淫羊藿苷治疗大鼠绝经后骨质疏松症的文献研究

摘要/Abstract

摘要： 目的：评价淫羊藿苷治疗大鼠绝经后骨质疏松症的有效性及安全性，探索淫羊藿苷在绝经后骨质疏松症治疗领域的创新应用与安全使用。方法：检索国内外4个常用数据库，筛选淫羊藿苷治疗绝经后骨质疏松症大鼠的随机对照试验；采用SYRCLE动物实验偏倚风险评估工具评价所纳入文献研究，RevMan5.4.1软件进行Meta分析。结果：经过初筛与评价，纳入6项研究，共329例样本，纳入文献质量普遍偏低。Meta分析结果显示，淫羊藿苷能够显著地抑制大鼠卵巢切除后股骨(WMD=0.04，95%CI，0.01～0.08；P=0.01)与腰椎(WMD=2.47，83%CI，1.18～3.76；P=0.000 2)的骨密度下降，提高血清钙（S-Ca）、血清磷（S-P）以及骨保护素（OPG）水平，降低血液中抗酒石酸酸性磷酸酶（TRAP5b）含量；但对碱性磷酸酶（ALP）与雌二醇（E2）水平的影响仍需更多的动物实验加以探索与验证。用药安全性方面纳入文献均未报告。结论：本研究结果表明，淫羊藿苷一方面可能是通过提高卵巢切除大鼠体内S-P含量，降低TRAP5b水平而抑制骨吸收，另一方面通过提高机体内S-Ca与OPG水平而促进骨形成；进而抑制卵巢切除大鼠股骨与腰椎骨密度的下降。有关淫羊藿苷抗绝经后骨质疏松症的确切机制应进行更深入的研究，进一步探索防治绝经后骨质疏松症的安全有效措施。

关键词: font-size:13.3333px, ">淫羊藿苷；骨质疏松找症；绝经后；动物实验；文献研究

Abstract: Objective： To evaluate the efficacy of icariin in the treatment of postmenopausal osteoporosis in rats， and to explore the innovative application and safe use of icariin in the treatment of postmenopausal osteoporosis. Methods： Four databases were searched to screen randomized controlled trials of icariin in the treatment of postmenopausal osteoporosis rats； the included literatures were evaluated by the risk assessment tool for bias in animal experiments， and meta-analysis was performed by Revman 5.4.1 software. Results： After initial screening and evaluation， 6 studies were included， including 329 samples. The quality of included literature was generally low. Meta analysis showed that icariin could significantly inhibit the decrease of BMD in femur (WMD=0.04， 95% CI， 0.01-0.08； P=0.01) and lumbar spine (WMD=2.47， 83% CI， 1.18-3.76； P=0.000 2) after ovariectomy， increase the levels of S-Ca， S-P and OPG， and reduce the content of TRAP5b in blood. However， the effect on ALP and E2 levels still needs more animal experiments to explore and verify. Drug safety was not reported in the literature. Conclusion： The results suggest that icariin may inhibit bone resorption by increasing S-P content and decreasing TRAP5b level in ovariectomized rats， and promote bone formation by increasing S-Ca and OPG levels in vivo， thereby inhibiting the decrease of bone mineral density of femur and lumbar vertebrae in ovariectomized rats. The exact mechanism of icariin against postmenopausal osteoporosis should be further studied to explore the safe and effective measures for the prevention and treatment of postmenopausal osteoporosis.

Key words: font-size:13.3333px, ">Icariin； Osteoporosis； Postmenopausal； Animal experiment； Literature research

中图分类号:

耿帅, 苏琳, 曾晖, 郭宏举. 淫羊藿苷治疗大鼠绝经后骨质疏松症的文献研究[J]. 中国药物评价, 2021, 38(4): 288-293.

GENG Shuai, SU Lin, ZENG Hui, GUO Hong-ju. Literature Research of Icariin in the Treatment of Postmenopausal Osteoporosis in Rats[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2021, 38(4): 288-293.

