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| 蒲公英甾醇经NLRP3炎性小体和肠道菌群改善OVX小鼠骨丢失的机制 |
| Investigate the mechanism of Taraxasterol ameliorates OVX-induced bone loss via NLRP3 inflammasome and gut microbiota |
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| DOI：10.3969/j.issn.1006-7108.2026.06.018 |
| 中文关键词: 蒲公英甾醇 骨质疏松症 NLRP3炎性小体 肠道菌群 |
| 英文关键词:taraxasterol osteoporosis NLRP3 inflammasome gut microbiota |
| 基金项目:广东省中医药管理局项目（20242046）；广州市科技计划项目（2025A03J3723） |
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| 中文摘要: |
| 目的 探讨蒲公英甾醇（Taraxasterol，Tara）抑制NLRP3炎性小体及调节肠道菌群延缓OVX小鼠骨丢失的作用机制。方法 35只雌性C57BL/6J小鼠随机分5组（n=7）：Sham组、OVX组、Tara低（Tara-L）、中（Tara-M）、高（Tara-H）组。连续给药8周后，收集小鼠股骨、血清、结肠和粪便，Micro-CT扫描分析股骨；ELISA检测血清NLRP3炎性小体（Caspase-1、IL-1β和IL-18）及炎性细胞因子（IL-6、TNF-α）；H&E染色观察结肠组织形态，免疫组化染色观察肠紧密连接蛋白Occludin和ZO-1的表达，16S rRNA检测粪便肠道菌群变化。结果 与Sham组相比，OVX组小鼠BMD显著下降（P＜0.001），血清Caspase-1、IL-1β、IL-18、IL-6、TNF-α显著上升（P＜0.001），结肠Occludin和ZO-1表达显著减少（P＜0.001）。与OVX组相比，Tara-L和Tara-M 组BMD有增加趋势（P＞0.05），Tara-H组BMD显著增加（P＜0.05）；Tara-L组血清IL-18降低（P＞0.05），Tara-M、Tara-H组IL-18显著降低（P＜0.01，P＜0.001）；Tara-L、Tara-M、Tara-H各组血清Caspase-1、IL-1β、IL-6、TNF-α显著降低（P＜0.001），且呈剂量依赖性；Occludin在Tara-L、Tara-M组表达增加（P＞0.05），在Tara-H组显著增加（P＜0.01）；ZO-1在Tara-L组表达增加（P＞0.05），在Tara-M、Tara-H组显著增加（P＜0.001）。16S rRNA结果显示，OVX组Ileibacterium、Erysipelotrichaceae、Oscillospiraceae相对丰度显著增加（P＜0.05），Parabacteroides相对丰度显著降低（P＜0.05）；与OVX组比，Tara-H组Ileibacterium、Erysipelotrichaceae、Oscillospiraceae相对丰度显著降低（P＜0.05），Parabacteroides相对丰度有增加趋势（P＞0.05）。结论 Tara能通过抑制NLRP3炎性小体、降低炎性细胞因子和调节肠道菌群结构改善OVX小鼠骨丢失。 |
| 英文摘要: |
| Objective To investigate the mechanism of Taraxasterol (Tara) in inhibiting NLRP3 inflammasome, inflammatory cytokines and regulating gut microbiota to delay bone loss in OVX mice. Methods Thirty-five female C57BL/6J mice were randomly divided into 5 groups (n=7): Sham group, OVX group, Tara low (Tara-L), medium (Tara-M) and high (Tara-H) dose groups. After 8 weeks of continuous administration, the femur, serum, colon and feces of mice were collected. The femur was scanned by Micro-CT. The contents of serum NLRP3 inflammasome (Caspase-1, IL-1β and IL-18) and inflammatory cytokines (IL-6 and TNF-α) were detected by ELISA. The morphology of colon tissue was observed by H&E staining. The expression of colonic tight junction proteins Occludin and ZO-1 ware observed by immunohistochemistry. The changes of gut microbiota were detected by 16S rRNA sequencing. Results Compared with Sham group, the BMD of femur in OVX group was significantly decreased (P<0.001), the levels of serum Caspase-1, IL-1β, IL-18, IL-6 and TNF-α were significantly increased (P<0.001), and the expression of Occludin and ZO-1 in colon was significantly decreased (P<0.001). Compared with OVX group, the BMD of mice in Tara-L and Tara-M group increased (P>0.05), the BMD of mice in Tara-H significantly increased (P<0.05). The serum IL-18 content in the Tara-L group was decreased (P>0.05), and the IL-18 content in the Tara-M and Tara-H groups was significantly decreased (P<0.01, P<0.001). The serum Caspase-1, IL-1β, IL-6 and TNF-α contents in the Tara-L, Tara-M and Tara-H groups were significantly decreased (P<0.001), and showed a dose-dependent manner. The expression of Occludin was increased in Tara-L and Tara-M groups(P>0.05), significantly increased in Tara-H group (P<0.05), and ZO-1 was increased in Tara-L group (P>0.05), significantly increased in Tara-M and Tara-H groups (P<0.001). The results of 16S rRNA showed that the relative abundance of Ileibacterium, Erysipelotrichaceae and Oscillospiraceae in the OVX group increased significantly (P<0.05), the relative abundance of Parabacteroides significantly decreased (P<0.05). Compared with OVX group, the relative abundance of Ileibacterium, Erysipelotrichaceae and Oscillospiraceae in Tara-H group was significantly decreased (P<0.05), the relative abundance of Parabacteroides increased (P>0.05). Conclusion Tara can inhibit NLRP3 inflammasome, reduce inflammatory cytokines and regulate gut microbiota to improve bone loss in OVX mice. |
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