[1]刘华忠,香世宝,刘博,等.基于态靶理论探讨肠道菌群失调在骨质疏松症发生发展中的作用机制及中医药干预策略[J].中医正骨,2026,38(07):81-87.
 LIU Huazhong,XIANG Shibao,LIU Bo,et al.Exploring the mechanisms of gut microbiota dysbiosis in the onset and progression of osteoporosis and its TCM-based therapeutic strategies based on the state-target theory[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2026,38(07):81-87.
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基于态靶理论探讨肠道菌群失调在骨质疏松症发生发展中的作用机制及中医药干预策略()

《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第38卷
期数:
2026年07期
页码:
81-87
栏目:
学术探讨
出版日期:
2026-07-20

文章信息/Info

Title:
Exploring the mechanisms of gut microbiota dysbiosis in the onset and progression of osteoporosis and its TCM-based therapeutic strategies based on the state-target theory
作者:
刘华忠1; 香世宝1; 刘博1; 丁龙龙1; 张涵隽1; 张桂鑫2; 王博2; 龚春柱2
1.广州中医药大学,广东 广州 510006; 2.深圳平乐骨伤科医院/深圳市坪山区中医院,广东 深圳 518118
Author(s):
LIU Huazhong; XIANG Shibao; LIU Bo; DING Longlong; ZHANG Hanjun; ZHANG Guixin; WANG Bo; GONG Chunzhu
关键词:
骨质疏松;  胃肠道微生物群;  生态失调;  肠道屏障功能;  态靶理论;  作用机制;  中医药疗法;  综述
摘要:
骨质疏松症(osteoporosis,OP)是临床常见的全身性代谢性骨病。近年来研究发现,肠道菌群可通过调控肠道屏障功能、免疫炎症反应、菌群代谢产物及雌激素代谢等多条途径影响骨代谢稳态,已成为干预OP的潜在靶点。然而,肠道菌群失调与OP病机演变之间的内在联系尚待系统阐释。态靶理论强调宏观病态辨识与微观靶点干预相结合,为阐释OP的发病机制、探寻中医药干预策略提供了新的视角。本文基于态靶理论,梳理了OP“正虚态-瘀滞态-毒损态”的病机演变规律,阐释了各病态与肠道菌群失调的关联,分析了肠道菌群失调在OP发生发展中的作用机制,提出了中医药调节肠道菌群干预OP的策略,为中医药防治OP提供了新的思路与参考。

参考文献/References:

