代谢性酸中毒诱导新生大鼠视网膜新生血管的实验研究

Metabolic-acidosis-induced retinal neovascularization

目的了解代谢性酸中毒诱导新生大鼠视网膜病变的发展进程,探讨其发生与血管内皮生长因子(VEGF)的关系。方法实验组新生Sprague-Dawley大鼠425只。从大鼠出生后第2天开始按535mg/kg的剂量管饲NH4Cl(浓度为50mg/ml),每天2次,管饲6d,然后进入恢复期。另选150只新生大鼠未进行管饲,作为对照组。两组大鼠分别于出生后3、5、8、10、13、20d处死。取出双眼进行视网膜铺片和二磷酸腺苷酶染色,对视网膜血管进行评估;用酶联免疫分析法进行VEGF的测定。结果实验组鼠在出生后3、5、8、10、13、20d的新生血管(NV)发生率分别为0%、9%、26%、55%、19%、0%。出生后第3天,实验组鼠VEGF的蛋白水平[(101.1±14.2)pg/mg]比对照组[(133.2±15.9)pg/mg]下降(P=0.004),出后生第8天,实验组鼠VEGF蛋白水平[(98.4±19.2)pg/mg]比对照组[(78.1±8.7)pg/mg]升高(P=0.028);出生后第5、10、13、20天,两组差异无统计学意义(P>0.05)。结论代谢性酸中毒可能损害了正在发育的视网膜血管而引起新生血管;酸中毒引起的视网膜新生血管与VEGF有关。

Objective To detect the development of retinal neovascularization （NV） induced by metabolic acidosis in neonatal rats and investigate the relationship between the occurrence of NV and vascular endothelial growth factor （VEGF）. Methods A total of 425 newborn Sprague-Dawley rats in experimental group underwent tubal feeding of NH4Cl （535 mg/kg） with the concentration of （50 mg/ml） （twice per day） from the 2nd day after the birth for 6 days and followed by a period of recovery. Additional 150 neonatal rats were in the control group without the tubal feeding. The rats were executed at the 3rd, 5th, 8th, 10th, 13th, 20th day after birth respectively. The retinal vessels were evaluated through retinal stretched preparation andadenosine diphosphatase （ADPase） staining; VEGF in retina was detected by enzyme linked immunosorbent assay （ELISA）. Results In the experimental group, the incidence of retinal NV at the 3rd, 5th, 8th, 10th, 13th, 20th day after birth was 0%,9%,26%,55%, 19G, and 0% respectively. At the 3rd day, the expression of VEGF protein was lower in experimental group [（101.1±14.2 ）pg/mg] than that in the control group [（133.2±15.9） pg/mg] （P=0. 004）, while at the 8th day it was higher in experimental group [（98.4±19.2） pg/mg] than that in the control group [（78.1±8.7） pg/mg] （P 0.028）. There was no significant difference between the two groups at the 5th, 10th, 13th, and 20th day （P〉0.05）. Conclusions Metabolic acidosis may induce NV by injuring the developing retinal vessels. Retinal NV induced by acidosis relates to VEGF.