成纤维细胞生长因子受体3（FGFR3）在失神经骨折愈合过程中对骨痂矿化的机制研究

发布时间：2018-04-04 15:07

本文选题：成纤维细胞生长因子受体　切入点：失神经　出处：《兰州大学》2017年硕士论文

【摘要】：目的成纤维细胞生长因子受体3是是酪氨酸家族里面位于细胞膜表面的一种膜蛋白,在参于组织修复、信号传导、细胞再生分化、凋亡中发挥着重要作用。大量国内外研究发现,成纤维细胞生长因子受体3是成纤维细胞生长因子家族里唯一一个负向调控骨骼代谢。在临床中某些遗传病如软骨发育不全(ACH)、季肋发育不全(HCH)和致死性骨发育不全(TD)等都与FGFR3基因突变有关。而在失神经骨折愈合中,FGFR3的报道甚少。并且在大鼠失神经骨折愈合过程中产生的骨痂是病理性骨痂,强度差,密度分布不均匀,本实验研究FGFR3与失神经骨痂的关系。通过建立失神经骨折模型并给予注射FGFR3抑制剂,观察骨痂生成过程中钙盐沉积速率。探讨该受体与失神经骨折愈合过程中骨痂矿化的关系以及骨吸收和骨折愈合之间的关系。为如何改善脊髓损伤后骨质的流失及骨痂的矿化提供一个理论依据。方法本研究将96只成年健康雌性wistar大鼠随机分为实验组和对照组。实验组建立T10脊髓离断下的胫骨骨折模型,并于术后给予FGFR3阻滞剂;对照组为T10脊髓离断合并胫骨骨折模型,术后给予等剂量生理盐水,分别于术后第7、14、21、28天取标本(每个时间点=10只),经固定、脱钙处理后,在骨折端上下5 mm处修剪标本,石蜡包埋,切成6μm切片。切片应用于臧红固绿染色、masson三色染色。并分别于术后7、14、21、28天拍X片、骨痂骨密度测定,另每组另外8只大鼠用于钙黄绿素双标实验,并做硬组织切片,行VG染色。结果失神经后实验组骨痂骨密度较对照组相比,骨痂骨密度明显增高,具有统计学差异(p0.05)。双荧光标记宽度实验组较对照组明显增宽(p0.05)。影像学显示实验组骨折愈合速度明显高于对照组,并且在组织学方面提示不同时间点实验组在骨折愈合进程加速。结论FGFR3参与大鼠失神经后骨折愈合过程中骨痂的矿化过程,负性调节骨痂的矿化,在骨折愈合塑性重建中发挥重要作用。
[Abstract]:A large number of domestic and foreign studies have found that fibroblast growth factor receptor 3 is the only negative regulation of bone metabolism in the fibroblast growth factor family.In clinic, some hereditary diseases, such as chondroplasia, FGFR3) and fatal bone dysplasia, are associated with FGFR3 gene mutation.FGFR 3 was rarely reported in the healing of denervated fractures.The callus produced during the healing of denervated fracture in rats was pathological callus with poor strength and uneven density distribution. This study was conducted to study the relationship between FGFR3 and denervated callus.The calcium deposition rate during callus formation was observed by establishing denervated fracture model and injecting FGFR3 inhibitor.To investigate the relationship between the receptor and callus mineralization in the healing of denervated fractures and the relationship between bone resorption and fracture healing.To provide a theoretical basis for improving bone loss and callus mineralization after spinal cord injury.Methods 96 adult female wistar rats were randomly divided into experimental group and control group.The experimental group established tibial fracture model with T10 spinal cord fracture and was treated with FGFR3 blocker after operation, while the control group was treated with normal saline at the same dose after operation, while the control group was treated with T10 spinal cord fracture with tibial fracture.The sections were applied to Zang Hong solid green staining and mass on three color staining.The bone mineral density of callus was measured at 28 days after operation. The other 8 rats in each group were used for calcitonin double labeling test, hard tissue sections and VG staining.Results the bone mineral density of callus in the experimental group after denervation was significantly higher than that in the control group (P 0.05).The width of double fluorescence labeling in the experimental group was significantly wider than that in the control group.Imaging showed that the fracture healing speed in the experimental group was significantly higher than that in the control group, and histologically, the healing process of the experimental group was accelerated at different time points.Conclusion FGFR3 is involved in the mineralization of callus in the healing process of denervated fracture in rats, and plays an important role in plastic reconstruction of fracture healing.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.2;R683

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