肠道菌群介导贞术调脂胶囊抑制去势小鼠骨丢失的机制研究
Study on the Mechanism of FTZ on bone loss in ovariectomized mice via gut microbiota
  
DOI:10.3969/j.issn.1006-7108.2022.12.017
中文关键词:  骨质疏松症  肠道菌群  去卵巢小鼠  贞术调脂胶囊
英文关键词:osteoporosis  gut microbiota  ovariectomized mice  ZhenzhuTiaozhi Capsule
基金项目:广东省云浮市科技计划项目(2020A090402);广东省中医药局科研项目(20192044);广东省中医药局科研项目(20222120);国家自然科学基金项目(青年科学基金)(81704098)
作者单位
王姜俨1# 胡丽1# 董群伟2,3 唐琳1 葛冬冬2 卢秉慧4 周天宇1 谢佑红1 孙平1* 1广东药科大学附属第一医院内分泌科广东 广州 510006 2广东药科大学附属第一医院骨科广东 广州 510006 3广东省云浮市中医院广东 云浮 527300 4广东药科大学附属第一医院中医科广东 广州 510006 
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中文摘要:
      目的 基于肠道菌群的变化,探讨贞术调脂胶囊(FTZ)抑制去卵巢(OVX)小鼠骨丢失的作用机制。方法选取18只11周C57BL6/J雌性小鼠,平均分为假手术组(SHAM组)、OVX组和FTZ组。FTZ组在OVX基础上给予FTZ[1.55 g/(kg·d)]灌胃,SHAM组和OVX组以等剂量0.9%氯化钠溶液灌胃,12周后收集小鼠左侧股骨、血清和粪便标本。左侧股骨行Micro-CT扫描;采用ELISA法检测血清中TNF-α、IL-10、IL-6、LPS和TRACP5b的含量;末次灌胃结束24 h后收集小鼠粪便,提取并检测粪菌总DNA,利用16S rRNA高通量肠菌基因测序技术,对标本中的细菌16S rRNA 基因V3-V4可变区进行定性分析和OUT分析。结果 与SHAM组相比,OVX组BV/TV、Tb.N、BMD和IL-10均显著性降低(P<0. 05),Tb.Sp、TNF-α、IL-6、LPS和TRACP5b显著性增高(P<0. 05);与OVX组相比,FTZ组Tb.N和IL-10显著性增高(P<0. 05),Tb.Sp、TNF-α、IL-6和TRACP5b显著性降低(P<0. 05)。在门水平,OVX组Firmicutes/Bacteroidota(F/B)率较SHAM组有增高趋势(P=0.310),但无显著性差异,而与OVX组相比,FTZ组F/B率显著性降低(P=0.002)。在属水平,与SHAM组相比,Faecalibaculum和Coriobacteriaceae_UCG-002丰度在OVX组中显著减少(P=0.030,P=0.005),Lachnoclostridium丰度在OVX组中显著增加(P=0.037),而与OVX组相比,FTZ组Faecalibaculum和Coriobacteriaceae_UCG-002丰度显著增加(P =0.045,P=0.005),Lachnoclostridium丰度显著减少(P=0.013)。结论 FTZ能够延缓去势小鼠骨量丢失,其机制可能是通过调节肠道菌群中Faecalibaculum、Coriobacteriaceae_UCG-002和Lachnoclostridium丰度实现的,且同时抑制炎性反应。
英文摘要:
      Objective To investigate the regulatory mechanism of FTZ inhibiting bone loss in ovariectomized (OVX) mice based on the changes of gut microbiota. Methods Eighteen 11-week-old C57BL6/J female mice were randomly divided into three groups: SHAM group (n=6) and OVX group (n=6) received an equal dose of 0.9% NaCl in the same manner; FTZ group (n=6) received FTZ at a dose of 1.55 g/kg/d via oral gavage. After 12 weeks of intervention, the outcomes were changes in bone microstructures as measured by Micro-CT scanning analysis, serum parameters (TNF-α, IL-10, IL-6, LPS and TRACP5b) and gut microbiota were measured by ELISA and 16S rRNA sequencing respectively. Results Compared with SHAM group, BV/TV, Tb.N, BMD and concentration of IL-10 were significantly decreased (P<0.05); Tb.Sp and concentration of TNF-α, IL-6, LPS and TRACP5b were significantly increased (P<0.05) in OVX group. The Tb.N and IL-10 were significantly increased (P<0.05), Tb.Sp, TNF-α, IL-6 and TRACP5b were significantly decreased in FTZ group compared with OVX group (P<0.05). At the phylum level, there was an increasing trend in F/B ratio (P =0.310) in OVX group compared with SHAM group. F/B ratio was significantly lower in FTZ group compared with OVX group (P=0.002). At the genus level, Faecalibaculum and Coriobacteriaceae_UCG-002 were significantly decreased (P=0.030, P=0.005) and Lachnoclostridium was significantly increased (P=0.037) in OVX group compared with SHAM group. Faecalibaculumand and Coriobacteriaceae_UCG-002 were significantly increased (P=0.045, P=0.005) and Lachnoclostridium was significantly decreased (P=0.013) in FTZ group. Conclusions FTZ can alleviate bone loss in OVX mice may be achieved by regulating the abundance of Faecalibaculum, Coriobacteriaceae_UCG-002 and Lachnoclostridium, meanwhile ameliorating the inflammatory response.
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