基于“肠-骨轴”理论探讨艾灸对骨质疏松模型大鼠肠道菌群的影响
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成都中医药大学针灸推拿学院

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国家自然科学基金(82105027);四川省自然科学基金面上项目(2024NSFSC0729、2022NSFSC0857);针灸防治老年疾病教育部重点实验室Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education


Effects of Moxibustion on Gut Microbiota in a Rat Model of Ovariectomy-Induced Osteoporosis Based on the “Gut–Bone Axis” Theory
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1.School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine;2.School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine,

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    摘要:

    目的:观察艾灸对去卵巢骨质疏松(Osteoporosis,OP)模型大鼠骨代谢、肠道菌群(Gut microbiota,GM)及短链脂肪酸(Short-chain fatty acids,SCFAs)的影响,探讨其改善OP的潜在机制。方法:将24只9周龄雌性SD大鼠,采用随机数字表法随机分为假手术组(Sham组,8只)和手术组(16只),手术组行双侧卵巢切除术造模后采用随机数表法分为模型组(Model组)、模灸组(Moxi组),每组8只。Moxi组每日对双侧“脾俞”和“足三里”穴施灸治疗20 min连续8周;Sham组、Model组不予干预。干预结束后,采集大鼠胫骨组织、血液及肠道内容物标本,用HE染色观察胫骨组织形态;ELISA法测定血清骨碱性磷酸酶、骨钙素、I型前胶原氨基端原肽及雌二醇水平;16S rRNA高通量测序分析肠道菌群多样性及结构变化;液相色谱-质谱联用技术(Liquid Chromatograph-Mass Spectrometer,LC-MS)对肠道内容物中SCFAs进行靶向定量分析。结果:与Sham组比较,Model组大鼠体重增长速率明显加快(P < 0.001),血清骨代谢相关指标水平显著降低(P < 0.001),胫骨骨小梁稀疏、断裂,骨髓腔内脂肪空泡增多;肠道菌群结构发生紊乱,厚壁菌门/拟杆菌门(Firmicutes/Bacteroidetes,F/B)比值异常升高,β多样性明显改变,SCFAs代谢谱异常。与Model组比较,艾灸干预后大鼠体重异常增长受到抑制(P < 0.001),血清骨代谢指标水平明显回升(P < 0.001),骨微结构及骨髓脂肪浸润情况显著改善;肠道菌群结构得到重塑,F/B比值显著降低,异普雷沃氏菌属等特征菌群富集,SCFAs代谢紊乱得到一定回调,整体代谢谱趋近Sham组。结论:艾灸可改善去卵巢性OP大鼠骨微结构损伤及骨代谢异常,并伴随肠道菌群结构及SCFAs代谢谱的调整,提示其骨保护效应可能与“肠-骨轴”相关,但具体因果机制尚需进一步实验验证。

    Abstract:

    Objective:To observe the effects of moxibustion on bone metabolism, gut microbiota (GM), and short-chain fatty acids (SCFAs) in ovariectomy-induced osteoporosis (OP) model rats, and to explore its potential mechanisms in improving OP.Methods:Twenty-four nine?week?old female Sprague–Dawley rats were randomly divided using a random number table into a sham operation group (Sham,?n?=?8) and a surgical group (n?=?16). Rats in the surgical group underwent bilateral ovariectomy to establish an osteoporosis (OP) model. After successful modeling, they were further randomized into a model group (Model,?n?=?8) and a moxibustion group (Moxi,?n?=?8). The Moxi group received daily moxibustion at bilateral “Pishu” and “Zusanli” acupoints for 20?minutes over eight consecutive weeks, while the Sham and Model groups received no intervention.After the intervention, tibial tissues, blood samples, and intestinal contents were collected. Histological morphology of the tibia was observed by hematoxylin–eosin (HE) staining. Serum levels of bone alkaline phosphatase (BALP), osteocalcin (BGP), procollagen?I?N?terminal propeptide (PINP), and estradiol (E2) were determined by enzyme?linked immunosorbent assay (ELISA). High-throughput 16S rRNA sequencing was performed to analyze the diversity and structural changes of the gut microbiota.Liquid chromatography–mass spectrometry (LC-MS) was used for targeted quantitative analysis of SCFAs in intestinal contents.Results: Compared with the Sham group, rats in the Model group showed a significantly accelerated rate of body weight gain (P <0.001), markedly decreased serum levels of bone metabolism-related indicators (P <0.001), sparse and fractured trabeculae in the tibia, and increased fat vacuoles in the bone marrow cavity. In addition, the gut microbiota was disrupted, with an abnormally elevated Firmicutes/Bacteroidetes (F/B) ratio,significantly altered beta diversity, and an abnormal SCFAs metabolic profile. Compared with the Model group, moxibustion intervention significantly inhibited abnormal body weight gain in rats (P <0.001), markedly restored serum bone metabolism-related indicators (P <0.001), and significantly improved bone microstructure and bone marrow fat infiltration. Meanwhile, the gut microbiota structure was remodeled, the F/B ratio was significantly reduced, characteristic taxa such as Alloprevotella were enriched, SCFAs metabolic disturbances were partially reversed, and the overall metabolic profile tended to approach that of the Sham group.Conclusion:Moxibustion can improve bone microstructural damage and bone metabolism abnormalities in ovariectomy-induced OP rats, accompanied by alterations in gut microbiota structure and SCFAs metabolic profiles. These findings suggest that its bone-protective effect may be associated with the “gut-bone axis,” although the specific causal mechanisms require further experimental verification.

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  • 收稿日期:2026-03-08
  • 最后修改日期:2026-06-07
  • 录用日期:2026-09-01
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