中国骨质疏松杂志

异钩藤碱调节氧化应激和肠道菌群抑制去卵巢小鼠骨丢失机制研究

Mechanism of isorhynchophylline in inhibiting bone loss in OVX mice via regulation of oxidative stress and gut microbiota

DOI：10.3969/j.issn.1006-7108.2026.09.010

中文关键词: 异钩藤碱骨质疏松症去卵巢小鼠氧化应激肠道菌群

英文关键词:isorhynchophylline osteoporosis ovariectomized mice oxidative stress gut microbiota

基金项目:广州市科技计划项目（2025A03J3723）；广东省中医药局科研项目（20242046）

作者	单位
雷艺陶1 梁施慧2 刘艳铭1 周怡琳1 张颖童1 李诗梅1 赵晓3 董群伟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 510062 2.广州市越秀区黄花岗街道社区卫生服务中心,广东广州 510075 3.广州中医药大学,广东广州 510006

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中文摘要:

目的探究异钩藤碱（isorhynchophylline，IRN）调节氧化应激和肠道菌群抑制去卵巢（OVX）小鼠骨丢失机制。方法 28只C57BL/6J雌鼠随机分为假手术组（Sham）、OVX组、IRN低剂量组[IRN-L，10 mg/（kg·d）]和IRN高剂量组[IRN-H，20 mg/（kg·d）]，实验期8周。Micro-CT分析BMD、BV/TV、Tb.N、Tb.Th和Tb.Sp；ELISA法检测TRACP5b、β-CTX、P1NP、BALP、TNF-α、IL-1β、IL-6、IL-10、NO、iNOS和ROS；16S rRNA测序分析肠道菌群；GC-MS测定短链脂肪酸；免疫组化评估结肠紧密连接蛋白ZO-1、Claudin-1和Occludin。结果 OVX组小鼠BMD、BV/TV、Tb.N、Tb.Th和IL-10较Sham组显著降低（P＜0.01，P＜0.001），Tb.Sp、TRACP5b、β-CTX、P1NP、BALP、TNF-α、IL-1β、IL-6、NO、iNOS和ROS显著增高（P＜0.001）；IRN-L组和IRN-H组BMD、BV/TV、Tb.N和IL-10较OVX组显著增高（P＜0.05，P＜0.01，P＜0.001），Tb.Sp、TRACP5b、β-CTX、P1NP、BALP、TNF-α、IL-1β、IL-6、NO、iNOS和ROS显著降低（P＜0.05，P＜0.01，P＜0.001）；IRN-H组Tb.Th较OVX组显著增高（P＜0.05）；OVX组Campilobacterota和Helicobacter丰度较Sham组呈上升趋势（P＞0.05），IRN-H组较OVX组丰度均显著降低（P＜0.05）；OVX组丁酸水平较Sham组显著降低（P＜0.05），IRN-H组较OVX组显著升高（P＜0.05）；OVX组紧密连接蛋白ZO-1、Claudin-1和Occludin表达较Sham组显著降低（P＜0.001），IRN-L组和IRN-H组较OVX组显著升高（P＜0.01，P＜0.001）。结论 IRN可能通过缓解炎症反应和氧化应激、调节肠道菌群和短链脂肪酸以及修复肠道屏障抑制OVX小鼠骨丢失。

英文摘要:

Objective To investigate the mechanism of isorhynchophylline (IRN) in inhibiting bone loss in ovariectomized (OVX) mice through regulating oxidative stress and gut microbiota. Methods Twenty-eight C57BL/6J female mice were randomly assigned to four groups: Sham group (Sham), OVX group, IRN low-dose group (IRN-L, 10mg·kg-1·d-1), and IRN high-dose group (IRN-H, 20mg·kg-1·d-1). The experiment lasted for 8 weeks. BMD, BV/TV, Tb.N, Tb.Th, and Tb.Sp were analyzed using micro-CT. Serum levels of TRACP5b, β-CTX, PINP, BALP, TNF-α, IL-1β, IL-6, IL-10,NO, iNOS, and ROS were measured using ELISA. Gut microbiota composition was assessed with 16S rRNA sequencing, while short-chain fatty acids (SCFAs) were quantified via GC-MS. Immunohistochemistry was performed to evaluate colonic tight junction proteins (ZO-1, Claudin-1, and Occludin). Results Compared to Sham group, OVX group showed significant decreases in the levels of BMD, BV/TV, Tb.N, Tb.Th, and IL-10 (P<0.01, P<0.001), while the levels of Tb.Sp, TRACP5b, β-CTX, PINP, BALP, TNF-α, IL-1β, IL-6, NO, iNOS, and ROS increased significantly in OVX group (P<0.001). Compared to OVX group, both IRN-L and IRN-H group exhibited significant increase in the levels of BMD, BV/TV, Tb.N, and IL-10 (P<0.05, P<0.01, P<0.001), along with significant decrease in the levels of Tb.Sp, TRACP5b, β-CTX, PINP, BALP, TNF-α, IL-1β, IL-6, NO, iNOS, and ROS (P<0.05, P<0.01, P<0.001). Tb.Th in IRN-H group was significantly higher than that in OVX group (P<0.05). The abundances of Campilobacterota and Helicobacter showed an increasing trend in OVX group compared to Sham group (P>0.05), and their abundances were significantly reduced in IRN-H group compared to OVX group (P<0.05). The level of butanoic acid decreased significantly in OVX group compared to that in Sham group (P<0.05), and significantly increased in IRN-H group compared to that in OVX group (P<0.05). Furthermore, the expression levels of the tight junction proteins ZO-1, Claudin-1, and Occludin reduced significantly in OVX group compared to those in Sham group (P<0.001), and significantly elevated in both IRN-L and IRN-H groups compared to OVX group (P<0.01, P<0.001). Conclusion IRN may inhibit bone loss in OVX mice by alleviating inflammatory response and oxidative stress, regulating gut microbiota and SCFAs, and repairing intestinal barrier.

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