芍药苷调控色氨酸代谢对CKD小鼠便秘的改善作用  

Paeoniflorin alleviates constipation in CKD mice by regulating tryptophan metabolism

作　　者：邱军 聂蕙斌 姚凤华 韩博 占煜 QIU Jun;NIE Huibin;YAO Fenghua;HAN Bo;ZHAN Yu(Department of Nephrology,Southern District of the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100071,China;Department of Nephrology,Integrated TCM and Western Medicine Hospital Affiliated to Chengdu University of Traditional Chinese Medicine,Chengdu 610095,China;Department of Proctology,Integrated TCM and Western Medicine Hospital Affiliated to Chengdu University of Traditional Chinese Medicine,Chengdu 610095,China)

机构地区：[1]解放军总医院第五医学中心南院肾病科,北京100071 [2]成都中医药大学附属中西医结合医院肾病科,四川成都610095 [3]成都中医药大学附属中西医结合医院肛肠科,四川成都610095

出　　处：《药学研究》2025年第4期328-333,共6页Journal of Pharmaceutical Research

基　　金：国家自然科学基金青年科学基金项目(No.82004173);四川省中医药管理局中医药科研专项课题面上项目(No.2024MS183、2024MS610)。

摘　　要：目的探讨芍药苷(PF)对腺嘌呤诱导的慢性肾脏病(CKD)小鼠便秘症状的改善效果。方法将30只C57BL/6小鼠随机分为对照组、模型组、利那洛肽组和芍药苷低、高剂量组,每组6只。除对照组外,其余小鼠以0.2%腺嘌呤饲料喂养6周,建立CKD伴便秘模型。芍药苷低、高剂量组分别以100和200 mg·(kg·d)^(-1)芍药苷灌胃,利那洛肽组给予100μg·(kg·d)-1利那洛肽混悬液灌胃。对照组和模型组给予等量蒸馏水,持续14 d。检测小鼠的粪便含水量、肠道转运时间、肠道推进率,采用蛋白免疫印迹法(WB)检测TPH1、AHR、IDO1蛋白表达。收集小鼠肠内容物进行肠道菌群测序,探索芍药苷对肠道菌群的影响。结果与对照组相比,模型组小鼠血肌酐和尿素氮升高,粪便含水量减少,肠道转运时间延长,推进率降低,结肠TPH1、AHR蛋白表达下调(P<0.05)。与模型组相比,芍药苷组小鼠的血肌酐和尿素氮水平下降,粪便含水量和肠道推进率增加,肠道转运时间缩短,结肠TPH1、AHR蛋白表达上调(P<0.05)。此外,肠道菌群测序结果提示芍药苷具有改变CKD小鼠粪便菌群结构的作用。结论芍药苷能改善腺嘌呤诱导的CKD小鼠便秘症状,其机制可能与调控肠道色氨酸代谢有关。Objective To investigate the effect of paeoniflorin(PF)on improving constipation symptoms in adenine-induced chronic kidney disease(CKD)mice.Methods Thirty C57BL/6 mice were randomly assigned to five groups:control,model,linaclotide,and low-and high-dose paeoniflorin groups,with six mice in each group.To induce the CKD model,mice in all groups except the control were fed a 0.2%adenine diet for six weeks.The low-and high-dose paeoniflorin groups were administered 100 and 200 mg·(kg·d)^(-1)of paeoniflorin via gavage,respectively,while the linaclotide group received 100μg·(kg·d)^(-1)of linaclotide suspension via gavage,serving as a positive control for constipation treatment.The control and model groups were given an equivalent volume of distilled water for 14 days.Fecal water content,intestinal transit time,and intestinal motility were measured to assess the severity of constipation.The expression of key proteins involved in tryptophan metabolism(TPH1,AHR,and IDO1)were quantified by Western blotting.Intestinal contents of mice were collected for intestinal flora sequencing to explore the effect of paeoniflorin on intestinal flora.Results Compared to the control group,the model group showed significantly elevated serum creatinine and blood urea nitrogen levels,decreased fecal water content,prolonged intestinal transit time,reduced motility,and downregulated colonic TPH1,and AHR protein expression(P<0.05).Compared with the model group,the paeoniflorin-treated mice exhibited decreased serum creatinine and blood urea nitrogen levels,increased fecal water content and intestinal motility,shortened transit time,and upregulated colonic TPH1,and AHR protein expression(P<0.05).Furthermore,gut microbiome sequencing data indicated that paeoniflorin significantly modulated the composition of fecal microbiota in adenine-induced CKD mice.Conclusion Paeoniflorin significantly alleviates constipation symptoms in adenine-induced CKD mice,possibly through the regulation of intestinal tryptophan metabolism.

关 键 词：慢性肾脏病 便秘 芍药苷 色氨酸代谢 

分 类 号：R285.5[医药卫生—中药学]