血管内皮细胞生长因子应用于羟基磷灰石眶内植入物的研究

Effects of endothelial growth factor on fibrovascular ingrowth into hydroxyapatite orbital implants

目的观察不同质量浓度的血管内皮生长因子(VEGF)对羟基磷灰石(HA)植入物纤维血管化的作用。方法将24只新西兰白兔随机分为A、B、C、D 4组,每组6只。各组均采用自体深筋膜覆盖HA植入物植入兔眼眶。A组为对照组,B、C、D组将HA义眼台植入前分别浸泡于质量浓度为0.5、1.5、2.5 g/L VEGF溶液中,术后分别点用上述不同质量浓度VEGF滴眼液,每日4次,连续28 d。术后14、21、28 d各组取出2个HA植入物行组织学病理学检查,比较植入物纤维血管化的情况。结果术后14 d,各组间纤维血管长度的平均值差异无统计学意义(F=34.12,P>0.05);术后21 d,各组间纤维血管长度的平均值差异有统计学意义(F=4.21,P<0.05);术后28 d,各组间纤维血管长度的平均值差异无统计学意义(F=27.67,P>0.05)。术后14 d,各组HA植入物纤维血管化程度级别差异无统计学意义(H=0.072,P>0.05);术后21 d,各组HA植入物纤维血管化程度级别差异有统计学意义(H=3.684,P<0.05);术后28 d,各组HA植入物纤维血管化程度级别差异有统计学意义(H=4.318,P<0.05)。结论质量浓度为1.5 g/L及2.5 g/L的VEGF对HA植入物术后早期的纤维血管化具有促进作用。

Objective The hydroxyapatite（HA） implanting surgery is a deal way for orbital reconstruction. Researches showed that the rejection after HA implanting surgery is associated with the delayed fibrovascularization of implants. The aim of this study was to investigate the effects of different doses of vascular endothelial growth factor （VEGF） on the fibrovascular ingrowth into hydroxyapatite orbital implants. Methods The hydroxyapatite orbital spheres embedded by quadriceps femoris fascia were implanted into 24 New Zealand white rabbits. The rabbits were divided into 4 groups randomly. The implants were treated with 0. 5,1.5 and 2.5 g/L VEGF solution prepared by normal saline solution prior to the surgery,and the eye drops with the same concentration of VEGF were topically used after surgery for 28 days respectively in 3 groups. In the control group,the untreated implants were used and normal saline solution was administered after surgery at the same way. The implants were harvested at postoperative 2, 3 and 4 weeks. The fibrovascular growth status in implants was graded based on the mean fibrovaseular length at 3： 00,6： 00,9： 00 and 12：00 position of hydroxyapati orbital spheres under the light microscopy. The use of animal followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results The fibrovascular length was gradually increased with the enhance of concentration of VEGF in various postoperative time points. The fibrovascular length in 0. 5,1.5 and 2.5 g/L VEGF groups was obvious increased in comparison with control group. No significant rising of fibrovascular proliferation was found in every group in 14 days （F = 34.12, P 〉 0.05 ） and 28 days（ F = 27.67 ,P 〉 0. 05 ） of postoperation. However, significant differences in fibrovascular proliferation were seen in 21 days （F = 4. 21 ,P 〈 0. 05 ）. There was no significant differences in mean grade of fibrovascular length in 14 days （H = 0. 072,P 〉 0. 05）. However, significant differences in fibrovascular grade were found in 21 days （ H = 3. 684, P 〈 0. 05 ） and 28 days （H =4. 318, P 〈 0. 05 ）. Conclusion The VEGF at the concentration of 1.5 and 2.5 g/L promotes the fibrovessel ingrowth into hydroxyapatite orbital implants in 4 weeks after the implantation.