参考文献

[1]Zhang J， Dennison E， Prieto-Alhambra D Osteoporosis epidemiology using international cohorts[J]. Curr Opin Rheumatol， 2020， 32(4)：387-393.
     [2]Shin CS， Choi HJ， Kim MJ， et al. Prevalence and risk factors of osteoporosis in Korea： a community-based cohort study with lumbar spine and hip bone mineral density[J]. Bone， 2010，47(2)：378-387.
     [3]Dempster DW. Osteoporosis and the burden of osteoporosis-related fractures [J]. Am J Manag Care， 2011， 17(suppl 6)：S164-S169.
     [4]Dima L Diab， Nelson B Watts. Postmenopausal osteoporosis[J]. Curr Opin Endocrinol Diabetes Obes， 2013， 20(6)：501-509.
     [5]Liu M， Liu D， Hong P， et al. The effect of Qigong Wuqinxi for osteopenia and primary osteoporosis： A protocol for systematic review and meta-analysis[J]. Med (Balt)， 2020， 99 (21)：e20379.
     [6]Gundala NK， Naidu VGM， Das U N. Amelioration of streptozotocin-induced type 2 diabetes mellitus in Wistar rats by arachidonic acid[J]. Biochem Biophys Res Commun， 2018， 496(1)：105-113.
     [7]Colon-Emeric C， Nordsletten L， Olson S， et al. Association between timing of zoledronic acid infusion and hip fracture healing[J]. Osteoporos Int， 2010， 12(9)：1669-1673.
     [8]Abrahamsen B， Eiken P， Eastell R. Subtrochanteric and diaphysis femur fractures in patients treated with alendronate： aregister-based national cohort study[J]. J Bone Miner Res， 2009， 24(6)：1095-1102.
     [9]Khan AA， Sándor GK， Dore E， et al. Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw[J]. J Rheumatol， 2008， 35(7)：1391-1397.
     [10]袁斯远，孔蓓蓓，盛彤，等.葛根素干预小鼠成骨细胞分化相关特征性蛋白mRNA的表达 [J]. 中国组织工程研究， 2014，42： 6732-6736.
     [11]Zhao JF， Xu JY， Xu YE， et al. High-throughput metabolomics method for discovering metabolic biomarkers and pathways to reveal effects and molecular mechanism of ethanol extract from epimedium against osteoporosis[J]. front Pharmacol，2020，11：1318.
     [12]Xi HR， Ma HP， Yang， et al. Total flavonoid extract of Epimedium herb increases the peak bone mass of young rats involving enhanced activation of the AC10/cAMP/PKA/CREB pathway[J]. J Ethnopharmacol，2018，223(15)：76-87.
     [13]Liu HG， Xiong YQ， Wang HX.Effects of water extract from epimedium on neuropeptide signaling in an ovariectomized osteoporosis rat model[J]. J Ethnopharmacol， 2018，15(221)：126-136.
     [14]Kim D， Lee J， Shim K， et al. Effects of herbal Epimedium on the improvement of bone metabolic disorder through the induction of osteogenic differentiation from bone marrow-derived mesenchymal stem cells[J]. Mol Med Rep， 2017， 15(1)：125-130.
     [15]Feifei Xu， Yan Ding， Yingying Guo. Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level approach[J]. J Ethnopharmacol， 2016，11(177)：148-160.
     [16]Yin XX， Chen ZQ， Liu ZJ， et al. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2[J]. Chin Med J，2007， 120：204-210.
     [17]Zhang G， Qin L， Hung WY， et al. Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption[J]. Bone，2006，38：818-825.
     [18]Wang Z， Wang D， Yang D， et al. The effect of icariin on bone metabolism and its potential clinical application [J]. Osteoporos Int， 2018， 29(3)：535-544.
     [19]Hooijmans C， Rovers MM， de Vries RB， et al. SYRCLE′s risk of bias tool for animal studies [J]. BMC Med Res Methodol， 2014，5(14)：43．
     [20]宋渊，李盛华，何志军，等. 淫羊藿苷对去势雌性大鼠骨质疏松的影响[J]. 军医进修学院学报， 2012， 33(4)：400-403
     [21]刘仕杰，莫新民，李劲平，等.淫羊霍苷对去卵巢骨质疏松症雌鼠的疗效及机理初步研究[J]. 中国中医基础医学杂志，2012，18 (3)：271-275.
     [22]朱彤彤，黄连弟，李俊玮，等. 淫羊藿苷对去卵巢大鼠骨质疏松症的保护作用及其机制 [J]. 吉林大学学报， 2016，42 (5)：42：915-919.
     [23]Chen GM， Wang CP， Wang JF， et al. Antiosteoporotic effect of icariin in ovariectomized rats is mediated via the Wnt/β-catenin pathway [J]. Exp Ther Med，2016，12(1)：279-287.
     [24]郭艳霞. 淫羊藿苷对去卵巢大鼠骨质疏松症的保护机制研究[J]. 四川中医， 2017，35 (7)：63-65.
     [25]Tang D， Ju CL， Liu YJ， et al. Therapeutic effect of icariin combined with stem cells on postmenopausal osteoporosis in rats[J]. J Bone Miner Metab， 2018，36(2)：180-188.
     [26]Schilling T， Ebert R， Raaijmakers N， et al. Effects of phytoestrogens and other plant-derived compounds on mesenchymal stem cells， bone maintenance and regeneration[J]. J Steroid Biochem Mol Biol，2014，139：252-261.
     [27]Peng S， Xia R， Fang H， et al. Effect of epimedium-derived phytoestrogen on bone turnover and bone microarchitecture in OVX-induced osteoporotic rats[J]. J Huazhong Univ Sci Technolog Med Sci，2008，28(2)：167-170.
     [28]肖恩，孟萍. 骨质疏松骨代谢生化指标的研究进展[J]. 中国骨质疏松杂志，2008， 14(3)：212-216.
     [29]Lacey DL， Timms E， Tan HL， et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation[J]. Cell， 1998， 93(2)：165-176.