PDF(921 KB)
Improvement effect of velvet antler polypeptide in osteoporosis model rats and its effect on SIRT1/FOXO1 signaling pathway
Xueting CHI,Xiaowei HUANG,Fangyuan CHEN,Gaofeng ZHOU,Jinji WANG,Guangfu LYU,Zhe LIN,Qing GONG
PDF(921 KB)
PDF(921 KB)
Improvement effect of velvet antler polypeptide in osteoporosis model rats and its effect on SIRT1/FOXO1 signaling pathway
Objective To discuss the protective effect of velvet antler peptide (VAP) in the osteoporosis (OP) model rats,and to clarify the possible mechanism. Methods Sixty 12-week-old SD rats were randomly divided into control group, model group, positive drug group (treated with 1 mg·kg-1·d-1 of alendronate sodium by gavage), low dose of VAP group (treated with 100 mg·kg-1·d-1 VAP), medium dose of VAP group (treated with 200 mg·kg-1·d-1 VAP), and high dose of VAP group (treated with 300 mg·kg-1·d-1 VAP), and there were ten rats in each group. Except for control group,the rats in the other groups were injected with dexamethasone (2 mg·kg-1) to replicate the OP rat model, while the rats in control group were injected with the equivalent volume of saline twice a week for 11 consecutive weeks. Dual-energy X-ray absorptiometry was used to detect the bone mineral density (BMD) of femur tissue of the rats in various groups;enzyme-linked immunosorbent assay (ELISA) method was used to detect the levels of serum calcium (Ca2+), phosphate (P), osteoprotegerin (OPG), alkaline phosphatase (ALP), and osteocalcin (OCN)in serum of the rats in various groups; biochemical method was used to detect the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in serum of the rats in various groups; HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups; Western blotting method was used to detect the expression levels of silent information regulator 1 (SIRT1), catalase (CAT), Runt-related transcription factor 2 (RUNX2), and forkhead box protein O1 (FOXO1) proteins in bone tissue of the rats in various groups. Results Compared with control group, the BMD of femoral tissue of the rats in model group was decreased (P<0.05); compared with model group, the BMD of femur tissue of the rats in positive drug group, medium dose of VAP group, and high dose of VAP group were increased (P<0.05 or P<0.01). Compared with control group, the levels of Ca2+, P, OPG, and SOD activities in serum of the rats in model group were decreased (P<0.05), and the levels of ALP, OCN, and MDA were increased (P<0.05); compared with model group, the level of OPG in serum of the rats in low dose of VAP group was significantly increased(P<0.05),the levels of Ca2+, P, OPG, and activities of SOD in serum of the rats in positive drug group, medium dose of VAP group, and high dose of VAP group were significantly increased (P<0.05 or P<0.01), and the levels of ALP, OCN, and MDA in serum of the rats in positive drug group and different doses of VAP groups were decreased (P<0.05 or P<0.01). The HE staining results showed that compared with control group, the rats in model group had fewer bone cells and disordered arrangements in the bone tissue, thinner bone trabeculae with large fractures, and an expanded marrow cavity; compared with model group, the rats in positive drug group, medium dose of VAP group, and high dose of VAP group had thicker bone trabeculae arranged more tightly. The Western blotting results showed that compared with control group, the expression levels of SIRT1, CAT, RUNX2, and FOXO1 proteins in bone tissue of the rats in model group were decreased (P<0.05); compared with model group, the expression levels of SIRT1, CAT, RUNX2, and FOXO1 proteins in bone tissue of the rats in positive drug group, medium dose of VAP group, and high dose of VAP group were significantly increased (P<0.05 or P<0.01). Conclusion VAP has the protective effect against OP in the rats, and its mechanism may be related to mediating the antioxidant stress action through the SIRT1/FOXO1 signaling pathway.
