Treatment with α-lipoic acid enhances the bone healing after femoral fracture model of rats

Treatment with α-lipoic acid enhances the bone healing after femoral fracture model of rats
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DOI:
10.1007/s00210-014-1021-1
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发表时间:
2014-11-01
影响因子:
3.6
通讯作者:
Kovaci, Halim
Kovaci, Halim
中科院分区:
医学4区
文献类型:
--
作者:
Aydin, Ali;Halici, Zekai;Kovaci, Halim

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本研究调查了α-硫辛酸(α-LA)的骨折愈合效果,在骨折诱导后1个月内,每天口服一次预防性治疗模式。将大鼠随机分为假手术组(1组)、股骨骨折对照组(2组)、股骨骨折+ 25 mg/kg α-LA组(3组)和股骨骨折+ 50 mg/kg α-LA组(4组)。从术后第1天开始,实验组大鼠每天一次口服25或50 mg/kg α-LA,持续30天。术后30天,对大鼠进行X射线成像,然后安乐死以采集血液和组织。对样品进行组织学、生物化学、分子、计算机断层扫描(CT)和机械强度试验。血清骨钙素(OC)、骨桥蛋白(OP)、肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)水平在第2组和第3组之间无显著差异。第4组血清OC、OP、TNF-α和IL-6水平显著低于第3组。根据X线图像,骨折愈合的分期在第2组中评分为< 2,在第3组中评分为> 2,在第4组中评分为> 3。在第2组中,平均评分小于2表明骨折愈合不充分;两个α-LA组的平均评分均> 2,表明愈合进展。假手术组的转化生长因子β(TGF-β)信使RNA(mRNA)水平显著高于股骨骨折对照组。与骨折组相比,两种剂量的α-LA均增加TGF-β mRNA表达。骨折后4周的CT结果和生物力学测试表明,α-LA加速了骨愈合,这通过体视学分析得到证实,其中50 mg/kg α-LA增加了破骨细胞的数量。我们的研究结果表明,α-LA补充剂促进大鼠股骨骨折的愈合。
This study investigated the fracture-healing effects of alpha-lipoic acid (alpha-LA), which was applied orally once daily in preventive treatment mode during 1 month after fracture induction. Rats were randomly divided into sham-operated group (group 1), femoral fracture control (group 2), femoral fracture + 25 mg/kg alpha-LA (group 3), and femoral fracture + 50 mg/kg alpha-LA (group 4). Rats in the experimental groups were orally administered 25 or 50 mg/kg alpha-LA once daily for 30 days starting from postoperative day 1. Thirty days postoperatively, the rats underwent X-ray imaging and were then euthanized for blood and tissue collection. Histopathological, biochemical, molecular, computed tomography (CT), and mechanical strength tests were performed on samples. The serum levels of osteocalcin (OC), osteopontin (OP), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) did not differ significantly between groups 2 and 3. Serum OC, OP, TNF-alpha, and IL-6 levels in group 4 were significantly lower than those in group 3. From X-ray images, staging for fracture healing was scored as < 2 in group 2, > 2 in group 3, and > 3 in group 4. In group 2, the average score of less than 2 suggests insufficient fracture healing; those of both the alpha-LA groups were > 2, indicating progression of healing. Transforming growth factor beta (TGF-beta) messenger RNA (mRNA) levels were significantly higher in the sham group than in the femoral fracture control. Both doses of alpha-LA increased TGF-beta mRNA expression compared to the fracture group. CT results and biomechanical testing at 4 week after fracture demonstrated that alpha-LA has fastened bone healing, which was confirmed by stereological analyses in which 50 mg/kg alpha-LA increased the number of osteoclasts. Our findings indicate that alpha-LA supplementation promotes healing of femoral fractures in rats.