国际眼科杂志
國際眼科雜誌
국제안과잡지
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
2008年
8期
1504-1510
,共7页
江伟%Wan-Yu Zhang%邱春亿
江偉%Wan-Yu Zhang%邱春億
강위%Wan-Yu Zhang%구춘억
视网膜色素上皮细胞%碘酸钠%年龄相关性黄斑变性%胼酞嗪
視網膜色素上皮細胞%碘痠鈉%年齡相關性黃斑變性%胼酞嗪
시망막색소상피세포%전산납%년령상관성황반변성%변태진
retinal pigment epithelium%sodium iodate%age-related macular degeneration%hydralazine
目的:研究10g/L胼酞嗪滴眼液对剂量为35mg/kg的NaIO3诱导的大鼠RPE变性的对抗作用.方法:经舌下静脉予Brown Norway大鼠分别注射不同剂量的NaIO3及生理盐水,注射3,7,14及28d后测量ERG的a、b、c、FO及LP波,同时进行眼底彩照和眼底荧光血管造影检查.用光学显微镜或自体荧光平片对部分大鼠进行组织学研究.在体外培养RPE-19细胞,观察不同浓度的NaIO3对细胞的影响并测其细胞增殖率.经舌下静脉予Brown Norway大鼠注射剂量为35mg/kg的NaIO3.NaIO3组大鼠注射NaIO3后用生理盐水点眼,10g/L胼酞嗪+NaIO3组大鼠注射NaIO3后用10g/L胼酞嗪滴眼液点眼,对照组不注射NaIO3,用生理盐水点眼,皆为3次/d,连续点4wk,然后测ERG c波.结果:注射NaIO3后,高剂量组如30、40和60mg/kg NaIO3组的各种ERG波的振幅明显降低,低剂量组则变化不大.眼底彩照显示注射NaIO3后3d 30mg/kg组出现部分视网膜坏死,视网膜坏死程度与注射后时间及注射量呈正相关,低剂量组没有明显改变.平片显示,注射NaIO3后3d30mg/kg组及更高剂量组单层RPE细胞出现坏死.组织学研究提示,注射NaIO3,30mg/kg组和低剂量组未发现明显变化.体外实验发现,浓度≥30mg/L NaIO3组RPE-19细胞增殖率降低.注射剂量为35mg/kg NaIO3后4wk,和对照组相比,NaIO3组大鼠ERG c波显著降低到对照组的31%(P<0.01).10g/L胼酞嗪+NaIO3组和NaIO3组相比,大鼠ERG c波显著升高到对照组的50%(P<0.05).结论:NaIO3诱导的PRE细胞凋亡受剂量和时间的双重影响.剂量为30～40mg/kg NaIO3适用于非渗出型年龄相关性黄斑变性的体内造模.胼酞嗪可能延缓非渗出型年龄相关性黄斑变性的发展进程,可能用于治疗非渗出型年龄相关性黄斑变性.
目的:研究10g/L胼酞嗪滴眼液對劑量為35mg/kg的NaIO3誘導的大鼠RPE變性的對抗作用.方法:經舌下靜脈予Brown Norway大鼠分彆註射不同劑量的NaIO3及生理鹽水,註射3,7,14及28d後測量ERG的a、b、c、FO及LP波,同時進行眼底綵照和眼底熒光血管造影檢查.用光學顯微鏡或自體熒光平片對部分大鼠進行組織學研究.在體外培養RPE-19細胞,觀察不同濃度的NaIO3對細胞的影響併測其細胞增殖率.經舌下靜脈予Brown Norway大鼠註射劑量為35mg/kg的NaIO3.NaIO3組大鼠註射NaIO3後用生理鹽水點眼,10g/L胼酞嗪+NaIO3組大鼠註射NaIO3後用10g/L胼酞嗪滴眼液點眼,對照組不註射NaIO3,用生理鹽水點眼,皆為3次/d,連續點4wk,然後測ERG c波.結果:註射NaIO3後,高劑量組如30、40和60mg/kg NaIO3組的各種ERG波的振幅明顯降低,低劑量組則變化不大.眼底綵照顯示註射NaIO3後3d 30mg/kg組齣現部分視網膜壞死,視網膜壞死程度與註射後時間及註射量呈正相關,低劑量組沒有明顯改變.平片顯示,註射NaIO3後3d30mg/kg組及更高劑量組單層RPE細胞齣現壞死.組織學研究提示,註射NaIO3,30mg/kg組和低劑量組未髮現明顯變化.體外實驗髮現,濃度≥30mg/L NaIO3組RPE-19細胞增殖率降低.註射劑量為35mg/kg NaIO3後4wk,和對照組相比,NaIO3組大鼠ERG c波顯著降低到對照組的31%(P<0.01).10g/L胼酞嗪+NaIO3組和NaIO3組相比,大鼠ERG c波顯著升高到對照組的50%(P<0.05).結論:NaIO3誘導的PRE細胞凋亡受劑量和時間的雙重影響.劑量為30～40mg/kg NaIO3適用于非滲齣型年齡相關性黃斑變性的體內造模.胼酞嗪可能延緩非滲齣型年齡相關性黃斑變性的髮展進程,可能用于治療非滲齣型年齡相關性黃斑變性.
