中草药通过肠道菌群对动物骨代谢的影响

doi:10.11843/j.issn.0366-6964.2023.10.006

摘要/Abstract

摘要： 骨代谢是在各种骨细胞参与下对骨骼进行不断修复和重塑的动态过程。骨代谢的平衡对于维持骨密度以及骨强度等具有重要意义。肠道菌群被认为是机体内的第二大基因库，在维持动物健康中发挥重要作用。近年来，骨代谢与肠道菌群之间的联系逐渐成为研究热点。肠道菌群是一个复杂的微生态系统，可以通过调节机体代谢、免疫系统以及内分泌等多种方式维持动物的骨骼健康。中草药内丰富的活性成分可以调节肠道菌群的结构和组成，进而可维持菌群的相对平衡，且研究发现中草药、肠道菌群以及骨代谢三者之间存在紧密的联系。综合国内外对骨代谢、肠道菌群与中药之间的各项研究，本文从中草药对肠道菌群的影响、肠道菌群对骨代谢的影响以及中草药通过肠道菌群对骨代谢的影响进行综述，为后续中草药基于肠-骨轴改善骨代谢的研究提供参考依据。

关键词: 中草药, 肠道菌群, 骨代谢, 骨骼生长

Abstract: Bone metabolism is a dynamic process of continuous remodeling and reconstruction of bones with the participation of various bone cells. The balance of bone metabolism is of great significance for maintaining bone density and bone strength. Gut microbiota is considered the second largest gene pool and plays an important role in maintaining animal health. In recent years, the relationship between bone metabolism and gut microbiota has gradually become a research hotspot. Gut microbiota is a complex microecosystem, which can maintain bone health by regulating metabolism, immune system and endocrine in animals. The abundant active ingredients in Chinese herbal medicine can regulate the structure and composition of gut microbiota, and thus maintain the relative balance of microorganism. It has been found that there is a close relationship among Chinese herbal medicine, gut microbiota and bone metabolism. Based on the worldwild research on bone metabolism, gut microbiota and traditional Chinese medicine, this paper summarizes the influence of Chinese herbal medicine on gut microbes, gut microbiota on bone metabolism, along with the effects of Chinese herbal medicine on bone metabolism through gut microbiota, which will provide a reference for the subsequent research on improving bone metabolism based on gut-bone axis.

Key words: Chinese herbal medicine, gut microbiota, bone metabolism, bone growth

中图分类号:

S853.7

丁文丽, 米俊宪, 张朝栋, 徐博文, 黄淑成. 中草药通过肠道菌群对动物骨代谢的影响[J]. 畜牧兽医学报, 2023, 54(10): 4061-4072.

DING Wenli, MI Junxian, ZHANG Chaodong, XU Bowen, HUANG Shucheng. Effects of Chinese Herbal Medicine on Bone Metabolism through Gut Microbiota[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(10): 4061-4072.