[1] 中华医学会骨质疏松和骨矿盐疾病分会.中国骨质疏松症流行病学调查及“健康骨骼”专项行动结果发布[J].中华骨质疏松和骨矿盐疾病杂志,2019,12(4):317-318.
[2] TICINESI A,SINISCALCHI C,MESCHI T,et al.Gut microbiome and bone health:update on mechanisms,clinical correlations,and possible treatment strategies[J].Osteoporos Int,2025,36(2):167-191.
[3] 仝小林,何莉莎,赵林华.论“态靶因果”中医临床辨治方略[J].中医杂志,2015,56(17):1441-1444.
[4] 何莉莎,宋攀,赵林华,等.态靶辨证——中医从宏观走向精准的历史选择[J].辽宁中医杂志,2020,47(1):1-4.
[5] 黄振,李威,叶佰盛,等.由“虚瘀毒”理论探析细胞焦亡与骨质疏松的关联[J].中国骨质疏松杂志,2025,31(2):278-282.
[6] 王伟,万雷,柴爽,等.骨质疏松症的中医病因病机和分期治疗[J].中医正骨,2018,30(2):29-30.
[7] 史晓林,梁博程,李春雯.从“因虚致瘀”论原发性骨质疏松症病机[J].中国中西医结合杂志,2019,39(1):111-114.
[8] 蒋欣,杨小龙,张泽臣,等.由“虚瘀”理论探讨耆鹿逐痹胶囊防治肾虚血瘀型骨质疏松的作用[J].中国骨质疏松杂志,2024,30(6):880-883.
[9] 邹秀淇,郑承红,李云海,等.从“虚、痰、瘀、毒”分期论治糖尿病性骨质疏松症[J].中国骨质疏松杂志,2024,30(12):1787-1790.
[10] 刘馥溧,巴元明.巴元明从虚瘀毒论治肾性骨质疏松症的经验[J].中国中医骨伤科杂志,2024,32(1):85-87.
[11] HE Y,CHEN Y.The potential mechanism of the microbiota-gut-bone axis in osteoporosis:a review[J].Osteoporos Int,2022,33(12):2495-2506.
[12] 周志城,田瀚,庄旭锐,等.不同中医证型骨质疏松症患者肠道菌群的差异性分析[J].广州中医药大学学报,2024,41(9):2289-2295.
[13] ROPOTHSCHILD D,WEISSBROD O,BARKAN E,et al.Environment dominates over host genetics in shaping human gut microbiota[J].Nature,2018,555(7695):210-215.
[14] 董恩钊,冯学烽,李学圆,等.基于16SrRNA序列分析脾虚证骨质疏松症患者肠道菌群分布特点[J].广州中医药大学学报,2024,41(8):1947-1955.
[15] 丁维俊,高峰,杨杰,等.肾阳虚证患者肠道菌群失调状况的临床研究[J].新中医,2007,39(1):9-10.
[16] 张欢,周莹莹,于游,等.基于TMA/FMO3/TMAO信号通路探讨清脂通脉颗粒对膏脂转输障碍大鼠肠道微生态的调控机制[J].中华中医药学刊,2020,38(10):134-137.
[17] 陈浩,李甲,胡蕾,等.基于Sirt1-FXR通路探究京尼平苷酸对胆汁淤积大鼠胆汁酸肝肠循环的影响[J].中国中药杂志,2019,44(4):787-795.
[18] TONG L,FENG Q,LU Q,et al.Combined 1H NMR fecal metabolomics and 16S rRNA gene sequencing to reveal the protective effects of Gushudan on kidney-yang-deficiency-syndrome rats via gut-kidney axis[J].J Pharm Biomed Anal,2022,217:114843.
[19] FENG B,LU J,HAN Y,et al.The role of short-chain fatty acids in the regulation of osteoporosis:new perspectives from gut microbiota to bone health:a review[J].Medicine(Baltimore),2024,103(34):e39471.
[20] LIN Y H,LIAN W S,WU R W,et al.Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding[J].Cell Mol Life Sci,2024,82(1):13.
[21] CHEN Y,YANG C,DAI Q,et al.Gold-nanosphere mitigates osteoporosis through regulating TMAO metabolism in a gut microbiota-dependent manner[J].J Nanobiotechnology,2023,21(1):125.
[22] LYU Z,HU Y,GUO Y,et al.Modulation of bone remodeling by the gut microbiota:a new therapy for osteoporosis[J].Bone Res,2023,11(1):31.
[23] GAWALKO M,AGBAEDENG T A,SALJIC A,et al.Gut microbiota,dysbiosis and atrial fibrillation.Arrhythmogenic mechanisms and potential clinical implications[J].Cardiovasc Res,2022,118(11):2415-2427.
[24] MA Z,LIU Y,SHEN W,et al.Osteoporosis in postmeno-pausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells[J].BMC Musculoskelet Disord,2024,25(1):791.
[25] GRÜNER N,ORTLEPP A L,MATTNER J.Pivotal role of intestinal microbiota and intraluminal metabolites for the maintenance of gut-bone physiology[J].Int J Mol Sci,2023,24(6):5161.
[26] GUO M,LIU H,YU Y,et al.Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure[J].Gut Microbes,2023,15(1):2190304.