목적:연구10g/L변태진적안액대제량위35mg/kg적NaIO3유도적대서RPE변성적대항작용.방법:경설하정맥여Brown Norway대서분별주사불동제량적NaIO3급생리염수,주사3,7,14급28d후측량ERG적a、b、c、FO급LP파,동시진행안저채조화안저형광혈관조영검사.용광학현미경혹자체형광평편대부분대서진행조직학연구.재체외배양RPE-19세포,관찰불동농도적NaIO3대세포적영향병측기세포증식솔.경설하정맥여Brown Norway대서주사제량위35mg/kg적NaIO3.NaIO3조대서주사NaIO3후용생리염수점안,10g/L변태진+NaIO3조대서주사NaIO3후용10g/L변태진적안액점안,대조조불주사NaIO3,용생리염수점안,개위3차/d,련속점4wk,연후측ERG c파.결과:주사NaIO3후,고제량조여30、40화60mg/kg NaIO3조적각충ERG파적진폭명현강저,저제량조칙변화불대.안저채조현시주사NaIO3후3d 30mg/kg조출현부분시망막배사,시망막배사정도여주사후시간급주사량정정상관,저제량조몰유명현개변.평편현시,주사NaIO3후3d30mg/kg조급경고제량조단층RPE세포출현배사.조직학연구제시,주사NaIO3,30mg/kg조화저제량조미발현명현변화.체외실험발현,농도≥30mg/L NaIO3조RPE-19세포증식솔강저.주사제량위35mg/kg NaIO3후4wk,화대조조상비,NaIO3조대서ERG c파현저강저도대조조적31%(P<0.01).10g/L변태진+NaIO3조화NaIO3조상비,대서ERG c파현저승고도대조조적50%(P<0.05).결론:NaIO3유도적PRE세포조망수제량화시간적쌍중영향.제량위30～40mg/kg NaIO3괄용우비삼출형년령상관성황반변성적체내조모.변태진가능연완비삼출형년령상관성황반변성적발전진정,가능용우치료비삼출형년령상관성황반변성.
·AIM: To study the effects of 10g/L hydralazine eye drops on 35mg/kg NaIO3-induced degeneration in rat eyes. · METHODS: Various doses of NalO3 and/or saline alone were injected into Brown Norway rats from hypoglossal vein. After 3, 7, 14 or 28 days of injection, ERG a-, b-, c- wave, fast oscillation (FO) and light peak (LP) were measured along with retinal colored pictures and fluorescein angiography taken. Some rats were chosen to study the histology of retinas by light microscopy and autofluorescence of retina flatmounts. Different concen- trations of NaIO3 were given to RPE-19 cells, and cell proliferation rate was measured. For hydralazine study, 35mg/kg NaIO3 was injected into Brown Norway rat from hypoglossal vein. NaIO3 group was treated with saline alone after NaIO3 injection, 10g/L hydralazine + NaIO3 group was treated with 10g/L hydralazine eyedrops after NaIO3 injection whereas normal group was treated with saline alone without NalO3 injection. All eyedrops were instilled locally 3 times a day for 4 weeks and ERG c-wave was measured at the end of 2 and 4 weeks.· RESULTS: After NaIO3 administration, the amplitude of all ERG waves fell markedly in large dose groups at 30, 40 or 60mg/kg NaIO3. Not many changes were observed in groups treated with < 30mg/kg NaIO3. Some retinal necrosis appeared from 3 days post-injection (PI) in 30mg/kg NaIO3 group, which became more serious in larger dose groups or longer treatment time, but no apparent change was found in smaller dose groups. Similarly, on the retina flatmount, RPE monolayer showed necrosis from 3 days PI in the 30mg/kg NaIO3 and larger dose groups. On histological examination, no significant change was seen in 30mg/kg NaIO3 and lower concentration groups. In cell culture experiment, changes were found in RPE-19 cells proliferation rate with a concentration of NaIO3 at 30mg/L or higher. In hydralazine experiments, 4 weeks after injection of NaIO3, ERG c-wave fell markedly in NaIO3 group to 31% of control group (P < 0.01). The ERG c-wave of hydra- lazine + NaIO3 group fell only to 50% of control group (P<0.05). This was a 61% reversal of the c-wave of NaIO3 treated group. · CONCLUSION: RPE degeneration induced by NaIO3 was both dose and time dependent. Around 30 to 40 mg/kg NaIO3 would be the optimal to be used as a non-exudative age-related macular degeneration rat model. Hydralazine may postpone the development of non-exudative age- related macular degeneration.
