醋酸泼尼松长期治疗对阿霉素肾病大鼠肠道菌群的影响

The compositional alteration of gut microbiota in rats with adriamycin-induced nephrotic syndrome after long-term prednisone treatment

目的观察醋酸泼尼松长期治疗对阿霉素肾病大鼠肠道菌群结构的影响。方法取SD大鼠16只,通过尾静脉注射阿霉素(7.5mg/kg体重)构建阿霉素肾病大鼠模型。随机将阿霉素肾病大鼠分为对照组和醋酸泼尼松治疗组,醋酸泼尼松治疗组采用10mg/kg体重的醋酸泼尼松连续6周灌胃治疗,收集大鼠粪便进行16SrRNA基因测序及生物信息学分析,比较两组大鼠肠道微生物丰度及多样性变化,并进行差异菌属的鉴定。结果16SrRNA基因测序显示,醋酸泼尼松治疗后,阿霉素肾病大鼠肠道微生物群的丰度和多样性与对照组比较,差异均无统计学意义(均P>0.05)。在肠道微生物群门水平,醋酸泼尼松治疗组软壁菌门相对丰度增加(P<0.05);在属水平,治疗组异芽孢杆菌属相对丰度升高(P<0.05),双歧杆菌属、拟普雷沃菌属和施氏菌属相对丰度下降(均P<0.05)。对肠道微生物群的功能进行预测分析,醋酸泼尼松长期治疗后阿霉素肾病大鼠肠道菌群与内分泌代谢、癌症通路、萜类和聚酮化合物的代谢、细菌侵袭上皮细胞、限制性内切酶等相关的代谢通路均显著增强(均P<0.05);寄生虫、脂质代谢、免疫疾病、异生物素的生物降解和代谢、环境适应、其他次生代谢产物的生物合成等代谢通路均显示减弱(均P<0.05)。结论醋酸泼尼松长期治疗对阿霉素肾病大鼠肠道菌群的丰度和多样性无显著影响,但部分肠道有益菌减少,异杆菌属丰度增加,这提示肠道菌群结构的改变可能与醋酸泼尼松的疗效及毒副作用相关。

Objective To investigate the compositional changesof gut microbiota in rats with adriamycin-induced nephrotic syndrome after long-term prednisone treatment.Methods Sixteen SD rats with adriamycin-induced nephrotic syndrome established by single injection of adriamycin(7.5 mg/kg)in tail vein were randomly divided into Control and Prednisone groups.Rats in Prednisone group was treated with prednisone(10 mg/kg)by gavage for 6 consecutive weeks.Thereafter,the stool samples were collected for gut microbiota analysis by using 16S rRNA sequencing assay and bioinformatics analysis.The intestinal microbial abundance and diversity were compared between the two groups.The differential abundant bacteria were identified by performing metastats analysis Results The 16S rRNA sequencing results showed that there were no significant differences in the abundance and diversity of the gut microbiota between Control and Prednisone group(P>0.05).The relative abundance of Tenericutes at the phylum level increased significantly after prednisone treatment(P<0.05).At the genus level,the relative abundance of Allobaculum increased,while Bifidobacterium,Alloprevotella and Schwartzia decreased after prednisone treatment(P<0.05).Furthermore,the data of PICRUSt showed thatthe activity of endocrine and metabolic pathways,pathways in cancer,metabolism of terpenoids and polyketides,bacterial invasion of epithelial cells,and restriction endonuclease pathways were significantly enhanced than the Control group after prednisone treatment(P<0.05).In contrast,the metabolic pathways related to parasites,lipid metabolism,immune diseases,biodegradation and metabolism of xenobiotics,environmental adaptation,and biosynthesis of other secondary metabolites were weakened comparing to the Control group(P<0.05).Conclusion There were no significant changes in the abundance and diversity of gut microbiota between Control and Prednisone groups.However,the relative abundance of some beneficial bacteria decreased,while Allobaculum increased.The compositional alteration of gut microbiota might be associated with the efficacy and adverse events of prednisone.