毛菊苣正丁醇部位调节肠道菌群-肠-肝轴防治大鼠慢性肝病的研究  

Ameliorates Study of N-butanol Extract of Cichorium Pumilum Jacq on Chronic Liver Diseases of Rats by Regulating Intestinal Flora-Intestine-Hepatic Axis

作　　者：李聪 邹楠[2] 袁今奇[2] 姚佳 苏林洁 韩畅 秦冬梅 LI Cong;ZOU Nan;YUAN Jinqi;YAO Jia;SU Linjie;HAN Chang;QIN Dongmei(Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education,School of Pharmacy,Shihezi University,Shihezi 832002,China;Department of Traditional Chinese Medicine, the First Affiliated Hospital,School of Medicine,Shihezi University,Shihezi 832002,China)

机构地区：[1]石河子大学药学院/新疆植物药资源利用教育部重点实验室,石河子832002 [2]石河子大学医学院第一附属医院中医科,石河子832002

出　　处：《医药导报》2022年第8期1108-1115,共8页Herald of Medicine

基　　金：国家自然科学基金资助项目(82160742);新疆生产建设兵团重大科技项目(2020AA005)。

摘　　要：目的探讨毛菊苣正丁醇部位是否能通过调节肠道菌群-肠-肝轴防治慢性肝病。方法采用5%三硝基苯磺酸(TNBS)-80%乙醇(EtOH)以60 mg·kg^(-1)的剂量对大鼠进行长期灌肠,构建由肠道损伤导致的肝损伤模型,每周灌肠2次,连续12周,第13周时,分组给药:毛菊苣正丁醇部位小剂量组(100 mg·kg^(-1))、毛菊苣正丁醇部位大剂量组(150 mg·kg^(-1))、柳氮磺吡啶肠溶片组(100 mg·kg^(-1))灌胃给予相应剂量的治疗药物,正常对照组和模型对照组灌胃等量0.9%氯化钠溶液,每天给药1次。2周后,将大鼠安乐死,试剂盒检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、γ-谷氨酰转肽酶(γ-GT)和白蛋白(ALB)水平,苏木精-伊红(HE)染色和Masson染色观察肠道和肝脏的组织病理学变化,酶联免疫吸附测定(ELISA)检测肝组织中白细胞介素(IL)-4、IL-6和肿瘤坏死因子(TNF)-α的含量,采用16SrDNA对粪便进行测序,分析微生物种类。体外实验分析毛菊苣正丁醇部位对青春双歧杆菌和嗜酸乳杆菌生长的影响。结果与模型对照组相比,毛菊苣正丁醇部位干预后:①毛菊苣正丁醇部位小剂量组血清ALT和γ-GT水平显著降低(P<0.05),LDH水平降低,差异无统计学意义(P>0.05),大剂量组血清ALT、γ-GT、LDH水平降低差异无统计学意义(P>0.05),大、小剂量组AST和ALB水平均没有得到改善;②大、小剂量组肝肠组织的炎性细胞浸润均减轻、病理状态得到改善;③大剂量组肝组织匀浆IL-6和TNF-α水平显著降低(P<0.01);④大剂量组厚壁菌门、颤螺菌属和瘤胃球菌属的丰度升高,变形菌门和拟杆菌门的丰度降低,肠道菌群接近正常水平;⑤体外实验毛菊苣正丁醇部位浓度在0~0.0975 mg·mL^(-1)时,可促进青春双歧杆菌生长,基本不影响嗜酸乳杆菌生长。结论毛菊苣正丁醇部位防治由肠道炎症诱导的肝损伤可能是通过调节肠道菌群紊乱,恢�Objective The aim of this study was to explore whether the n-butanol part extract of Cichorium pumilum Jacq could prevent and treat chronic liver diseases by regulating the intestinal flora-intestinal-hepatic axis.Methods A liver-injury model induced by intestinal injury was constructed by a long-term enucleation of rats with 5%trinitrobenzene sulfonic acid(TNBS)-80%ethanol(EtOH)solution at a dose of 60 mg·kg^(-1),twice a week for 12 weeks.And at the 13th week,the drug was administered to groups:The rats in the small dose group(100 mg·kg^(-1)),the large dose group(150 mg·kg^(-1)),and the enteric soluble tablet group(100 mg·kg^(-1))were given the corresponding doses of the extract by gavage,and the rats in the normal control group and the model control group were given equal amounts of 0.9%sodium chloride solution by gavage once daily.After two weeks,rats were euthanized,and serum ALT,AST,LDH,γ-GT,and ALB levels were detected by test kits.The histopathological changes in the intestine and liver were observed by HE staining and Masson staining.The levels of IL-4,IL-6,and TNF-αin liver tissues were measured by an enzyme-linked immunosorbent assay(ELISA),and feces were sequenced using 16SrDNA to analyze microbial species.In vitro experiments were performed to analyze the effect of n-butanol part extract of Cichorium pumilum Jacq on Bifidobacterium adolescentis and Lactobacillus acidophilus growth.Results Compared with the model control group,after the intervention of n-butanol part extract of Cichorium pumilum Jacq,the serum ALT andγ-GT levels in the low-dose group was significantly reduced(P<0.05).LDH levels were reduced,and the difference was not statistically significant(P>0.05).Serum ALT,γ-GT,and LDH levels in the large dose group were reduced,and the difference was not statistically significant(P>0.05).AST and ALB levels in the large and small dose groups levels in both high and low dose groups did not improve.The inflammatory cell infiltration in liver and intestinal tissues was reduced,and the patholog

关 键 词：毛菊苣 慢性肝病 肠道菌群-肠-肝轴 炎症 

分 类 号：R921[医药卫生—药学] R657.3