参考文献 71

[1]	何彦锋, 徐婷婷, 陈盼, 等.肠道菌群对骨代谢影响的研究进展[J].畜牧与饲料科学, 2022, 43(4):33-38.HE Y F, XU T T, CHEN P, et al.Research progress of the effects of gut flora on bone metabolism[J].Animal Husbandry and Feed Science, 2022, 43(4):33-38.(in Chinese)
[2]	段小花, 徐志强, 葛长荣, 等.中草药复方防治肉鸡骨病的研究[J].中国畜牧兽医, 2021, 48(1):385-394.DUAN X H, XU Z Q, GE C R, et al.Prevention and treatment of a Chinese herbal medicine compound for bone disease in chickens[J].China Animal Husbandry & Veterinary Medicine, 2021, 48(1):385-394.(in Chinese)
[3]	魏伟, 陈玲, 周永进, 等.肠道菌群介导的骨代谢失衡及中药干预研究进展[J].南京中医药大学学报, 2021, 37(3):465-472.WEI W, CHEN L, ZHOU Y J, et al.Progress on gut microbiota-regulated bone metabolism imbalance and implications for Chinese medicine intervention[J].Journal of Nanjing University of Traditional Chinese Medicine, 2021, 37(3):465-472.(in Chinese)
[4]	NAKASHIMA T.Frontiers in live bone imaging researches.Amazing function of osteocyte[J].Clin Calcium, 2015, 25(6):899-905.
[5]	WANG W B, SARAZIN B A, KORNILOWICZ G, et al.Mechanically-loaded breast cancer cells modify osteocyte mechanosensitivity by secreting factors that increase osteocyte dendrite formation and downstream resorption[J].Front Endocrinol (Lausanne), 2018, 9:352.
[6]	KLEIN-NULEND J, BAKKER A D, BACABAC R G, et al.Mechanosensation and transduction in osteocytes[J].Bone, 2013, 54(2):182-190.
[7]	RHEE Y, LEE E Y, LEZCANO V, et al.Resorption controls bone anabolism driven by parathyroid hormone (PTH) receptor signaling in osteocytes[J].J Biol Chem, 2013, 288(41):29809-29820.
[8]	陈晨, 张刚, 谷铭勇, 等.骨细胞网络结构对骨形成和骨吸收的影响[J].中国骨质疏松杂志, 2016, 22(1):120-124.CHEN C, ZHANG G, GU M Y, et al.Effect of the osteocyte network on the regulation of bone formation and bone resorption[J].Chinese Journal of Osteoporosis, 2016, 22(1):120-124.(in Chinese)
[9]	豆腾飞, 汪善荣, 刘丽仙, 等.大围山微型鸡骨代谢生化指标与骨密度研究[J].畜牧与兽医, 2016, 48(11):67-70.DOU T F, WANG S R, LIU L X, et al.Biochemical parameters and bone mineral density in Daweishan miniature chicken bone[J].Animal Husbandry & Veterinary Medicine, 2016, 48(11):67-70.(in Chinese)
[10]	耿丹丹, 李潇凡, 毕瑜林, 等.畜禽微生物-肠-脑轴调节机制研究进展[J].农业生物技术学报, 2023, 31(2):404-415.GENG D D, LI X F, BI Y L, et al.Research progress on regulation mechanism of microbiota-gut-brain axis in livestock and poultry[J].Journal of Agricultural Biotechnology, 2023, 31(2):404-415.(in Chinese)
[11]	NEIJAT M, SHIRLEY R B, BARTON J, et al.Effect of dietary supplementation of Bacillus subtilis DSM29784 on hen performance, egg quality indices, and apparent retention of dietary components in laying hens from 19 to 48 weeks of age[J].Poult Sci, 2019, 98(11):5622-5635.
[12]	NARI N, GHASEMI H A.Growth performance, nutrient digestibility, bone mineralization, and hormone profile in broilers fed with phosphorus-deficient diets supplemented with butyric acid and Saccharomyces boulardii[J].Poult Sci, 2020, 99(2):926-935.
[13]	SKRYPNIK K, SULIBURSKA J.Association between the gut microbiota and mineral metabolism[J].J Sci Food Agric, 2018, 98(7):2449-2460.
[14]	陈璐璐, 刘小伟.饮食、肠道菌群与炎症性肠病[J].生物医学转化, 2021, 2(3):42-48.CHEN L L, LIU X W.Diet, gut microbiota and inflammatory bowel disease[J].Biomedical Transformation, 2021, 2(3):42-48.(in Chinese)
