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浙江大学学报（医学版）
浙江大学学报（医学版）  2017, Vol. 46 Issue (6): 578-584    DOI: 10.3785/j.issn.1008-9292.2017.12.02
骨组织代谢及再生专题     
白藜芦醇对生长期大鼠峰值骨量的影响
葸慧荣1(),高玉海1,杨芳芳1,李文苑1,马慧萍2,陈克明1,*()
1. 兰州军区兰州总医院全军骨科中心骨科研究所, 甘肃 兰州 730050
2. 兰州军区兰州总医院药剂科, 甘肃 兰州 730050
Effect of resveratrol on peak bone mass in growing rats
XI Huirong1(),GAO Yuhai1,YANG Fangfang1,LI Wenyuan1,MA Huiping2,CHEN Keming1,*()
1. Institute of Orthopedics, Lanzhou General Hospital of PLA, Lanzhou 730050, China
2. Department of Pharmacy, Lanzhou General Hospital of PLA, Lanzhou 730050, China
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摘要：

目的: 研究白藜芦醇对生长期大鼠峰值骨密度和骨质量的影响。方法: 36只1月龄雌性Wistar大鼠随机分为空白对照组、淫羊藿苷组和白藜芦醇组，每组12只。淫羊藿苷组灌服淫羊藿苷25 mg·kg-1·d-1，白藜芦醇组灌服白藜芦醇8.4 mg·kg-1·d-1，空白对照组灌服等体积蒸馏水。在灌胃4、8、12周时测定大鼠全身骨密度。12周时处死所有大鼠，进行股骨和椎骨离体骨密度检测、骨生物力学分析、血清骨代谢指标检测、显微CT扫描以及重要器官的器官指数计算和病理学观察。结果: 实验期间各组大鼠体质量均呈上升趋势，组间比较差异无统计学意义（P>0.05）；各组大鼠心、肝、肾、肺、子宫等的器官指数差异无统计学意义（均P>0.05），器官组织病理学也未见异常改变。灌胃12周时，淫羊藿苷组和白藜芦醇组大鼠全身骨密度均高于空白对照组（均P < 0.05），而淫羊藿苷组和白藜芦醇组之间比较差异无统计学意义（P>0.05）；右侧股骨和椎骨离体骨密度改变呈现出与全身骨密度改变相同的趋势。与空白对照组比较，淫羊藿苷组和白藜芦醇组大鼠股骨最大载荷，以及椎骨最大载荷、弹性模量显著升高（P < 0.05或P < 0.01）。与空白对照组比较，淫羊藿苷组和白藜芦醇组股骨松质骨的体积骨密度、骨小梁数目、骨小梁厚度和骨小梁占骨髓腔体积百分比（BV/TV）均显著升高（P < 0.05或P < 0.01），骨小梁分离度显著下降（P < 0.05或P < 0.01）；各组间股骨皮质骨的体积骨密度无明显变化（P>0.05）。淫羊藿苷组和白藜芦醇组骨钙素含量显著高于空白对照组（均P < 0.05），而抗酒石酸酸性磷酸酶5b（TRACP 5b）含量显著低于空白对照组（均P < 0.05）。结论: 白藜芦醇能提高骨形成、抑制骨吸收，增加青年大鼠的峰值骨密度和骨质量，增强骨强度，改善骨组织微结构，并且无明显毒副作用。
关键词： 藜芦生物碱类/药理学;  骨密度/药物作用;  骨质疏松/药物疗法;  生长期;  大鼠, Wistar    
Abstract:

Objective: To investigate the effect of resveratrol on peak bone mineral density and bone mass in growing rats. Methods: Thirty-six female healthy Wistar rats were randomly divided into control group, icariin group and resveratrol group with 12 rats in each group. Icariin (25 mg·kg-1·d-1), resveratrol (8.4 mg·kg-1·d-1) or equal volume of distilled water were given by gavage to icariin group, resveratrol group and control group, respectively. The rats were sacrificed after 12 weeks. The organ indexes were calculated and pathology sections were observed; the bone mineral density (BMD), bone biomechanics, serum bone metabolism index, and results of micro-CT scan were analyzed. Results: During the experiment, the body weight of rats showed an increasing trend and there was no significant difference among three groups (P>0.05). There were no significant differences in organ index of vital organs and pathological changes among the groups (all P>0.05). Compared with the control group, the whole body BMD, and the BMDs of femur and vertebrae in icariin and resveratrol groups were significantly increased after 12 weeks (all P<0.05). The maximum load values of femur and vertebrae, as well as elastic modulus of vertebrae in icariin and resveratrol groups were significantly higher than those in control group (P<0.05 or P<0.01). Micro-CT scan showed that the volumetric BMD, number of trabecular, trabecular thickness and bone volume/tissue volume of the cancellous bone in icariin and resveratrol groups were significantly higher and the trabecular separation was significantly lower than those in the control group (P<0.05 or P<0.01); while there was no significant difference in volumetric BMD of cortical bone for femur. The contents of osteocalcin in icariin and resveratrol groups were significantly higher than those in control group (all P<0.05), while the contents of tartarte-resistant acid phosphatase 5b (TRACP5b) were significantly lower than those in control group (all P<0.05).Conclusion: Resveratrol can inhibit bone resorption and enhance bone formation, so as to improve the peak bone mass and bone density, enhance bone strength and improve the microstructure of bone tissue in young rats.
Key words: Veratrum alkaloids/pharmacology    Bone density/drug effects    Osteoporosis/drug therapy    Trophophase    Rats, wistar
收稿日期: 2017-09-21 出版日期: 2017-12-25
CLC:  R681  
基金资助: 国家自然科学基金(81471090)
通讯作者: 陈克明     E-mail: 18709404297@163.com;chenkm@lut.cn
作者简介: 葸慧荣(1991-), 女, 硕士研究生, 主要从事抗骨质疏松症药物研究; E-mail:18709404297@163.com; https://orcid.org/0000-0001-6230-5625
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引用本文:

