本文關(guān)鍵詞：VEGFR抑制劑PTK787對新骨形成及骨改建的可能調(diào)節(jié)作用　出處：《福建醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： VEGF PTK787 骨缺損 骨形成 骨改建

【摘要】：研究目的:體內(nèi)骨組織的改建、再生過程,是骨形成和骨吸收相互協(xié)調(diào)作用的過程,是由成骨細(xì)胞和破骨細(xì)胞之間相互協(xié)調(diào)完成的。血管生成是骨改建和骨再生的關(guān)鍵因素。關(guān)鍵的血管生成因子VEGF參與血管生成和骨生成。PTK787是一種強有力的VEGFR抑制劑,對VEGFR有高度特異性,阻斷VEGF/VEGFR信號傳導(dǎo)途徑。本研究通過利用微滲透泵將VEGFR抑制劑PTK787早期持續(xù)恒速灌注到大鼠顱頂骨標(biāo)準(zhǔn)骨缺損模型中,探討PTK787通過抑制VEGFR對骨缺損區(qū)新骨形成和骨改建的影響及可能的調(diào)節(jié)作用機制。研究方法:32只雄性成年SD大鼠隨機分成4組。在顱頂骨雙側(cè)上建立對稱的直徑5毫米的標(biāo)準(zhǔn)骨缺損模型,右側(cè)骨缺損區(qū)(實驗側(cè))通過微滲透泵以1μl/h的泵速持續(xù)7天灌注13.125mg的PTK787,左側(cè)骨缺損區(qū)(對照側(cè))灌注不含PTK787的溶劑(5%DMSO+1%Tween80+94%蒸餾水)。各組大鼠分別于術(shù)后3天、7天、14天及28天予以處死。分別通過免疫組化染色技術(shù)和特殊染色技術(shù)(TRAP染色)檢測骨缺損區(qū)與成骨活性相關(guān)的BMP-2、TGF-β1的表達(dá)情況及積分光密度值(IOD)、與破骨活性相關(guān)的RANKL和TRAP的表達(dá)情況及IOD值,并進行半定量統(tǒng)計分析。研究結(jié)果:對各指標(biāo)的積分光密度值進行統(tǒng)計分析結(jié)果表明在術(shù)后3天和7天BMP-2、TGF-β1及RANKL的陽性表達(dá)量對照組均明顯高于實驗組,且兩組間的差異具有統(tǒng)計學(xué)意義。在術(shù)后14天時,TGF-β1的陽性表達(dá)量及破骨細(xì)胞活性對照組均明顯高于實驗組,并且兩組間的差異具有統(tǒng)計學(xué)意義。在術(shù)后28天時,對照組的破骨細(xì)胞活性明顯高于實驗組,且兩組間的差異具有統(tǒng)計學(xué)意義。在術(shù)后14天及28天時,實驗組的RANKL積分光密度值均高于對照組,但兩組間差異不具有統(tǒng)計學(xué)意義。余時間點差異無統(tǒng)計學(xué)意義。結(jié)論:研究結(jié)果表明骨缺損區(qū)導(dǎo)入VEGFR抑制劑PTK787能參與調(diào)節(jié)骨生長因子活性和破骨細(xì)胞活性。結(jié)果證實了PTK787可通過調(diào)節(jié)成骨細(xì)胞活性與破骨細(xì)胞活性,進而影響骨缺損修復(fù)過程中的新骨形成以及骨改建過程。
[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.

【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R78

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本文編號：1370200