【摘要】：研究目的:通過局部應(yīng)用VEGFR抑制劑PTK787,探討PTK787對骨缺損修復(fù)過程中血管再生相關(guān)因子的調(diào)節(jié)作用;同時(shí)探討血管再生的變化是否影響神經(jīng)再生。研究方法:取成年雄性大鼠32只隨機(jī)分成4組。在頂骨兩側(cè)對稱性的制備直徑為5mm的標(biāo)準(zhǔn)骨缺損模型,實(shí)驗(yàn)組骨缺損區(qū)通過微型滲透泵以1ul/h的速度持續(xù)7天灌注PTK78713.125mg。對照組灌注液不含有PTK787的溶液。各組老鼠分別于術(shù)后3天、7天、14天、28天處死取材。通過對CD34、VEGF和VEGFR2進(jìn)行免疫組化染色以及微血管計(jì)數(shù)評價(jià)PTK787對血管再生的影響。同時(shí)對不同時(shí)間點(diǎn)骨缺損區(qū)神經(jīng)元標(biāo)記物βIII-tubulin進(jìn)行免疫組織化學(xué)染色,探討PTK787調(diào)節(jié)血管再生過程中對神經(jīng)再生的影響。研究結(jié)果:結(jié)果表明骨缺損修復(fù)過程中各個(gè)時(shí)間點(diǎn)對照組CD34的表達(dá)均高于PTK787導(dǎo)入的實(shí)驗(yàn)組,7天組及14天組實(shí)驗(yàn)組與對照組CD34的陽性表達(dá)差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。雖然實(shí)驗(yàn)組與對照組血管數(shù)目的差異沒有統(tǒng)計(jì)學(xué)意義,但可以觀察到對照組血管數(shù)目均高于實(shí)驗(yàn)組。VEGF的表達(dá)在7天、14天、28天組對照組高于實(shí)驗(yàn)組,且7天、28天實(shí)驗(yàn)組與對照組的差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。VEGFR2的表達(dá)在3天,14天,28天對照組高于實(shí)驗(yàn)組,且差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。β-IIItublin在3天、7天、14天、28天實(shí)驗(yàn)組的表達(dá)較對照組低,其中3天實(shí)驗(yàn)組與對照組的差別具有統(tǒng)計(jì)學(xué)意義。結(jié)論:VEGFR抑制劑PTK787抑制骨修復(fù)過程中的血管再生,其可能是由于VEGF/VEGFR-2的表達(dá)降低而引起的。同時(shí)血管再生的抑制也對神經(jīng)再生產(chǎn)生一定的抑制作用。
[Abstract]:Objective: to investigate the effects of VEGFR inhibitor PTK787 on the regulation of vascular regeneration related factors during bone defect repair and whether the changes of vascular regeneration affect nerve regeneration. Methods: 32 adult male rats were randomly divided into 4 groups. The standard bone defect model with the diameter of 5mm was prepared in the parietal bone symmetrically. In the experimental group, PTK 78713.125 mg / g was perfused to the bone defect area through a mini osmotic pump at the speed of 1ul/h for 7 days. The control group did not contain PTK787 solution. The rats in each group were killed 3 days, 7 days, 14 days and 28 days after operation. The effects of PTK787 on vascular regeneration were evaluated by immunohistochemical staining and microvessel count. At the same time, immunohistochemical staining of 尾 III-tubulin, a neuron marker in bone defect area at different time points, was carried out to investigate the effect of PTK787 on nerve regeneration in the process of vascular regeneration. Results: the results showed that the expression of CD34 in the control group was significantly higher than that in the experimental group on day 7 and day 14 during the bone defect repair (P0.05). Although there was no significant difference in the number of blood vessels between the experimental group and the control group, it was observed that the number of blood vessels in the control group was higher than that in the experimental group, and the expression of VEGF in the control group was higher than that in the control group on the 7th day and 14th day after 28 days. The expression of VEGFR2 in the experimental group was significantly higher than that in the control group on the 3rd day, the 14th day and the 28th day, and the difference was statistically significant (P0.05). The expression of 尾 -IIItublin in the experimental group was lower than that in the control group on the 3rd day, the 7th day, the 14th day, and the 28 day, the expression of VEGFR2 in the experimental group was lower than that in the control group. The difference between the experimental group and the control group was statistically significant on 3 days. Conclusion PTK787 inhibits vascular regeneration during bone repair, which may be due to the decrease of VEGF/VEGFR-2 expression. At the same time, the inhibition of vascular regeneration also has a certain inhibitory effect on nerve regeneration.
【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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