葸慧荣,高玉海,杨芳芳,李文苑,马慧萍,陈克明. 白藜芦醇对生长期大鼠峰值骨量的影响[J]. 浙江大学学报（医学版）, 2017, 46(6): 578-584.

XI Huirong,GAO Yuhai,YANG Fangfang,LI Wenyuan,MA Huiping,CHEN Keming. Effect of resveratrol on peak bone mass in growing rats. J Zhejiang Univ (Med Sci), 2017, 46(6): 578-584.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2017.12.02    或    http://www.zjujournals.com/med/CN/Y2017/V46/I6/578

图 1  各组大鼠体质量变化曲线
图 2  灌胃12周时各组大鼠主要器官的器官指数比较
图 3  灌胃12周时各组大鼠主要器官组织病理学检查结果(HE染色)
(g/cm2，$\bar x \pm s$，n=12)
组别 4周 8周 12周
与空白对照组比较，*P < 0.05.
空白对照组 0.134±0.007 0.144±0.006 0.148±0.006
淫羊藿苷组 0.139±0.003 0.148±0.003 0.163±0.003*
白藜芦醇组 0.135±0.009 0.149±0.010 0.162±0.007*
表 1  给药后不同时间点各组大鼠全身骨密度检测结果比较
(g/cm2，$\bar x \pm s$)
组别 n 股骨 椎骨
与空白对照组比较，*P <0.05，**P <0.01.
空白对照组 12 0.118±0.0047 0.127±0.0062
淫羊藿苷组 12 0.126±0.0010* 0.140±0.0037**
白藜芦醇组 12 0.125±0.0048* 0.141±0.0056**
表 2  给药12周时各组大鼠股骨和椎骨离体骨密度检测结果比较
($\bar x \pm s$, n=12)
组别 最大载荷(N) 弹性模量(N/mm2) 屈服强度(N)
与空白对照组比较，**P < 0.01.
空白对照组 72±13 8835±2158 122±16
淫羊藿苷组 121±15** 12 145±538 128±12
白藜芦醇组 129±14** 11 213±1231 139±14
表 3  各组股骨三点弯曲试验结果比较
($\bar x \pm s$, n=12)
组别 最大载荷(N) 弹性模量(N/mm2) 屈服强度(N)
与空白对照组比较，*P < 0.05.
空白对照组 239±55 329±27 159±59
淫羊藿苷组 292±12* 421±41* 189±38
白藜芦醇组 319±43* 419±88* 219±89
表 4  各组大鼠椎骨压缩试验结果比较
(g/cm3，$\bar x \pm s$)
组别 n 松质骨 皮质骨
与空白对照组比较，**P < 0.01.
空白对照组 6 1.64±0.13 4.88±0.07
淫羊藿苷组 6 2.44±0.08** 4.90±0.04
白藜芦醇组 6 2.38±0.06** 4.94±0.05
表 5  给药12周时显微CT检查各组大鼠股骨体积骨密度比较
图 4  给药12周时各组大鼠股骨显微CT三维重建图
($\bar x \pm s$)
组别 n 骨小梁数目(mm-1) 骨小梁厚度(μm) 骨小梁分离度(μm) BV/TV(%)
与空白对照组比较，*P < 0.05，**P < 0.01.BV/TV:骨小梁占骨髓腔体积百分比.
空白对照组 6 0.0511±0.0020 8.254±1.403 13.496±1.402 42.150±3.110
淫羊藿苷组 6 0.0628±0.0031* 11.278±1.526* 7.541±1.782* 73.562±5.231**
白藜芦醇组 6 0.0630±0.0012* 10.922±1.169* 8.078±2.267** 68.522±6.846**
表 6  各组股骨显微CT扫描松质骨量化指标比较
($\bar x \pm s$)
组别 n 骨钙素(ng/mL) TRACP 5b(U/L)
与空白对照组比较，*P < 0.05.TRACP 5b:抗酒石酸酸性磷酸酶5b.
空白对照组 6 140.02±46.33 2.87±1.40
淫羊藿苷组 6 243.42±31.89* 1.09±1.20*
白藜芦醇组 6 224.17±42.12* 1.43±0.44*
表 7  给药12周时各组大鼠血清中骨钙素和TRACP 5b含量比较
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