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
  
DOI:10.3969/j.issn.1006-7108.2024.06.012
中文关键词:  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
英文关键词:aseptic prosthesis loosening  titanium particle  osteolysis  arctiin  inflammatory factor  gut microbiota
基金项目:广东省云浮市科技计划项目(2020A090402)
作者单位
唐琳1 谢佑红1 周天宇1 周怡琳1 葛冬冬2 王姜俨1 董群伟2,3 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骨科 广东 云浮 527300 
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中文摘要:
      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。
英文摘要:
      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. 16S 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-α significantly 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-α and 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-α significantly 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 group had an increasing trend (P>0.05), the abundance of prevotellaceae_UCG-001 and rikenellaceae_RC9 in gut in Vehicle group had a decreasing trend (P>0.05). While compared to that in Vehicle group, the abundance of ileibacterium in ARC groups significantly decreased (P<0.05), the abundance of prevotellaceae UCG-001 and rikenellaceae RC9 in gut in ARC groups significantly increased (P<0.05). Conclusion ARC inhibits titanium partical-induced osteolysis in mice by suppressing inflammation and modulating the structure of gut microbiota in a dose-dependent manner.
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