二甲双胍对小鼠激素性股骨头坏死影响的实验研究  

Experimental research on the effects of metformin on steroid-induced osteonecrosis of mice femoral head

作　　者：姜锋[1] 王晓[1] 李国军[1] 朱书涛[1] 郭阿雷 孟涛[2] 宋仕永[3] 

机构地区：[1]河南大学附属淮河医院骨科,开封市475000 [2]河南大学医学院,开封市475000 [3]河南大学药学院,开封市475000

出　　处：《实用医学杂志》2014年第20期3210-3213,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:51375142)

摘　　要：目的:探讨二甲双胍对小鼠激素性股骨头坏死的防治效应。方法:昆明小鼠36只,随机分为3组(n=12):空白对照组A,模型组B,二甲双胍组C,B、C组按10mL/kg腹腔注射马血清,间隔2周后按5mL/kg再次腹腔注射马血清,第2次注射马血清同时肌肉注射醋酸泼尼松龙45mL/(kg·d),共5d,制备股骨头坏死模型。应用激素同时B组灌服生理盐水10mL/(kg·d),C组按0.2g/(kg·d)的剂量餐后灌服二甲双胍。A组不制备模型,于同时间点肌肉注射和灌服等量生理盐水。各组于造模前、造模后2、4、6周行血清总胆固醇(TC)、甘油三酯(TG)、血管性血友病因子(VWF)、纤溶酶原激活物抑制剂-1(PAI-1)含量检测,于造模后2、4、6周各组随机取4只小鼠处死,组织形态学观察股骨头情况。结果:3组各时间点股骨头外观、形态及关节软骨面均正常。B组较C组空骨陷窝率明显增高(P<0.05),A、C组间无明显差异(P>0.05)。TC、TG测定结果显示C组2、4、6周显著低于B组(P<0.05),但高于A组(P<0.05)。VWF、PAI-1测定结果显示C组2、4周明显低于B组(P<0.05),6周差异无统计学意义(P>0.05),A、C组间比较差异均无统计学意义。结论:二甲双胍可减轻激素所致的高脂、高凝、低纤状态,从而有效预防小鼠激素性股骨头缺血坏死。Objective To explore the effect of prevention and treatment on steroid-induced osteonecrosis of mice femoral head（ONFH） treated with mefformin. Methods Thirty-six Kunming mice were randomly divided into three groups （n = 12） ： A （ Control Group）, B （ Model Group） and C （Prevention Group）. For producing ONFH mice models, did the intraperitoneal injection of horse serum （ 10 mL/kg） to B and C firstly. After two weeks, continuing the intraperitoneal injection of horse serum （5 mL/kg） again with the prednisolone intramuscularly [45 mL/（kg. day）, totally for 5 days]. Meanwhile, feeding normal saline 10 mL/（kg-day） to B and feeding mefformin hydrochloride [ 0.2 g/（kg-day） ] to C. For A, mice were only given normal saline intramuscularly and intragastrically in equal quantity at the same time. The contents of serum cholesterol （TC）, triglycerid （TG）, plasma von willebrand factor （VWF） and plasminogen activator inhibitor 1 （PAI-1 ） were determined at the 2nd, 4th and 6th week after treatment. The micewere sacrificed at 2nd, 4th, and 6th weekafter treatment, and femoral heads were harvested to do histopathology analysis. Results The appearance and shape of the femoral head and the surface of cartilages were normal. The percentage of empty osteocyte lacunae in B was significantly higher than that in C （P 〈 0.05）, there was no significant difference between A and C （P 〉 0.05）. TC and TG contents in C were significantly lower than that in B in 2th,4th,6th weeek（P 〈 0.05）, and higher than that in A（P 〈 0.05）. VWF and PAI-1 level in C were significantly lower than that in B at 2nd and 4th week （P 〈 0.05）, but there were no statistical significance at 6th week. there were no statistical significance for the comparison between A and C. Conclusion Mefformin can prevent steroid-induced ONFH by improving hyperlipemia, hypercoagulability and hypofibrinolysis, then effectively prevent osteonecrosis.

关 键 词：激素性股骨头坏死 二甲双胍 小鼠 

分 类 号：R681.8[医药卫生—骨科学]