肠道微生物网络在高草酸诱导大鼠肾损伤中的保护作用  

Protective role of intestinal microbial network in hyperoxaluria⁃induced kidney impairment in rats

作　　者：王演 潘铁军 刘振宇 孙进波 周宇 李超圣 高磊 WANG Yan;PAN Tiejun;LIU Zhenyu;SUN Jinbo;ZHOU Yu;LI Chaosheng;GAO Lei(Department of Urology,the Gen-eral Hospital of Central Theater Command of Chinese People′s Liberation Army,Wuhan 430000,China)

机构地区：[1]中国人民解放军中部战区总医院泌尿外科,武汉430000

出　　处：《实用医学杂志》2024年第13期1771-1777,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81502210);中部战区总医院育英计划面上项目(编号:ZZY202211,ZZYCZ202101)。

摘　　要：目的探讨肠道菌群移植(FMT)对高草酸饮食大鼠草酸代谢的影响及肾脏保护作用。方法将24只雄性SD大鼠随机分为SC组、SC+FMT组、OD+PBS组及OD+FMT组。其中,SC组为对照组,正常大鼠饲料喂养;OD+PBS组及OD+FMT组采用5%草酸含量的饲料喂养。第14天起,OD+PBS组、OD+FMT组及SC+FMT组分别给予PBS溶液及豚鼠粪便滤液灌胃,连续7 d。收集各组大鼠的24 h尿液、粪便及静脉血清,测定肠道菌群及血清尿液生化指标;取大鼠肾脏进行实时定量PCR及免疫组化检测肾素、ACE及OPN的表达情况。结果肠道菌群移植影响了大鼠的肠道菌群,SC+FMT组大鼠的肠道菌群偏离了SC组大鼠的肠道菌群并与豚鼠肠道菌群的相似度提高;与OD+PBS组比较,OD+FMT组的尿草酸、尿素、尿酸、肌酐、血尿素氮/肌酐以及血尿酸明显降低。此外,经FMT治疗后,与OD+PBS组相比,OD+FMT组上调的肾素mRNA表达的被降低,下调的OPN mRNA表达得到了恢复;免疫组化得到了类似的结果。结论肠道菌群移植激活了大鼠肠道中以Muribaculaceae等草酸降解菌为代表的微生物网络。高草酸诱导的肾脏损伤因微生物网络对草酸的降解而恢复,肠道菌群移植对大鼠肾脏具有保护作用。Objective To explore the effects of fecal microbiota transplantation(FMT)on oxalate metabolism and renal protection in rats fed a high oxalate diet.Methods Twenty-four male SD rats were randomly divided into four groups:SC,SC+FMT,OD+PBS and OD+FMT.The SC group was set as the control group and was fed standard rat chow.The OD+PBS group and OD+FMT group were fed a diet containing 5%oxalate.Starting from day 14,the OD+PBS group,OD+FMT group and SC+FMT group received intragastric administration of PBS solution or filtered faecal microbiota solution from guinea pigs for 7 consecutive days.The 24-hour urine,feces,and venous serum of the rats were collected from the rats of all groups to determine the gut microbiota and biochemical markers.Real-time quantitative PCR and immunohistochemistry were conducted on the rat kidneys to detect the expression of renin,ACE,and OPN.Results The fecal microbiota transplantation altered the gut microbiota of rats.The gut microbiota of the SC+FMT group deviated from that of the SC group and showed increased similarity to that of the guinea pigs.Compared to the OD+PBS group,the OD+FMT group exhibited significant reductions in the urinary oxalate,urinary urea,uric acid,urinary creatinine,serum urea nitrogen/creati-nine,and serum uric acid.Furthermore,after FMT treatment,the OD+FMT group exhibited reduced upregulation of renin mRNA expression and restored downregulation of OPN mRNA expression compared to the OD+PBS group;similar results were obtained from immunohistochemistry.Conclusion Fecal microbiome trans-plantation activated the microbial network in the rat gut,particularly the oxalate-degrading bacteria represented by Muribaculaceae.The kidney injury induced by high oxalate was partially restored by the microbiota network's degradation of oxalate,indicating the protective effect of fecal microbiota transplantation on the rat kidneys.

关 键 词：肠道菌群移植 微生物网络 草酸钙结石 肾脏保护 

分 类 号：R446.139[医药卫生—诊断学]