[27] ALQRANEI M S,SENBANJO L T,ALJOHANI H,et al.Lipopolysaccharide-TLR-4 axis regulates osteoclastogenesis independent of RANKL/RANK signaling[J].BMC Immunol,2021,22(1):23.
[28] YU M,PAL S,PATERSON C W,et al.Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells[J].J Clin Invest,2021,131(4):e143137.
[29] PENG R,SONG C,GOU S,et al.Gut Clostridium sporogenes-derived indole propionic acid suppresses osteoclast formation by activating pregnane X receptor[J].Pharmacol Res,2024,202:107121.
[30] MCCABE L R,PARAMESWARAN N.Advances in probiotic regulation of bone and mineral metabolism[J].Calcif Tissue Int,2018,102(4):480-488.
[31] XIANG T,DENG Z,YANG C,et al.Bile acid metabolism regulatory network orchestrates bone homeostasis[J].Pharmacol Res,2023,196:106943.
[32] HANSDAH K,LUI J C.Emerging insights into the endocrine regulation of bone homeostasis by gut microbiome[J].J Endocr Soc,2024,8(8):bvae117.
[33] HU S,DING Q,ZHANG W,et al.Gut microbial beta-glucuronidase:a vital regulator in female estrogen metabolism[J].Gut Microbes,2023,15(1):2236749.
[34] BAKER J M,AL-NAKKASH L,HERBST-KRALOVETZ M M.Estrogen-gut microbiome axis:physiological and clinical implications[J].Maturitas,2017,103:45-53.
[35] 阮璐薇,张鹏横,胡柳,等.肠道菌群与绝经后骨质疏松症雌激素介导骨免疫失衡的相关性研究[J].中华中医药杂志,2020,35(2):820-823.
[36] 李伟举,陈晓聪,曾家莹,等.参骨颗粒通过肠道菌群改善骨质疏松的研究[J].中国骨质疏松杂志,2024,30(9):1341-1347.
[37] 周志城.基于肠道菌群论治补肾调肝方治疗骨质疏松的临床疗效[D].广州:广州中医药大学,2024.
[38] LI Q,WU X,NIU X,et al.Integrated metagenomic and metabolomic analyses of the effects of total flavonoids of Rhizoma Drynariae on reducing ovariectomized-induced osteoporosis by regulating gut microbiota and related metabolites[J].PLoS One,2025,20(2):e0317832.
[39] XIONG H H,LIN S Y,CHEN L L,et al.The interaction between flavonoids and intestinal microbes:a review[J].Foods(Basel,Switzerland),2023,12(2):320.
[40] LI J,HAOMING YOU,HU Y,et al.Effects of traditional Chinese medicine Zuo-Gui-Wan on gut microbiota in an osteoporotic mouse model[J].J Orthop Surg Res,2025,20(1):128.
[41] ZHAN W,DENG M,HUANG X,et al.Pueraria lobata-derived exosome-like nanovesicles alleviate osteoporosis by enhancing autophagy[J].J Control Release,2023,364:644-653.
[42] XUE H,LIANG B,WANG Y,et al.The regulatory effect of polysaccharides on the gut microbiota and their effect on human health:a review[J].Int J Biol Macromol,2024,270(Pt 2):132170.
[43] 韩京辰,廖建晖,吴官保,等.补肾活血汤对去势骨质疏松大鼠TLR4/MyD88/NF-κB信号通路及肠道菌群的影响[J].时珍国医国药,2024,35(5):1127-1131.
[44] LI W,LI T,TANG Z,et al.Taohong Siwu decoction promotes the process of fracture healing by activating the VEGF-FAK signal pathway and systemically regulating the gut micro-biota[J].J Appl Microbiol,2022,133(3):1363-1377.
[45] LI B,LIU M,WANG Y,et al.Puerarin improves the bone micro-environment to inhibit OVX-induced osteoporosis via modulating SCFAs released by the gut microbiota and re-pairing intestinal mucosal integrity[J].Biomed Pharmacother,2020,132:110923.
[46] 马靖,王凤云,张佳琪,等.基于细胞信号通路探讨葛根芩连汤治疗溃疡性结肠炎的研究进展[J].中国实验方剂学杂志,2021,27(17):186-192.

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备注/Memo

备注/Memo:
基金项目:深圳市引进中医药高层次医学团队立项项目(SZZYSM202311020); 深圳市坪山区卫生健康系统科研项目(2024135,2022110)
通信作者:龚春柱 E-mail:gczq_82@126.com
(收稿日期:2025-11-16 本文编辑:杨雅)
更新日期/Last Update: 2026-07-20