VEGFR抑制剂PTK787对新骨形成及骨改建的可能调节作用

发布时间：2018-01-02 17:22

本文关键词：VEGFR抑制剂PTK787对新骨形成及骨改建的可能调节作用　出处：《福建医科大学》2015年硕士论文　论文类型：学位论文

更多相关文章： VEGF PTK787 骨缺损 骨形成 骨改建

【摘要】：研究目的:体内骨组织的改建、再生过程,是骨形成和骨吸收相互协调作用的过程,是由成骨细胞和破骨细胞之间相互协调完成的。血管生成是骨改建和骨再生的关键因素。关键的血管生成因子VEGF参与血管生成和骨生成。PTK787是一种强有力的VEGFR抑制剂,对VEGFR有高度特异性,阻断VEGF/VEGFR信号传导途径。本研究通过利用微渗透泵将VEGFR抑制剂PTK787早期持续恒速灌注到大鼠颅顶骨标准骨缺损模型中,探讨PTK787通过抑制VEGFR对骨缺损区新骨形成和骨改建的影响及可能的调节作用机制。研究方法:32只雄性成年SD大鼠随机分成4组。在颅顶骨双侧上建立对称的直径5毫米的标准骨缺损模型,右侧骨缺损区(实验侧)通过微渗透泵以1μl/h的泵速持续7天灌注13.125mg的PTK787,左侧骨缺损区(对照侧)灌注不含PTK787的溶剂(5%DMSO+1%Tween80+94%蒸馏水)。各组大鼠分别于术后3天、7天、14天及28天予以处死。分别通过免疫组化染色技术和特殊染色技术(TRAP染色)检测骨缺损区与成骨活性相关的BMP-2、TGF-β1的表达情况及积分光密度值(IOD)、与破骨活性相关的RANKL和TRAP的表达情况及IOD值,并进行半定量统计分析。研究结果:对各指标的积分光密度值进行统计分析结果表明在术后3天和7天BMP-2、TGF-β1及RANKL的阳性表达量对照组均明显高于实验组,且两组间的差异具有统计学意义。在术后14天时,TGF-β1的阳性表达量及破骨细胞活性对照组均明显高于实验组,并且两组间的差异具有统计学意义。在术后28天时,对照组的破骨细胞活性明显高于实验组,且两组间的差异具有统计学意义。在术后14天及28天时,实验组的RANKL积分光密度值均高于对照组,但两组间差异不具有统计学意义。余时间点差异无统计学意义。结论:研究结果表明骨缺损区导入VEGFR抑制剂PTK787能参与调节骨生长因子活性和破骨细胞活性。结果证实了PTK787可通过调节成骨细胞活性与破骨细胞活性,进而影响骨缺损修复过程中的新骨形成以及骨改建过程。
[Abstract]:Objective: To study alterations in vivo bone tissue regeneration process is bone formation and bone resorption process interaction, is made between osteoblasts and osteoclasts in coordination to complete. Angiogenesis is a key factor in bone remodeling and bone regeneration. VEGF key angiogenic factor involved in angiogenesis and bone formation.PTK787 is a potent inhibitor of VEGFR, is highly specific to VEGFR, blocking the VEGF/VEGFR signal transduction pathway. In this study, through the use of micro osmotic pump to early VEGFR inhibitor PTK787 continued constant infusion into rat cranial bone defect in the standard model, to investigate the PTK787 effect by inhibiting the formation of VEGFR and bone reconstruction of bone defect the new bone and the possible regulatory mechanisms. Methods: 32 adult male SD rats were randomly divided into 4 groups. The standard bone defect model in bilateral parietal establish symmetrical 5 mm in diameter, right side The bone defect area (experimental side) by micro osmotic pump with 1 l/h pump speed for 7 days infusion of 13.125mg PTK787, on the left side of the bone defect area (control side) perfusion without PTK787 solvent (distilled water 5%DMSO+1%Tween80+94%). The rats were on the 3 postoperative day, 7 days, 14 days and 28 days to be executed. Technology and special staining techniques were stained by immunohistochemistry (TRAP staining) detection of bone defect and bone related to BMP-2 activity, TGF- beta 1 expression and integral optical density (IOD), and the expression of IOD correlated with osteoclast activity in RANKL and TRAP values, and in semi quantitative statistical analysis. Results: the integral optical density of each index value of statistical analysis showed that in the BMP-2 after 3 days and 7 days, the positive expression of TGF- beta 1 and RANKL control group were significantly higher than those in the experimental group, and there were significant differences between the two groups in the 14 day after surgery. TGF- beta 1 positive. The expression and activity of osteoclasts in control group were significantly higher than those in the experimental group, and the difference between the two groups was statistically significant. On the 28 day after surgery, osteoclast activity in control group was significantly higher than the experimental group, and there were significant differences between the two groups. After 14 days and 28 days. RANKL integral optical density value of the experimental group were higher than those in control group, but the difference between the two groups was not statistically significant. No statistically significant differences between the other time points. Conclusion: the results showed that the bone defect area into VEGFR inhibitor PTK787 can participate in the regulation of bone growth factor activity and osteoclast activity. The results show that the PTK787 can be adjusted to the activity of bone cells and osteoclast activity, thereby affecting the new bone formation during repair of bone defect and bone remodeling.

【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R78

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