Osteoporosis / Dexamethasone / Velvet antler polypeptide / Oxidative stress / Silent information regulator 1 / Forkhead box protein O1 / Signaling pathway
R285.5
| 1 | TIAN L M, YANG R F, WEI L H, et al. Prevalence of osteoporosis and related lifestyle and metabolic factors of postmenopausal women and elderly men: a cross-sectional study in Gansu Province, Northwestern of China[J]. Medicine, 2017, 96(43): e8294. |
| 2 | 严 伟, 王中汉, 刘 贺. 骨重建失衡导致骨质疏松发生的作用机制及其药物治疗策略[J]. 中国组织工程研究, 2020, 24(30): 4866-4874. |
| 3 | HUO Y S, HUO H, ZHANG J. The contribution of Deer velvet antler research to the modern biological medicine[J]. Chin J Integr Med,2014,20(10): 723-728. |
| 4 | SUI Z G, ZHANG L H, HUO Y S, et al. Bioactive components of velvet antlers and their pharmacological properties[J]. J Pharm Biomed Anal,2014,87: 229-240. |
| 5 | 龚 庆, 宋秋莹, 邱莉晶, 等. PLGA微球搭载鹿茸多肽对去卵巢骨质疏松大鼠保护作用研究[J]. 中国骨质疏松杂志, 2020, 26(6): 813-817. |
| 6 | 黄晓巍, 刘玥欣, 王晋冀, 等. 鹿茸多肽对轻度认知功能障碍大鼠学习记忆能力的改善作用及其调节Keap1/Nrf2/HO-1信号通路的机制[J]. 吉林大学学报(医学版), 2021, 47(5): 1215-1220. |
| 7 | SAPAROV A, OGAY V, NURGOZHIN T, et al. Role of the immune system in cardiac tissue damage and repair following myocardial infarction[J]. Inflamm Res, 2017, 66(9): 739-751. |
| 8 | AN Y N, ZHANG H F, WANG C, et al. Activation of ROS/MAPKs/NF-κB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis[J]. FASEB J, 2019,33(11):12515-12527. |
| 9 | LIU Y H, WANG C, WANG G, et al. Loureirin B suppresses RANKL-induced osteoclastogenesis and ovariectomized osteoporosis via attenuating NFATc1 and ROS activities[J]. Theranostics, 2019, 9(16): 4648-4662. |
| 10 | LIU G W, MA C, WANG P A, et al. Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway[J]. Biochem Biophys Res Commun, 2017, 491(2): 388-395. |
| 11 | JOHNSTON C B, DAGAR M. Osteoporosis in older adults[J]. Med Clin North Am, 2020,104(5): 873-884. |
| 12 | COTTS K G, CIFU A S.Treatment of osteoporosis[J]. JAMA, 2018, 319(10): 1040-1041. |
| 13 | 龚 伟, 郑洪新, 李 峰, 等. 鹿茸不同组分对去卵巢骨质疏松症大鼠的影响[J]. 时珍国医国药, 2019, 30(8): 1819-1821. |
| 14 | REN C, GONG W, LI F, et al. Protective and therapeutic effects of Pilose antler against kidney deficiency-induced osteoporosis[J]. Cell Mol Biol, 2019, 65(5): 24-31. |
| 15 | 付 涛, 吴晓东, 阿 力·艾拜. 水飞蓟宾通过PI3K/AKT/FoxO1通路改善骨质疏松大鼠骨代谢和骨量[J]. 中国骨质疏松杂志, 2020, 26(10): 1416-1420. |
| 16 | 王泽凤, 高 强, 朱 煜, 等. 红景天苷调控FoxO1/β-catenin通路对2型糖尿病骨质疏松大鼠的保护作用研究[J]. 中国比较医学杂志, 2021, 31(3): 55-60. |
| 17 | 时英才, 雷瑞瑞, 周栩平, 等. 岩藻多糖对氧糖剥夺诱导的新生大鼠海马脑神经元的影响[J].郑州大学学报(医学版),2023,58(6): 852-856. |
| 18 | CHEN X S, HAN D P, LIU T F, et al. Asiatic acid improves high-fat-diet-induced osteoporosis in mice via regulating SIRT1/FOXO1 signaling and inhibiting oxidative stress[J].Histol Histopathol,2022,37(8): 769-777. |
| 19 | YANG X H, JIANG T L, WANG Y, et al. The role and mechanism of SIRT1 in resveratrol-regulated osteoblast autophagy in osteoporosis rats[J]. Sci Rep, 2019, 9(1): 18424. |
| 20 | 牛建锋, 朱海慧, 杨庆宇, 等. 瑞舒伐他汀通过AMPK/Sirt1/NF-κB通路改善骨质疏松雌性大鼠骨微结构的研究[J]. 现代药物与临床, 2022, 37(1): 25-32. |
| 21 | JIANG Y X, LUO W Q, WANG B, et al. Resveratrol promotes osteogenesis via activating SIRT1/FoxO1 pathway in osteoporosis mice[J]. Life Sci, 2020, 246: 117422. |
| 22 | IYER S, HAN L, BARTELL S M, et al. Sirtuin1 (Sirt1) promotes cortical bone formation by preventing β-catenin sequestration by FoxO transcription factors in osteoblast progenitors[J]. J Biol Chem, 2014,289(35): 24069-24078. |
| 23 | 邹 毅, 冷华伟, 桂 鹏, 等. 人工虎骨粉对去卵巢大鼠骨组织中Sirt1/Runx2信号通路的影响[J]. 中国骨质疏松杂志, 2020, 26(8): 1142-1146. |
| 24 | ALMEIDA M, PORTER R M. Sirtuins and FoxOs in osteoporosis and osteoarthritis[J]. Bone, 2019, 121: 284-292. |
| 25 | LIANG W N, LI X H, LI G H, et al. Sirt1/foxo axis plays a crucial role in the mechanisms of therapeutic effects of erzhi pill in ovariectomized rats[J]. Evid Based Complement Alternat Med, 2018, 2018: 9210490. |
| 26 | KIM H N, HAN L, IYER S, et al. Sirtuin1 suppresses osteoclastogenesis by deacetylating FoxOs[J]. Mol Endocrinol, 2015, 29(10): 1498-1509. |
/
| 〈 |
|
〉 |