仙方活命饮加减方减轻脓毒症致大鼠肝损伤的机制研究  

Study on the mechanism of modified Xianfang huoming decoction relieving sepsis-induced liver injury in rats

作　　者：李自辉 刘静姝 李东霞[2] 董毅[3] 张宝文[2] 高明[2] LI Zihui;LIU Jingshu;LI Dongxia;DONG Yi;ZHANG Baowen;GAO Ming(College of Life and Health,Dalian University,Liaoning Dalian 116622,China;Medical College,Dalian University,Liaoning Dalian 116622,China;Dept.of Traditional Chinese Medicine,Xinhua Hospital Affiliated to Dalian University,Liaoning Dalian 116000,China)

机构地区：[1]大连大学生命健康学院,辽宁大连116622 [2]大连大学医学院,辽宁大连116622 [3]大连大学附属新华医院中医科,辽宁大连116000

出　　处：《中国药房》2023年第11期1343-1348,共6页China Pharmacy

基　　金：国家中医药管理局全国名老中医药专家传承工作室建设项目(No.国中医药人教函〔2022〕75号)。

摘　　要：目的从肠道菌群与代谢组学的角度探究仙方活命饮加减方防治脓毒症致肝损伤的作用机制。方法采用体质量均衡分配法将60只SD大鼠分为空白组(生理盐水)、模型组(生理盐水)、阳性对照药组(地塞米松片,5.0 mg/kg)和仙方活命饮加减方高、中、低剂量组(以生药计分别为6.0、3.0、1.5 g/kg),每组10只。灌胃相应药物/生理盐水,灌胃体积均为10 mL/kg;每天给药1次,连续14 d。末次给药后,除空白组外,其余各组大鼠均腹腔注射脂多糖10 mg/kg建立脓毒症模型。造模12 h后,检测大鼠血清中炎症指标[白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)]和肝功能指标[总胆固醇(TC)、甘油三酯(TG)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)]水平;采用16S rRNA技术联合肝脏代谢组学分析大鼠肠道菌群及肝脏代谢产物的变化。结果仙方活命饮加减方可显著改善脓毒症致肝损伤大鼠血清中炎症指标与肝功能指标(P<0.05或P<0.01),对5种优势菌门中11种菌属(如阿克曼氏菌属、乳杆菌属、沃氏嗜胆菌属等)的相对丰度有显著回调作用(P<0.05或P<0.01)。共鉴定出甘氨胆酸、磷脂酰胆碱、牛磺酸等12个与该方改善脓毒症致肝损伤相关的潜在生物标志物(P<0.05或P<0.01),主要涉及甘油磷脂代谢、嘌呤代谢和初级胆汁酸代谢等代谢通路。结论仙方活命饮加减方可通过调节肠道菌群和肝脏代谢,改善脓毒症致肝损伤。OBJECTIVE To explore the mechanism of modified Xianfang huoming decoction in the treatment of sepsisinduced liver injury from the perspective of gut microbiota and metabolites.METHODS Sixty SD rats were divided into blank group(normal saline),model group(normal saline),positive control drug group(Dexamethasone tablet,5.0 mg/kg),modified Xianfang huoming decoction high-dose,middle-dose and low-dose groups(6.0,3.0,1.5 g/kg,calculated by crude drug)according to equilibrium-partitioning approach of body mass,with 10 rats in each group.They were given relevant drug/normal saline 10 mL/kg,once a day,for consecutive 14 days.After the last medication,except for blank group,other groups were given intraperitoneal injection of lipopolysaccharide 10 mg/kg to induce sepsis model.Twelve hours after modeling,serum levels of inflammatory indexes in rats[interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)]and liver function indicators[total cholesterol(TC),triglyceride(TG),aspartate transaminase(AST),alanine transaminase(ALT)]were detected.The changes of gut microbiota and liver metabolites in rats were analyzed by 16S rRNA technology and liver metabolomics.RESULTS Modified Xianfang huoming decoction could significantly improve the indexes of serum inflammatory indexes and liver function in rats with sepsis-induced liver injury(P<0.05 or P<0.01);there was a significant callback effect on the relative abundance of 11 genera of bacteria(such as Akkermansia,Lactobacillus and Bilophila)among the 5 dominant phyla(P<0.05 or P<0.01).Twelve metabolites related to liver injury caused by sepsis were identified,such as glycine cholic acid,phosphatidylcholine,taurine(P<0.05 or P<0.01),mainly involving glycerol phospholipid metabolism,purine metabolism and primary bile acid metabolism.CONCLUSIONS Modified Xianfang huoming decoction can improve liver injury induced by sepsis by regulating gut microbiota and liver metabolites.

关 键 词：仙方活命饮加减方 脓毒症 肠道菌群 代谢组学 16S rRNA技术 肝损伤 

分 类 号：R285.5[医药卫生—中药学]