[15]	张安荣, 刘娇, 陈志敏, 等.丁酸梭菌对肉鸡钙磷代谢和胫骨指标的影响[J].中国畜牧兽医, 2020, 47(9):2849-2856.ZHANG A R, LIU J, CHEN Z M, et al.Effects of Clostridium butyricum on calcium and phosphorus metabolism and tibia indexes of broilers[J].China Animal Husbandry & Veterinary Medicine, 2020, 47(9):2849-2856.(in Chinese)
[16]	余洋, 曾新福, 乐敏, 等.益生菌通过肠-脑轴调控动物骨代谢的研究进展[J].中国畜牧杂志, 2021, 57(9):22-27.YU Y, ZENG X F, YUE M, et al.Research progress on probiotics regulating animal bone metabolism through gut-brain axis[J].Chinese Journal of Animal Science, 2021, 57(9):22-27.(in Chinese)
[17]	贾淑媛, 李萍.淋巴细胞亚群在类风湿关节炎患者外周血中的表达及意义[J].中国实验诊断学, 2019, 23(11):1943-1946.JIA S Y, LI P.Expression and significance of lymphocyte subsets in the peripheral blood of patients with rheumatoid arthritis[J].Chinese Journal of Laboratory Diagnosis, 2019, 23(11):1943-1946.(in Chinese)
[18]	ZAISS M M, AXMANN R, ZWERINA J, et al.Treg cells suppress osteoclast formation:a new link between the immune system and bone[J].Arthritis Rheum, 2007, 56(12):4104-4112.
[19]	WEITZMANN M N.Bone and the Immune system[J].Toxicol Pathol, 2017, 45(7):911-924.
[20]	AMDEKAR S, SINGH V, KUMAR A, et al.Lactobacillus acidophilus protected organs in experimental arthritis by regulating the pro-inflammatory cytokines[J].Indian J Clin Biochem, 2014, 29(4):471-478.
[21]	徐家宁, 陆一风, 唐昊.肠道微生物群通过SCFAs影响骨质疏松症研究进展[J/OL].海南医学院学报, 2022, doi:10.13210/j.cnki.jhmu.20220909.001.XU J N, LU Y F, TANG H.Advances in the study of gut microbiota affecting osteoporosis through SCFAs[J/OL].Journal of Hainan Medical University, 2022, doi:10.13210/j.cnki.jhmu.20220909.001.(in Chinese)
[22]	SCHWARZER M, MAKKI K, STORELLI G, et al.Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition[J].Science, 2016, 351(6275):854-857.
[23]	LUCAS S, OMATA Y, HOFMANN J, et al.Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss[J].Nat Commun, 2018, 9(1):55.
[24]	TYAGI A M, YU M C, DARBY T M, et al.The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B expression[J].Immunity, 2018, 49(6):1116-1131.e7.
[25]	KOBAYASHI Y, UEHARA S, UDAGAWA N, et al.Regulation of bone metabolism by Wnt signals[J].J Biochem, 2016, 159(4):387-392.
[26]	CHEN P, XU T T, ZHANG C D, et al.Effects of probiotics and gut microbiota on bone metabolism in chickens:a review[J].Metabolites, 2022, 12(10):1000.
[27]	SCHOENLE E, ZAPF J, HUMBEL R E, et al.Insulin-like growth factor I stimulates growth in hypophysectomized rats[J].Nature, 1982, 296(5854):252-253.
[28]	YAN J, HERZOG J W, TSANG K, et al.Gut microbiota induce IGF-1 and promote bone formation and growth[J].Proc Natl Acad Sci U S A, 2016, 113(47):E7554-E7563.
[29]	李丽娟, 林静, 王凌.肠道微生态影响绝经后骨质疏松症发生发展的研究进展[J].中国免疫学杂志, 2019, 35(16):2032-2037.LI L J, LIN J, WANG L.Advances in research on intestinal microbiota affecting development of post-menopausal osteoporosis[J].Chinese Journal of Immunology, 2019, 35(16):2032-2037.(in Chinese)
[30]	YAN J, CHARLES J F.Gut microbiota and IGF-1[J].Calcif Tissue Int, 2018, 102(4):406-414.
[31]	BAKER J, LIU J P, ROBERTSON E J, et al.Role of insulin-like growth factors in embryonic and postnatal growth[J].Cell, 1993, 75(1):73-82.
[32]	原静晨, 宋洁富, 王小健, 等.肠道菌群影响骨代谢的机制研究进展[J].国际骨科学杂志, 2021, 42(2):89-92.YUAN J C, SONG J F, WANG X J, et al.Advance in intestinal flora and bone metabolism[J].International Journal of Orthopaedics, 2021, 42(2):89-92.(in Chinese)
