摘要
目的:运用16S rRNA基因测序技术探讨博来霉素诱导的系统性硬化病(SSc)模型小鼠肠道菌群改变及醋酸泼尼松龙的干预作用。方法:博来霉素诱导建立SSc小鼠模型,醋酸泼尼松龙干预治疗28 d,设正常对照组。观察各组小鼠生存状态,天狼星染色观察组织病理改变及检测胶原纤维含量。利用16S rRNA基因测序技术对各组小鼠粪便DNA进行肠道菌群高通量测序分析。结果:与对照组比较,模型组小鼠出现精神萎靡,背部皮肤变硬、结痂,粘连皮下组织,皮肤及肺组织胶原纤维含量明显增多(P<0.01);肠道菌群物种丰度、谱系多样性降低(P<0.05);菌群结构发生显著变化,普雷沃氏菌科、普雷沃氏菌科_UCG-001、乳杆菌属、拟杆菌属丰度显著降低(P<0.05);螺杆菌、文肯菌属、瘤胃梭菌属_6、罗斯氏菌属、瘤球菌科_UCG-005丰度显著升高(P<0.05)。与模型组比较,醋酸泼尼松龙治疗组改善了SSc小鼠生存状态,明显下调皮肤及肺组织胶原纤维含量(P<0.01);增加了肠道菌群物种丰度及谱系多样性,但差异无统计学意义(P>0.05);逆转了普雷沃氏菌科、文肯菌属、瘤球菌科_UCG-005丰度变化趋势(P<0.05)。结论:博来霉素诱导的SSc小鼠肠道不同分类水平细菌丰富度、谱系多样性及菌群结构明显改变。SSc主要治疗药物糖皮质激素(GCs)醋酸泼尼松龙有限度地影响了SSc小鼠肠道菌群,但改善作用不明显。
Objective:To explore changes of intestinal microbiota in bleomycin-induced mice model of systemic sclerosis(SSc)and interventional effects of prednisolone acetate using 16S rRNA gene-sequencing technology.Methods:Mice models of SSc were established by bleomycin induction,and treated with prednisolone acetate for 28 days,a normal control group was set.Survival status,histopathological changes by Sirius red staining and collagen fiber content of mice in each group were observed.High-throughput sequencing analysis of intestinal microbiota was performed on DNA from feces of mice in each group by 16S rRNA gene-sequencing technology.Results:Compared with Control group,mice in Model group were listlessness,back skin became hard,crusted and adhered to subcutaneous tissues,contents of collagen fibers in skin and lung tissues were increased significantly(P<0.01);species richness and lineage diversity of intestinal microbiota were decreased(P<0.05);microbiota structure changed significantly,and abundance of Prevotellaceae,Prevotellaceae_UCG-001,Lactobacillus and Bacteroides were decreased significantly(P<0.05);abundances of Helicobacter,Rikenella,Ruminiclostridium_6,Roseburia and Ruminococcaceae_UCG-005 were significantly increased(P<0.05).Compared with Model group,prednisolone acetate treatment group improved survival status of SSc mice;contents of collagen fibers were down-regulated significantly in skin and lung tissues(P<0.01);species richness and lineage diversity of intestinal microbiota was increased,but with no statistically significant difference(P>0.05);abundance trends of Prevotellaceae,Rikenella and Ruminococ⁃caceae_UCG-005 were reversed(P<0.05).Conclusion:SSc induced by bleomycin can cause significant changes in bacterial abundance,lineage diversity and bacterial community structure of different taxonomic levels in mice intestinal microbiota.Prednisolone acetate,main treatment drug for SSc,a kind of glucocorticoids(GCs),improves intestinal microbiota of mice with SSc to a limited extent,but effects are not obvious.
作者
张羽
周雪艳
赵亮娟
李凯
吕军影(指导)
ZHANG Yu;ZHOU Xueyan;ZHAO Liangjuan;LI Kai;LYU Junying(First Clinic Medicine of Guangxi Medical University,Nanning 530021,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第11期2255-2264,共10页
Chinese Journal of Immunology
基金
广西自然科学基金重点项目(2018GXNSFDA281047)
广西中医药重点学科建设项目(GZXK-Z-20-52)。
