血管内皮生长因子对胎鼠肺组织基质金属蛋白酶2及基质金属蛋白酶9表达的影响

Effect of vascular endothelial growth factor on the expressions of matrix metalloproteinase-2 and metalloproteinase-9 in lung tissues of embryonal rats

目的:探讨血管内皮生长因子(VEGF)对胎鼠肺组织基质金属蛋白酶2(MMP-2)及基质金属蛋白酶9(MMP-9)表达的影响及调控作用。方法:取孕龄16d清洁SD大鼠30只,随机分为3组,生理盐水对照组(对照组)、VEGF低剂量组和VEGF高剂量组,每组10只。VEGF低剂量组每只孕鼠给予VEGF0.5μg,VEGF高剂量组每只孕鼠给予VEGF1μg,对照组给予生理盐水1mL/kg,术后置于清洁笼中常规喂养。于用药后3d,剖宫取出胎鼠。应用免疫组织化学和半定量RT-PCR方法分别检测胎鼠肺组织MMP-2和MMP-9蛋白及mRNA的表达情况。结果:对照组MMP-2蛋白和mRNA的表达相对值分别为120.23±10.93和0.33±0.08;MMP-9蛋白和mRNA的表达相对值分别为113.07±8.11和0.21±0.04。VEGF低剂量组MMP-2蛋白(138.17±12.32)、mRNA(0.65±0.15)和MMP-9蛋白(130.22±11.12)、mRNA(0.60±0.09)表达有一定程度的增高(P<0.05);VEGF高剂量组的各项表达量均明显增高(P<0.01)。结论:VEGF可上调胎鼠肺组织中MMP-2和MMP-9蛋白及mRNA的表达水平,可促进胎鼠的肺部发育。

Objective To investigate the effect of vascular endothelial growth factor （VEGF） on the expressions of metalloproteinase-2 （MMP-2） and metalloproteinase-9 （MMP-9） in lung tissues of embryonal rats. Methods 30 SD rats with 16 days of pregnancy were randomly assigned to receive 1 mL/kg normal saline （control group, n = 10）, 0.5μg VEGF （VEGF low-dose group, n=10）, or 1μg VEGF （VEGF high-dose group, n = 10）, then received cesarean section 3 days after treatment. The expressions of MMP-2 and MMP-9 protein were measured by immunohistochemistry, MMP-2 and MMP-9 mRNA were measured by RT-PCR in lung tissue of embryoual rats. Results As compared with control group, the expressions of MMP-2 protein and mRNA were significantly higher （138.17 ±12.32 vs 120.23 ± 10.93, 0.65 ±0.15 vs 0.33±0.08, P 〈 0.05）, and the expressions of MMP-9 protein and mRNA were also significantly higher in VEGF lowdose group （130.22 ±11.12 vs 113.07± 8.11, 0.60 ±0.09 vs 0.21 ± 0.04, P〈 0.05）. The expressions of MMP-2 and MMP-9 protein and mRNA were significantly higher in VEGF high-dose group （P 〈 0.01）. Conclusion The expressions of MMP-2 and MMP-9 protein and mRNA in lung tissues of embryonal rats can be up-regulated by VEGF, which may promote the pulmonary growth.