牛蒡子苷经炎性因子和肠道菌群抑制钛颗粒诱导骨溶解的机制  

The mechanism of inhibition of titanium partical-induced osteolysis by ARC through inflammatory factors and gut microbiota

作　　者：唐琳 谢佑红 周天宇 周怡琳 葛冬冬 王姜俨 董群伟 孙平[1] TANG Lin;XIE Youhong;ZHOU Tianyu;ZHOU Yilin;GE Dongdong;WANG Jiangyan;DONG Qunwei;SUN Ping(Department of Endocrinology,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510006,China;Department of Orthopedics,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510006,China;Department of Orthopedics,Yunfu Hospital of Traditional Chinese Medicine,Yunfu 527300,China)

机构地区：[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骨科,广东云浮527300

出　　处：《中国骨质疏松杂志》2024年第6期847-852,共6页Chinese Journal of Osteoporosis

基　　金：广东省云浮市科技计划项目(2020A090402)。

摘　　要：目的基于炎性因子和肠道菌群的变化,探讨牛蒡子苷(ARC)抑制钛颗粒诱导小鼠颅骨周围骨溶解的机制。方法20只7周龄C57BL/6J雌性小鼠被随机均匀分配到以下组:空白组(SHAM)、骨溶解模型组(Vehicle)、ARC低剂量组(L-ARC)以及ARC高剂量组(H-ARC),每组5只。L-ARC、H-ARC组在Vehicle组基础上分别给予5、10 mg/(kg·d)ARC腹腔注射,SHAM组和Vehicle组腹腔注射等剂量生理盐水,每日1次,共14 d。通过Micro-CT测定小鼠颅骨BMD、BV/TV、Tb.N、BS/BV、Tb.Sp和Tb.Th;ELISA法检测小鼠血清中TRACP5b、CTX、OCN、IL-6、TNF-α和IL-10水平;16S rRNA高通量测序技术分析粪便中菌群结构与丰度变化。结果Vehicle组BMD、BV/TV、Tb.N、BS/BV、Tb.Th、OCN和IL-10较SHAM组显著降低(P<0.01,P<0.05),Tb.Sp、TRACP5b、CTX、IL-6和TNF-α显著升高(P<0.05,P<0.01);L-ARC组BMD、BV/TV、Tb.N、BS/BV、Tb.Th和OCN较Vehicle组有升高趋势(P>0.05),Tb.Sp、TRACP5b和CTX有降低趋势(P>0.05),TNF-α和IL-6显著降低(P<0.05),IL-10显著升高(P<0.05);H-ARC组BMD、BV/TV、Tb.N和IL-10较Vehicle组显著升高(P<0.05,P<0.01),TRACP5b、CTX、IL-6和TNF-α显著降低(P<0.05,P<0.01),BS/BV、Tb.Th和OCN有升高趋势(P>0.05),Tb.Sp有降低趋势(P>0.05)。在门水平,Vehicle组Firmicutes/Bacteroidota(F/B)率较SHAM组有升高趋势(P>0.05);L-ARC和H-ARC组F/B率较Vehicle组显著降低(P<0.01)。在属水平,Vehicle组Ileibacterium丰度较SHAM组有升高趋势(P>0.05),Prevotellaceae_UCG-001和Rikenellaceae_RC9_gut_group丰度有降低趋势(P>0.05);较Vehicle组,经ARC干预后,Ileibacterium丰度显著降低(P<0.05),Prevotellaceae_UCG-001和Rikenellaceae_RC9_gut_group丰度显著增加(P<0.05)。结论ARC可通过抑制炎性反应、调节肠道菌群结构抑制钛颗粒诱导的小鼠颅骨骨溶解,且呈剂量依赖性。Objective To investigate the mechanism of inhibiting titanium partical-induced osteolysis around the skull with arctiin(ARC)in mice based on the changes of inflammatory factors and gut microbiota.Methods Twenty 7-week-old C57BL/6J female mice were randomly and evenly assigned to the following groups:blank group(SHAM),model group(Vehicle),ARC low-dose group,(L-ARC)and ARC high-dose group(H-ARC).During the following 14 days,mice in the experimental group were injected intraperitoneally with two different concentrations of ARC[5 and 10 mg/(kg·d)],respectively.Mice in the sham group and vehicle group were injected with 0.9%NaCl every day.The following parameters of skulls,BMD,BV/TV,Tb.N,BS/BV,Tb.Sp,and Tb.Th were detected with micro-CT.The levels of TRACP5b,CTX,OCN,IL-6,TNF-α,and IL-10 in serum were detected with ELISA.16 S rRNA sequencing was used to analyze the structure and abundance of gut microbiota.Results BMD,BV/TV,Tb.N,BS/BV,Tb.Th,OCN,and IL-10 decreased significantly in Vehicle group compared to those in SHAM group(P<0.01,P<0.05).Tb.Sp,TRACP5b,CTX,IL-6,and TNF-αsignificantly increased(P<0.05,P<0.01).Compared to those in Vehicle group,BMD,BV/TV,Tb.N,BS/BV,Tb.Th,and OCN in L-ARC group had an increasing trend(P>0.05),Tb.Sp,TRACP5b,and CTX had a decreasing trend(P<0.05),TNF-αand IL-6 significantly decreased(P<0.05),and IL-10 significantly increased(P<0.05).Compared to those in Vehicle group,the levels of BMD,BV/TV,Tb.N,and IL-10 in H-ARC group significantly increased(P<0.05,P<0.01),the levels of TRACP5b,CTX,IL-6,and TNF-αsignificantly decreased(P<0.05,P<0.01),while the levels of BS/BV,Tb.Th,and OCN had an increasing trend(P>0.05),and Tb.Sp had a decreasing trend(P>0.05).At the phylum level,compared to that in SHAM group,firmicutes/bacteroidota(F/B)ratio had an increasing trend in Vehicle group(P>0.05).However,compared to that in Vehicle group,the F/B ratio in L-ARC and H-ARC groups significantly decreased(P<0.01).At the genus level,compared to that in SHAM group,the abundance of ileibacterium in Vehicle gro

关 键 词：无菌性假体松动 钛颗粒 骨溶解 牛蒡子苷 炎性因子 肠道菌群 

分 类 号：R68[医药卫生—骨科学]