摘要
目的探讨缺氧诱导因子-1a（hypoxia-inducible factor—1a，HIF—1a）在代谢性酸中毒诱导视网膜新生血管中的表达和意义。方法将120只新生SD大鼠随机分为酸中毒模型组和正常对照组，各60只。酸中毒模型组出生后第2天开始按535mg／（kg·d）的剂量管饲氯化铵溶液（质量浓度为50mg／ml），2次／d，连续6d，停药进入恢复期。2组大鼠分别于出生后第3、5、8、10、13、20天处死。二磷酸腺苷酶组织化学染色法观察新生大鼠视网膜血管的形态改变；HE染色观察视网膜血管增生情况，判断建模成功与否；免疫组织化学方法检测视网膜HIF—1a蛋白的表达变化。结果二磷酸腺苷酶组织化学染色法显示酸中毒模型组大鼠10日龄可见视网膜大量新生血管异常形成，周边可见大片无灌注区。HE染色可见酸中毒模型组新生大鼠10日龄视网膜突破内界膜血管内皮细胞核显著多于同龄对照组，分别为（28．78±7．53）个与（1．22±1．48）个，差异有统计学意义（t=11．169，P〈0．01）。免疫组织化学结果显示，酸中毒模型组新生大鼠8、10、13日龄时视网膜HIF-1a的表达强度分别为108．87±15．21、183．68±26．58和129．42±9．85，明显高于同龄对照组，分别为74．98±4．50、76．38±3．38和74．78±1．86，差异均有统计学意义（t=4．625、9．023和9．672，P均〈0．05）。结论HIF-1a在酸中毒诱导视网膜新生血管的发生、发展过程中可能发挥重要作用。
Objective To investigate the expression and significance of hypoxia-inducible factor-1a （HIF -1a） in the retinal neovascularization by metabolic acidosis in newborn rats. Methods One hundred and twenty newborn SD rats were randomly divided into acidosis （experiment） and normoxia （control） groups. A total of 60 newborn rats in experiment group underwent tubal feeding of NH4Cl at the dose of 535 mg/（kg · d） from the second day after birth, twice a day for 6 days and followed by a period of recovery. The rats in the two groups were sacrificed at the 3rd, 5th, 8th, 10th, 13th and 20th day after birth, respectively. The morphologic changes of retinal vessels were estimated by observing the vascular pattern in adenosine diphosphatase stained retina flat mounts. The newborn vessels were quantified by HE staining. Immunohistochemieal method was used to detect HIF-1a expression. Results In experiment group, numerous neovascufarization and un-perfused area at the periphery of vessels occurred on the 10th day. The result of HE staining showed that in experiment group of 10 day old, the number of neovascular nuclei extending into the vireo was 28. 78± 7.53, and that of the control group was 1.22 ±1.48 （t= 11. 169,P〈0. 01）. The results of immunohistochemistry revealed that the expression of HIF-1a protein were stronger in the experiment group than in the control group on the 8th, 10th and 13th day, and there were significant differences between the two groups （108. 87±15.21, 183. 68 ± 26.58 and 129.42 ± 9.85 vs 74.98±4.50, 76.38± 3.38 and 74.78±1.86, t=4.625, 9.023 and 9. 672,P〈0.05）. Conclusions HIF-1a might play an important role in retinal neovascularization.
出处
《中华围产医学杂志》
CAS
2011年第6期354-358,共5页
Chinese Journal of Perinatal Medicine
基金
基金项目：江苏省卫生厅科学基金资助项目（H200635）
关键词
视网膜新生血管化
缺氧诱导因子-1a
酸中毒
动物
新生
大鼠
Retinal neovascularization
Hypoxia-inducihle factor 1, alpha subunit
Acidosis
Animals, newborn
Rats
