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

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

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

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).