[33]	PARK H K, AHIMA R S.Physiology of leptin:energy homeostasis, neuroendocrine function and metabolism[J].Metabolism, 2015, 64(1):24-34.
[34]	林懋惺, 杨正兵.5-HT受体调节剂在肠易激综合征治疗中的应用进展[J].现代临床医学, 2008, 34(2):148-151.LIN M X, YANG Z B.Progress in the application of 5-HT receptor modulators in the treatment of irritable bowel syndrome[J].Journal of Modern Clinical Medicine, 2008, 34(2):148-151.(in Chinese)
[35]	DAVID S, JONATHAN M M, DAVID P O, et al.Effects of selective serotonin re-uptake inhibitors (SSRIs) antidepressants and serotonin modulators on bone metabolism in the maxillary processes:a systematic review of experimental pre-clinical studies[J].Clin Oral Implants Res, 2017, 28(S14):12.
[36]	VEMURI R, SYLVIA K E, KLEIN S L, et al.The microgenderome revealed:sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility[J].Semin Immunopathol, 2019, 41(2):265-275.
[37]	张萌萌, 张秀珍, 邓伟民, 等.骨代谢生化指标临床应用专家共识(2020)[J].中国骨质疏松杂志, 2020, 26(6):781-796.ZHANG M M, ZHANG X Z, DENG W M, et al.Expert consensus on clinical application of biochemical indicators of bone metabolism (2020)[J].Chinese Journal of Osteoporosis, 2020, 26(6):781-796.(in Chinese)
[38]	FAN Y J, CHEN S J, YU Y C, et al.A probiotic treatment containing Lactobacillus, Bifidobacterium and Enterococcus improves IBS symptoms in an open label trial[J].J Zhejiang Univ Sci B, 2006, 7(12):987-991.
[39]	周群, 曾弦, 黄丹, 等.骨碎补化学成分和生物活性研究进展[J].世界科学技术-中医药现代化, 2021, 23(8):2727-2741.ZHOU Q, ZENG X, HUANG D, et al.Research progress on the chemical composition and biological activity of Drynariae rhizoma[J].Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology, 2021, 23(8):2727-2741.(in Chinese)
[40]	郑晶晶.骨碎补总黄酮改善肉鸡胫骨软骨发育不良的试验研究[D].郑州:河南农业大学, 2022.ZHENG J J.Experimental study on of improvement tibial cartilage dysplasia by total flavonoids of rhizoma drynariae in broilers[D].Zhengzhou:Henan Agricultural University, 2022.(in Chinese)
[41]	XU T T, CHEN P, ZHANG C D, et al.Gut microbiome dysregulation drives bone damage in broiler tibial dyschondroplasia by disrupting glucose homeostasis[J].npj Biofilms Microbiomes, 2023, 9(1):1.
[42]	龙亚丽, 田启会.骨碎补总黄酮对缺氧环境中犬骨髓间充质干细胞成骨分化潜能的影响[J].畜牧兽医学报, 2022, 53(4):1280-1288.LONG Y L, TIAN Q H.Effects of total flavonoids of Drynariae rhizoma on osteogenic differentiation potential of canine bone marrow mesenchymal stem cells in hypoxic environment[J].Acta Veterinaria et Zootechnica Sinica, 2022, 53(4):1280-1288.(in Chinese)
[43]	高玉海, 葸慧荣, 杨芳芳, 等.蛇床子素对青年大鼠骨代谢的影响研究[J].解放军医药杂志, 2016, 28(10):4-7.GAO Y H, XI H R, YANG F F, et al.Effect of osthole on bone metabolism in young rats[J].Medical & Pharmaceutical Journal of Chinese People's Liberation Army, 2016, 28(10):4-7.(in Chinese)
[44]	周建, 任雪梅, 马小妮, 等.蛇床子素对体外培养大鼠股骨组织吸收的抑制作用[J].中国骨伤, 2015, 28(9):832-837.ZHOU J, REN X M, MA X N, et al.Inhibition of osthole for resorption of rats femur tissue in vitro[J].China Journal of Orthopaedics and Traumatology, 2015, 28(9):832-837.(in Chinese)
[45]	黄月, 武晓, 薄云海, 等.基于RP-UPLC-MS和HILIC-UPLC-MS的骨疏丹对糖皮质激素性骨质疏松模型大鼠干预作用的尿液代谢组学研究[J].中国药学杂志, 2016, 51(23):2045-2052.HUANG Y, WU X, BO Y H, et al.A urinary metabonomic research on the intervention effects of gushudan on prednisolone-induced oesteoprosis rats by RP-UPLC-MS and HILIC-UPLC-MS[J].Chinese Pharmaceutical Journal, 2016, 51(23):2045-2052.(in Chinese)
