胰岛素样生长因子-Ⅰ促骨质疏松骨折愈合的实验研究

目的本实验通过对胰岛素样生长因子-1在骨质疏松大鼠骨折端的局部应用,经过对骨折愈合部位的动态观察,得出科学结论,为进一步临床应用提供理论基础和使用依据。方法选择96只成年雌性SD大鼠,按随机数字表分成6组:正常对照组(N)、骨质疏松对照组(O)和4个实验组(A,B,C,D),除正常对照组造成骨质疏松模型,将其余大鼠造成左胫骨骨折模型,并于术后第1天起,连续2d于骨折处注射不同的注射液。正常对照组(N)、骨质疏松对照组(O)注射三蒸水;4个实验组注射胰岛素样生长因子-1(A组1ng/kg,B组10ng/kg,C组100ng/kg,D组1000ng/kg)。于手术后12、21、30、40d从每组抽取样本作动态X线片检查,左胫骨骨折处三点应力实验及组织学观察。将所得数据进行统计学分析。结果①正常对照组(N)、骨质疏松对照组(O)的愈合过程符合正常骨折与骨质疏松骨折愈合的变化规律。4个实验组愈合时程缩短。②影像学:术后12d,C组、D组有少量骨痂形成。术后21d,各组均有骨痂形成,C组、D组骨折线变模糊。术后30d,C组、D组多量骨痂形成,局部有增粗。术后40d,C组、D组骨折处大量骨痂形成,局部增粗,骨密度增高,其余各组骨折线均已变模糊。③生物力学:各组内,随着术后时间的延长,抗压强度逐步增强并出现峰值,D组出现早而明确。④组织学:骨折后一定时间内,各组的软骨细胞数目逐渐增多。D组数目增长最快,C组数目增长其次,O组数目增长最慢。C组、D组较其余组愈合过程提前,其中D组愈合质量较C组佳,与影像学变化相符合。结论①胰岛素样生长因子体内局部注射可以促进骨质疏松骨折的骨折愈合。②胰岛素样生长因子促进愈合的程度与胰岛素样生长因子的注射剂量存在剂量依赖关系。

An experimental study of insulin-like growth factors-Ⅰ in the process of osteoporotic fracture union

Objective To serially observe the union of ostoporotic fracture in rats treated with local insulin-like growth factor-I(IGF-I),which forms a rationale for subsequent clinical application.Methods 96 female SD rats were randomized into the normal control group(group N),osteoporosis group(group O) and four experimental groups(groups A,B,C and D).The rats except for those in the normal control group were removed of bilateral ovaries resulting in osteoporosis after 12 weeks.Model of left tibial fracture was established in all the rats.Starting from day 1,the sites of fracture were given different injections for two consecutive days:triple distilled water for groups N and O,and IGF-I for four experimental groups(A 1 ng/kg,B 10 ng/kg,C 100 ng/kg,D 1000 ng/kg).On days 12,21,30 and 40,each group was sampled for evaluation using radiography,three-point stress test and histology.All the data were analyzed statistically.Results(1) The healing process in the groups N and O was consistent with as found for bone union in normal and osteoporotic fractures;(2) Imaging findings showed minimal callus formation in groups C and D on day 12,obvious callus formation in all groups and blurring of the fracture line in groups C and D on day 21,considerable callus formation with local thickening in groups C and D on day 30,massive callus formation with local thickening and increased bone mass density in groups C and D,as well as blurring of fracture lines in all groups on day 40.(3) Biomechanics showed an increase in bone anti-stress intensity towards a peak in all the groups over time.The peak was firstly recognized in the group D.(4) By histology,the number of chondrocytes in each group increased gradually over a period after bone fracture.The rate of increase was the quickest in group D,followed by group C,and was the slowest in group O.Groups C and D experienced earlier healing of the bone fracture than the others,with better outcomes in group D vs group C.All these processes corresponded with what were seen in imaging.Conclusion(1) Local injection of IGF-I may promote the union of osteoporotic fracture;(2) IGF-I promoted the union in a dose-dependent pattern.