便用于后续指标检测。结果与正常组比,APAP组小鼠血清中谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、直接胆红素(direct bilirubin,DBIL)、总胆红素(total bilirubin,TBIL)和脂多糖(lipopolysaccharide,LPS)的含量或活性均显著升高(P<0.01),肝脏、回肠和结肠组织均出现病理损伤,小肠绒毛高度、隐窝深度、菌群丰富度和多样性、肠道组织闭合蛋白(Occludin)和闭锁小带蛋白-1(ZO-1)表达水平以及拟杆菌门和S24-7相对丰度均显著降低(P<0.01,P<0.05),厚壁菌门、厚壁菌门与拟杆菌门比值(F/B)和毛螺菌科相对丰度升高(P<0.01,P<0.05)。与APAP组比,解毒护肝通络方能显著改善小鼠肝功能以及肝脏、回肠和结肠组织病理损伤,降低血清LPS含量(P<0.01),升高小肠绒毛高度、隐窝深度、菌群丰富度和多样性、肠道组织中occludin和ZO-1蛋白表达水平以及拟杆菌门、S24-7的相对丰度(P<0.01,P<0.05),降低F/B、厚壁菌门和毛螺菌科相对丰度(P<0.01)。结论解毒护肝通络方可能通过恢复肠道菌群失调,保护肠黏膜屏障,降低肠道通透性,进而达到保肝的目的。Objective To explore the hepatoprotective effect and mechanism of Jiedu Hugan Tongluo Recipe on druginduced liver injury(DILI)mice.Methods 60 C57BL/6N mice were randomly divided into control group,acetaminophen(APAP)group,silybin group and high-,medium-,and low-dose Jiedu Hugan Tongluo Recipe groups.Mice model of DILI were gavage by APAP in the morning,and corresponding drugs were given intragastric administration in the afternoon for 2 weeks.After the rats were sacrificed,serum,liver,ileum,colon tissues and feces were collected to be used in subsequent experiments.Results Compared with the normal group,mice in the APAP group showed the significant increase in the contents or activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST),indirect bilirubin(DBIL),total bilirubin(TBIL)and lipopolysaccharide(LPS)in serum(P<0.01),the notably decrease in small intestinal villus height and crypt depth,the diversity and abundance of intestinal flora,Occludin and ZO-1 protein expression in intestine as well as the relative abundance of Bacteroidetes and S24-7(P<0.01,P<0.05).Moreover,pathological injury were observed in liver,ileum and colon tissues.The relative abundance of Firmicutes and Lachnospiraceae,the value of Firmicutes and Bacteroidetes(F/B)were increased(P<0.01,P<0.05).Jiedu Hugan Tongluo Recipe notably alleviated liver function and the pathological injury in liver,ileum and colon tissues,decreased the LPS content in serum(P<0.01),increased the small intestinal villus height and crypt depth,the diversity and abundance of intestinal flora,the expression of occludin and ZO-1 protrin in intestine as well as the relative abundance of Bacteroidetes and S24-7(P<0.01,P<0.05),decreased the relative abundance of Firmicutes and Lachnospiraceae,as well as the value of F/B(P<0.01).Conclusion Jiedu Hugan Tongluo Recipe may treat DILI by regulating the intestinal flora,protecting the intestinal mucosal barrier and lowing the intestinal permeability.

关 键 词：解毒护肝通络方 药物性肝损伤 对乙酰氨基酚 肠道菌群 肠黏膜屏障 

分 类 号：R285.5[医药卫生—中药学]