[46]	WAQAS M, WANG Y P, LI A Y, et al.Osthole:a coumarin derivative assuage thiram-induced tibial dyschondroplasia by regulating BMP-2 and RUNX-2 expressions in chickens[J].Antioxidants (Basel), 2019, 8(9):330.
[47]	饶鸿宇, 陈滔彬, 何彦, 等.南药巴戟天化学成分与药理研究进展[J].中南药学, 2018, 16(11):1567-1574.RAO H Y, CHEN T B, HE Y, et al.Chemical components and pharmacological effect of Morinda officinalis Radix[J].Central South Pharmacy, 2018, 16(11):1567-1574.(in Chinese)
[48]	曹芹芹, 岳珂, 林露茜, 等.福美双对肉鸡股骨生长发育的影响及巴戟天多糖保护效果的研究[J].畜牧与饲料科学, 2021, 42(4):110-117.CAO Q Q, YUE K, LIN L X, et al.Effect of thiram on femoral growth and development in broiler chickens and protective efficacy of Morinda officinalis polysaccharide[J].Animal Husbandry and Feed Science, 2021, 42(4):110-117.(in Chinese)
[49]	ZHANG C D, XU T T, LIN L X, et al.Morinda officinalis polysaccharides ameliorates bone growth by attenuating oxidative stress and regulating the gut microbiota in thiram-induced tibial dyschondroplasia chickens[J].Metabolites, 2022, 12(10):958.
[50]	李宇, 蔡萧君, 王钦, 等.巴戟天对慢性应激大鼠肠道微生物代谢多样性的影响[J].中国中医药信息杂志, 2022, 29(2):55-62.LI Y, CAI X J, WANG Q, et al.Effects of Morindae officinalis Radix on intestinal microbial metabolic diversity in chronic stress rats[J].Chinese Journal of Information on Traditional Chinese Medicine, 2022, 29(2):55-62.(in Chinese)
[51]	徐玉德, 徐玉娥, 周明旺, 等.补肾中药通过Runx2基因调控骨代谢相关研究进展[J].中国中医药信息杂志, 2021, 28(2):141-144.XU Y D, XU Y E, ZHOU M W, et al.Research progress in regulation of Runx2 gene through kidney-tonifying herbs in osteoporosis[J].Chinese Journal of Information on Traditional Chinese Medicine, 2021, 28(2):141-144.(in Chinese)
[52]	罗伟, 王亚芹, 冯晗, 等.杜仲抗骨质疏松及其机制研究进展[J].中国临床药理学与治疗学, 2016, 21(12):1434-1440.LUO W, WANG Y Q, FENG H, et al.Advance of Eucommia ulmoides Oliver. for anti-osteoporosis[J].Chinese Journal of Clinical Pharmacology and Therapeutics, 2016, 21(12):1434-1440.(in Chinese)
[53]	ZHAO X, WANG Y J, NIE Z Y, et al.Eucommia ulmoides leaf extract alters gut microbiota composition, enhances short-chain fatty acids production, and ameliorates osteoporosis in the senescence-accelerated mouse P6 (SAMP6) model[J].Food Sci Nutr, 2020, 8(9):4897-4906.
[54]	赵宝宝, 李兴勇, 董万涛, 等.中药通过调控短链脂肪酸防治骨质疏松症的研究进展[J].中国骨质疏松杂志, 2023, 29(1):104-108.ZHAO B B, LI X Y, DONG W T, et al.Research progress in the prevention and treatment of osteoporosis with Chinese medicine by regulating short-chain fatty acids[J].Chinese Journal of Osteoporosis, 2023, 29(1):104-108.(in Chinese)
[55]	蒋校文, 张翼, 范晓升, 等.杜仲醇提取物对兔下颌牵张成骨的影响[J].中国组织工程研究, 2015, 19(42):6725-6729.JIANG X W, ZHANG Y, FAN X S, et al.Effects of eucommia alcohol extract on a rabbit model of mandibular distraction osteogenesis[J].Chinese Journal of Tissue Engineering Research, 2015, 19(42):6725-6729.(in Chinese)
[56]	郭延伟, 李松, 房殿吉.杜仲水/醇提取物促进兔脂肪基质干细胞增殖及成骨分化[J].中国组织工程研究, 2012, 16(32):5959-5962.GUO Y W, LI S, FANG D J.Effects of eucommia water/alcohol extract on proliferation and osteogenic differentiation of rabbit adipose derived mesenchymal stem cells[J].Chinese Journal of Tissue Engineering Research, 2012, 16(32):5959-5962.(in Chinese)
[57]	刘柄辰, 刘海全.淫羊藿治疗骨质疏松症的实验研究进展[J].中国中医药现代远程教育, 2021, 19(4):194-197.LIU B C, LIU H Q.Experimental research progress of Chinese herbal epimedium in the treatment of osteoporosis[J].Chinese Medicine Modern Distance Education of China, 2021, 19(4):194-197.(in Chinese)
