首页|粪菌移植对单侧输尿管梗阻小鼠肾脏的保护作用

粪菌移植对单侧输尿管梗阻小鼠肾脏的保护作用

扫码查看
目的:探讨粪菌移植(fecal microbiota transplantation,FMT)对单侧输尿管梗阻(UUO)小鼠肾纤维化的影响.方法:将雄性C57BL/6J小鼠随机分为对照组、UUO组、UUO+FMT组、过继回输髓源抑制性细胞(myeloid-derivedsup-pressorcells,MDSCs)组.后3组通过单侧输尿管结扎构建肾纤维化模型,UUO+FMT组在建立UUO模型后接受来自对照组小鼠的粪菌移植,MDSCs组同时接受脾切除术并静脉注射UUO+FMT组外周血中的MDSCs.术后14 d采集肾组织进行HE、Masson染色;采用实时荧光定量PCR(qRT-PCR)、Western blot法和免疫荧光染色法检测肾组织中TNF-α和IL-10表达水平.结果:HE染色结果显示,对照组小鼠肾组织结构正常;UUO组肾小管显著扩张,伴有明显的炎性细胞浸润;UUO+FMT组和MDSCs组肾脏病变较UUO组明显改善.Masson染色结果显示,与对照组比较,UUO组胶原沉积阳性面积明显增加,而UUO+FMT组和MDSCs组胶原沉积阳性面积较UUO组减少;qRT-PCR、Western blot和免疫荧光结果均显示,与对照组比较,UUO组肾组织中TNF-α、IL-10的表达水平均升高;与UUO组比较,UUO+FMT组和MDSCs组TNF-α表达水平下降而IL-10表达水平升高,差异均有统计学意义.结论:FMT治疗使UUO小鼠肾脏的TNF-α表达减少而IL-10表达增加,并且缓解了肾纤维化,FMT可能通过调控MDSCs发挥肾保护作用.
Protective effect of fecal microbiota transplantation on kidney of mice with unilateral ureteral obstruction
Objective:To investigate the effect of fecal microbiota transplantation(FMT)on unilateral ureteral obstruction(UUO)-induced renal fibrosis in mice.Methods:Male C57BL/6J mice were randomly divided into the control group,UUO group,UUO+FMT group and myeloid-derived suppressor cells(MDSCs)transfer group.The latter 3 groups were constructed renal fibrosis models by UUO,the UUO+FMT group received FMT from control mice after UUO surgery,and the MDSCs transfer group underwent splenectomy and intravenous injection of MDSCs from the peripheral blood of the UUO+FMT group.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.TNF-α and IL-10 expression levels were detected by real-time fluorescence quantitative PCR(qRT-PCR),Western blot and immunofluorescence staining.Results:HE staining showed that the renal tissue structure of the control group was normal.The UUO group showed significant dilatation of renal tubules accompanied by obvious inflammatory cell infiltration.However,the renal lesions in the UUO+FMT group and MDSCs transfer group were significantly improved compared with those in the UUO group.Masson staining showed that the positive area of collagen deposition significantly increased in the UUO group compared with the control group,while the positive area of collagen deposition decreased in the UUO+FMT group and MDSCs transfer group compared with the UUO group.The results of qRT-PCR,Western blot and immunofluorescence showed that the expression levels of TNF-α and IL-10 were elevated in renal tissues of the UUO group compared with the control group.Compared with the UUO group,the expression level of TNF-α decreased while IL-10 increased in the UUO+FMT group and MDSCs transfer group.Conclusions:FMT reduces the expression of TNF-α and increase the expression of IL-10 in the kidney of UUO mice,and alleviates renal fibrosis.FMT may exert a nephroprotective effect by regulating MDSCs.

fecal microbiota transplantationrenal fibrosisureteral obstructionintestinal flora

王雅洁、肖梓豪、曹玉涵

展开 >

皖南医学院弋矶山医院肾内科,安徽 芜湖 241001

皖南医学院麻醉学实验实训中心

粪菌移植 肾纤维化 输尿管梗阻 肠道菌群

2024

沈阳医学院学报
沈阳医学院

沈阳医学院学报

影响因子:0.591
ISSN:1008-2344
年,卷(期):2024.26(3)