摘要
目的：研究血管紧张素Ⅱ（AngⅡ）对内皮祖细胞（EPC）促血管新生主要因子HIF1a、VEGF基因表达的影响以及AT1受体阻滞剂的干预效果。方法：分离人脐血单个核细胞，在VEGF和bFGF存在条件下培养7-8d得到EPC；随机分对照组、AngⅡ组（10^-6mol·L^-1）、AngⅡ＋氯沙坦预处理组。半定量RT-PCR检测EPC内血管紧张素原（ATG）mRNA表达情况；血管紧张素受体AT1、AT2以及HIF1a、VEGFmRNA表达水平。结果：人脐血EPC表达AT1受体、AT2受体，不表达ATG。外源性AngⅡ作用后，EPC的AT1受体、AT2受体mRNA表达量较对照组显著增加（P〈0.05）；HIF1a、VEGF mRNA表达量较对照组显著降低（P〈0．05）。用氯沙坦预处理细胞后再用AngⅡ刺激，与单纯AngⅡ刺激组比较，HIF1a、VEGF mRNA表达明显增加。结论：RT-PCR结果显示，人脐血来源的EPC不表达血管紧张素原基因，因而不能产生内源性AngⅡ；外源性AngⅡ通过AT1／AT2受体下调EPC的促血管新生主要因子HIF1a和VEGF的表达，但详细机制尚需进一步研究。
Objective： To investigate the effect of ARB on Angiotensin Ⅱ（AngⅡ）-induced HIF1a and VEGF mRNA expression alteration in endothelial progenitor cells（EPC）. Methods： EPCs were isolated from human umbilical cord blood and characterized. After 7-8 days of culture, several groups of attached cells were incubated with AngⅡ（10^-6mol·L^-1）, AngⅡ＋ lorsartan （10^-6mol·L^-1）. Reverse transcription （RT）-polymerase chain reaction （PCR） were used to assess angiotensinogen, angiotensin type 1 receptor （AT1）, AT2, HIF1a, VEGF mRNA expression. Results：Our data indicated that human EPC did not express angiotensinogen, although they express AT1 and AT2. Angiotensin Ⅱ can significantly increase the AT1, AT2 mRNA expression ; these effects can be attenuated by pre-treatment with losartan. Angiotensin Ⅱ can apparently diminish HIF1a and VEGF mRNA expression, although the effect can be reduced by pre-treatment with losartan. Conclusion： Human EPC does not express angiotensinogen, that is, can not generate endogeneous angiotensin Ⅱ. ARB can reduce exogenous angiotensin Ⅱ induced the major angiogenic factors HIF1a and VEGF down-regulation partially through ATR, which mechanism still needs further investigation.
出处
《中国临床医学》
北大核心
2008年第4期441-444,共4页
Chinese Journal of Clinical Medicine
基金
国家重点基础研究发展计划(973计划)(项目项目编号:2007CB512003)