[58]	PAN S N, CHEN A L, HAN Z H, et al.1H NMR-based metabonomic study on the effects of Epimedium on glucocorticoid-induced osteoporosis[J].J Chromatogr B, 2016, 1038:118-126.
[59]	叶敏, 万军, 王李俊, 等.中药通过调节肠道菌群治疗类风湿关节炎的研究进展[J].中草药, 2022, 53(22):7279-7284.YE M, WAN J, WANG L J, et al.Research progress of traditional Chinese medicine in treating rheumatoid arthritis by regulating intestinal flora[J].Chinese Traditional and Herbal Drugs, 2022, 53(22):7279-7284.(in Chinese)
[60]	YAN J, CHARLES J F.Gut microbiome and bone:to build, destroy, or both?[J].Curr Osteoporos Rep, 2017, 15(4):376-384.
[61]	IQBAL M, ZHANG H, MEHMOOD K, et al.Icariin:a potential compound for the recovery of tibial dyschondroplasia affected chicken via up-regulating BMP-2 expression[J].Biol Proced Online, 2018, 20:15.
[62]	胡云峰, 侯加法, 邓益锋, 等.淫羊藿苷对鸡胚成骨细胞增殖和分化的影响[J].中国农学通报, 2007, 23(3):43-46.HU Y F, HOU J F, DENG Y F, et al.Effects of icariin on proliferation and differentiation of osteoblasts from chicken embryo[J].Chinese Agricultural Science Bulletin, 2007, 23(3):43-46.(in Chinese)
[63]	王志强, 孙波.中药治疗原发性骨质疏松的进展[J].中国中医骨伤科杂志, 2014, 22(1):76-78.WANG Z Q, SUN B.Progress of traditional Chinese medicine for the treatment of primary osteoporosis[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics, 2014, 22(1):76-78.(in Chinese)
[64]	LI B, LIU M Y, WANG Y, et al.Puerarin improves the bone micro-environment to inhibit OVX-induced osteoporosis via modulating SCFAs released by the gut microbiota and repairing intestinal mucosal integrity[J].Biomed Pharmacother, 2020, 132:110923.
[65]	余应梅.葛根素对饲喂氧化大豆油肉鸡生长性能和肠道屏障功能的影响[D].南昌:江西农业大学, 2021.YU Y M.Effects of puerarin on growth performance and intestinal barrier function of broilers fed with oxidized soybean oil[D].Nanchang:Jiangxi Agricultural University, 2021.(in Chinese)
[66]	张梦丹, 罗俊崇, 黎晓雯, 等.中药复方制剂对大鼠和母猪骨质疏松症的防治效果试验[J].动物医学进展, 2019, 40(6):64-68.ZHANG M D, LUO J C, LI X W, et al.Effect of prevention and treatment on osteoporosis in rats and pigs with Chinese herbal compound[J].Progress in Veterinary Medicine, 2019, 40(6):64-68.(in Chinese)
[67]	谈志龙, 邢国胜, 于顺禄, 等.中药葛根对去卵巢大鼠骨代谢生化指标的影响[J].中国骨质疏松杂志, 2003, 9(2):108-110.TAN Z L, XING G S, YU S L, et al.Effects of Pueraria lobata on bone metabolism in ovariectomized rat[J].Chinese Journal of Osteoporosis, 2003, 9(2):108-110.(in Chinese)
[68]	万朋, 高俊涛, 刘志洋.黄芪多糖药理作用研究进展[J].吉林医药学院学报, 2010, 31(6):351-355.WAN P, GAO J T, LIU Z Y.Research progress on pharmacological effects of astraglaus polysaccharide[J].Journal of Jilin Medical College, 2010, 31(6):351-355.(in Chinese)
[69]	曲伟杰, 李进军, 王生奎.一剂复方中药对家兔骨骼愈合的影响[J].中国畜牧兽医, 2011, 38(7):215-218.QU W J, LI J J, WANG S K.The effects of one Chinese herbal medicine on fracture healing of rabbits[J].China Animal Husbandry & Veterinary Medicine, 2011, 38(7):215-218.(in Chinese)
[70]	LIU J S, LIU J, LIU L, et al.Reprogrammed intestinal functions in Astragalus polysaccharide-alleviated osteoporosis:combined analysis of transcriptomics and DNA methylomics demonstrates the significance of the gut-bone axis in treating osteoporosis[J].Food Funct, 2021, 12(10):4458-4470.
[71]	LIU J S, LIU J, LIU L, et al.The gut microbiota alteration and the key bacteria in Astragalus polysaccharides (APS)-improved osteoporosis[J].Food Res Int, 2020, 138:109811.