中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (5): 657-661.doi: 10.3969/j.issn.2095-4344.1912

• 骨组织构建 bone tissue construction •    下一篇

二甲双胍改善糖尿病模型大鼠腰椎与后肢骨强度作用的差异

余佩沅1,张志达1,梁丽嫦1,杨志东2,黄锦菁1,彭建城1,梁梓扬1,何嘉辉1,招文华1,余富勇3,陈桂锋3,梁  德2,江晓兵2   

  1. 1广州中医药大学第一临床医学院,广东省广州市  510405;2广州中医药大学第一附属医院脊柱骨科,广东省广州市   510405;3广州中医药大学第二临床医学院,广东省广州市  510405
  • 收稿日期:2019-04-22 修回日期:2019-04-30 接受日期:2019-06-14 出版日期:2020-02-18 发布日期:2020-01-08
  • 通讯作者: 杨志东,教授,硕士生导师,广州中医药大学第一附属医院脊柱骨科,广东省广州市 510405 江晓兵,副教授,博士生导师,广州中医药大学第一附属医院脊柱骨科,广东省广州市 510405
  • 作者简介:余佩沅,男,1993年生,广东省惠州市人,汉族,广州中医药大学脊柱骨科在读硕士,主要从事骨质疏松症及脊柱退变性疾病研究。
  • 基金资助:
    国家自然科学基金(81674000);国家自然科学基金(81503591);国家中医临床研究基地业务建设第二批科研专项(2015L01);广东省自然科学基金(2016A030313645);广东省自然科学基金(2014A030310082);广东省科学技术厅项目(2014A020221021);广东省中医药管理局重点项目(20173006);广州市科技计划(201707010298);广州市科技计划(201710010078)

Difference in the effect of metformin on bone strength of lumbar vertebrae and hind limbs in diabetic rats

Yu Peiyuan1, Zhang Zhida1, Liang Lichang1, Yang Zhidong2, Huang Jinjing1, Peng Jiancheng1, Liang Ziyang1, He Jiahui1, Zhao Wenhua1,

Yu Fuyong3, Chen Guifeng3, Liang De2, Jiang Xiaobing2   

  1. 1the First School of Clinical Medicine of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 2Department of Spine, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 3the Second School of Clinical Medicine of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Received:2019-04-22 Revised:2019-04-30 Accepted:2019-06-14 Online:2020-02-18 Published:2020-01-08
  • Contact: Yang Zhidong, Professor, Master’s supervisor, Department of Spine, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China Jiang Xiaobing, Associate professor, Doctoral supervisor, Department of Spine, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • About author:Yu Peiyuan, Master candidate, the First School of Clinical Medicine of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81674000 and 81503591; the Second Batch of Research Project for the Construction of the National Traditional Chinese Medicine Clinical Research Base, No. 2015L01; the Natural Science Foundation of Guangdong Province, No. 2016A030313645 and 2014A030310082; the Project of Science and Technology Department of Guangdong Province, No. 2014A020221021; the Guangdong Provincial Administration of Traditional Chinese Medicine, No. 20173006; the Science and Technology Program of Guangzhou, No. 201707010298 and 201710010078

摘要:

文题释义:
骨强度:综合反映骨量和骨质量,能较全面地评价骨的生物力学特征,评价骨的抗破坏和抗变形能力。
二甲双胍:为双胍类口服降血糖药。具有多种作用机制,包括延缓葡萄糖由胃肠道的摄取,通过提高胰岛素的敏感性而增加外周葡萄糖的利用,以及抑制肝、肾过度的糖原异生。该药不降低非糖尿病患者的血糖水平。患者用药期间体质量通常减轻,血浆胆固醇、三酰甘油和前β脂蛋白水平可降低,外周葡萄糖代谢能得到改善。

背景:研究证实二甲双胍对骨代谢有一定的调节作用,但其对骨强度的作用研究在国内仍未报道。

目的:观察二甲双胍改善糖尿病大鼠腰椎、后肢骨强度的作用差异。

方法:实验方案经广州中医药大学第一附属医院动物实验伦理委员会批准。30只大鼠随机挑选6只为空白组,24只大鼠6周高糖高脂饮食后,给予链脲佐菌素(40 mg/kg)一次性腹腔注射建立 2型糖尿病大鼠模型,从中挑选造模成功12只分为模型组及二甲双胍组。二甲双胍组300 mg/(kg▪d)二甲双胍悬浊液2 mL灌胃,1次/d;空白组和模型组用0.9%氯化钠溶液2 mL灌胃,1次/d;各组均给药12周。分别于给药后8,12周检测各组大鼠腰椎、股骨及胫骨最大载荷及弹性模量,计算给药12周时二甲双胍对中轴骨及外周骨的最大载荷改善率。

结果与结论:①二甲双胍组给药8,12周后对胫骨最大载荷均升高,给药12周后对腰椎、股骨最大载荷亦升高(P < 0. 05);②给药12周后,二甲双胍组腰椎及胫骨弹性模量均高于模型组(P < 0.05);③给药12周后,二甲双胍组腰椎最大载荷改善率为38.35%,股骨最大载荷改善率为24.05%,胫骨最大载荷改善率为14.70%;④结果说明,二甲双胍对糖尿病大鼠腰椎、后肢的骨强度均有一定改善作用,且对中轴骨(腰椎)的骨强度改善作用可能优于外周骨(股骨、胫骨)。

ORCID: 0000-0002-2340-111X(余佩沅)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松组织工程

关键词: 糖尿病, 糖尿病性骨质疏松, 二甲双胍, 骨强度, 生物力学

Abstract:

BACKGROUND: Metformin has been shown to regulate bone metabolism to some extent, but its effect on bone strength is rarely reported.

OBJECTIVE: To observe the difference in the effect of metformin on the bone strength of lumbar vertebrae and hind limb in diabetic rats. 

METHODS: The study was approved by the Laboratory Animal Ethical Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. Six rats randomly selected from 30 rats were as blank group. The remaining 24 rats were given the intraperitoneal injection of streptozotocin (40 mg/kg) once after 6 weeks of high-sugar and high-fat diet to establish the model of type 2 diabetes mellitus. Twelve of them were successfully selected and divided into model group and metformin group. After modeling, in the metformin group, 300 mg/kg per day metformin suspension 2 mL was intragastrically administered once a day; the blank group and the model group were intragastrically administered 0.9% sodium chloride 2 mL once a day. Each group was administered for 12 weeks. The maximal load and elastic modulus of lumbar vertebrae, femur and tibia of each group were measured at 8 and 12 weeks after administration. The maximum load improvement rate of metformin on the central and peripheral bone at 12 weeks was calculated. 

RESULTS AND CONCLUSION: (1) The maximum load of the tibia was increased after 8 and 12 weeks of administration in the metformin group. The maximum load on the lumbar spine and femur was also increased after 12 weeks of administration (P < 0.05). (2) After 12 weeks of administration, the elastic modulus of lumbar vertebrae and tibia in the metformin group was higher than that in the model group (P < 0.05). (3) After 12 weeks of administration, the maximal load improvement rate of the lumbar spine in the metformin group was 38.35%, the maximum femur repair rate was 24.05%, and the maximum tibia load improvement rate was 14.70%. (4) These findings suggest that metformin has a certain improvement on the bone strength of the lumbar vertebrae and hind limb in diabetic rats, and the improvement of the bone strength on the central axis (lumbar spine) is better than that of the peripheral bone (femur, tibia).

Key words: diabetes, diabetic osteoporosis, metformin, bone strength, biomechanics

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