痛风宁对高尿酸血症脾虚湿盛证模型小鼠肠道菌群及肠道尿酸代谢的影响  

Effects of Tongfengning(痛风宁) on Intestinal Flora and Intestinal Uric Acid Metabolism in Model Mice of Hyperuricemia of Spleen Deficiency with Exuberance of Dampness Syndrome

作　　者：张英杰 毛骁 肖艳 蔡唐彦 郭洁梅 陈鹏 张鹏 刘俊 陈雨 邱梦婷 苏友新 ZHANG Yingjie;MAO Xiao;XIAO Yan;CAI Tangyan;GUO Jiemei;CHEN Peng;ZHANG Peng;LIU Jun;CHEN Yu;QIU Mengting;SU Youxin(School of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122;Zhoupu Community Health Service Center of Xihu District;School of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine;Fujian Health College)

机构地区：[1]福建中医药大学中医学院,福建福州350122 [2]浙江省杭州市西湖区周浦社区卫生服务中心 [3]福建中医药大学康复医学院 [4]福建卫生职业技术学院

出　　处：《中医杂志》2023年第21期2232-2240,共9页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81973891);国家中医药管理局2021年岐黄学者支持项目(国中医药人教函[2022]6号);福建省卫生健康委员会医学创新课题(2019-CX-40)。

摘　　要：目的 探讨痛风宁治疗高尿酸血症(HUA)脾虚湿盛证的可能作用机制。方法 60只小鼠中随机选取10只作为正常组常规饲喂,其余50只予高脂高糖饲料联合劳倦过度+次黄嘌呤联合氧嗪酸钾混悬液构建HUA脾虚湿盛证病证结合动物模型。造模成功后为更好地观察痛风宁对模型小鼠肠道菌群的影响,在维持病证结合造模的基础上,采用混合抗生素混悬液灌胃,诱导加重模型小鼠肠道菌群紊乱。造模成功的50只小鼠随机分为模型组、痛风宁组、别嘌醇组、益生菌组、别嘌醇+益生菌组,每组10只。痛风宁组以19.11 g/(kg·d)痛风宁药液灌胃,别嘌醇组以78 mg/(kg·d)别嘌醇混悬液灌胃,益生菌组以3 g/(kg·d)双歧杆菌乳杆菌三联活菌片混悬液灌胃,别嘌醇+益生菌组以78 mg/(kg·d)别嘌醇及3 g/(kg·d)双歧杆菌乳杆菌三联活菌片混悬液灌胃,正常组、模型组以19.11 ml/(kg·d)生理盐水灌胃;均连续干预21天。为了维持稳定的高血尿酸状态,除正常组外,其余各组小鼠在给药干预的同时均继续进行造模。比较各组小鼠脾虚证候积分,血尿酸水平,菌群结构的变化,肠道灌洗液中乙酸、丁酸含量,小肠组织中腺苷脱氨酶(ADA)、黄嘌呤氧化酶(XOD)含量,三磷酸腺苷结合盒转运蛋白G2 (ABCG2)、葡萄糖转运体9 (GLUT9)蛋白及mRNA表达。结果 与正常组比较,模型组脾虚证候积分、血尿酸水平、厚壁菌门相对丰度、厚壁菌门/拟杆菌门值,副拟杆菌属、克雷伯菌属、肠球菌属丰度,肠道灌洗液乙酸含量,小肠组织中ADA及XOD含量、GLUT9蛋白及mRNA表达升高(P<0.05);肠道菌群操作分类单元(OTU)数目、拟杆菌门相对丰度,乳杆菌属、未培养拟杆菌属丰度,肠道灌洗液丁酸含量,小肠组织中ABCG2蛋白及mRNA表达显著降低(P<0.05)。与模型组比较,痛风宁组、益生菌组、别嘌醇+益生菌组小鼠脾虚证候积分、血尿酸水平、厚壁菌门相对丰度、肠道灌�Objective To explore the possible mechanisms of Tongfengning (痛风宁,TFN) in treating hyperuricemia(HUA) of spleen deficiency with exuberance of dampness syndrome.Methods Ten of 60 mice were randomly selected,and were fed with regular diet as the control group,while the remaining 50 mice were fed with high-fat and high-sugar diet combined with excessive exercise and potassium oxonate-allopurinol suspension to establish an HUA animal model of syndrome of spleen deficiency with exuberance of dampness.After the successful modeling,in order to better observe the effects of TFN on the intestinal microbiota of the model mice,a mixed antibiotic suspension was administered by gavage to induce further dysbiosis of the intestinal microbiota in the model mice.Fifty sucessfully modeled mice were randomly divided into model group,TFN group,allopurinol group,probiotics group,and an allopurinol + probiotics group,10 in each group.The TFN group was administered TFN liquid at a dosage of 19.11 g/(kg·d) by gavage.The allopurinol group was administered allopurinol suspension at a dosage of 78 mg/(kg·d) by gavage.The probiotics group was administered live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/(kg·d) by gavage.The allopurinol + probiotics group was administered allopurinol at a dosage of 78 mg/(kg·d) and live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/(kg·d) by gavage.The control group and model group were administered normal saline at a dosage of 19.11 ml/(kg·d) by gavage.The interventions were continued for 21 days.In order to maintain a stable high blood uric acid state,all groups but the control group continued modeling while receiving drug intervention.The changes in spleen deficiency syndrome scores,blood uric acid levels,microbial community structure,acetic acid and butyric acid content in intestinal lavage fluid,adenosine deaminase(ADA) and xanthine oxidase(XOD) content in small intestine tissue,as well as ATP-binding cassette transporte

关 键 词：高尿酸血症 肠道菌群 尿酸代谢 脾虚湿盛证 痛风宁 

分 类 号：R285.5[医药卫生—中药学]