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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BrownNorway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ERGc波。结果:注射NaIO3后,高剂量组如30、40和60mg/kgNaIO3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3d30mg/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NaIO330mg/kg组和低剂量组未发现明显变化。体外实验发现,浓度≥30mg/LNaIO3组RPE-19细胞增殖率降低。注射剂量为35mg/kgNaIO3后4wk,和对照组相比,NaIO3组大鼠ERGc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ERGc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/kgNaIO3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。
OBJECTIVE: To investigate the antagonistic effect of 10g / L hydralazine eye drops on NaIO3-induced RPE degeneration in rats at a dose of 35mg / kg. Methods: Brown Norway rats were injected with NaIO3 and saline at different doses through the sublingual vein. The a, b, c, FO and LP of ERG were measured at 3, 7, 14 and 28 days after injection. Fluorescent angiography. Histological studies of some rats were performed with light microscopy or autofluorescence. RPE-19 cells were cultured in vitro, the effects of different concentrations of NaIO3 on the cells were observed and the cell proliferation rate was measured. Brown Norway rats were injected subcutaneously with NaIO3 at a dose of 35 mg / kg. Rats in NaIO3 group were injected with NaIO3, saline was injected into the eyes. 10g / L of hydralazine + NaIO3 group were injected with 10g / L hydralazine eye drops. NaIO3 was injected into the rats in the control group with normal saline. 3 times / d, continuous point 4wk, and then measured ERGc wave. Results: After injecting NaIO3, the amplitudes of various ERG waves in high dose group such as 30, 40 and 60 mg / kg of NaIO3 group were significantly lower than those in low dose group. Fundus color photographs showed partial retinal necrosis in the 30mg / kg group after NaIO3 injection. The degree of retinal necrosis was positively correlated with time and injection volume after injection, but no significant change was observed in the low dose group. Plain radiographs showed that monolayer RPE cells were necrotic at 30 mg / kg and higher doses after NaIO3 injection. Histological studies suggest that injection of NaIO330mg / kg group and low dose group did not find significant changes. In vitro experiments found that the concentration of ≥ 30mg / LNaIO3 group RPE-19 cell proliferation rate decreased. Compared with the control group, the ERGc wave of NaIO3 group was significantly reduced to 31% of the control group (P <0.01) at the injection dose of 35 mg / kg NaIO3 4 wk. Compared with NaIO3 group, the level of ERGc in 10g / L hydralazine + NaIO3 group was significantly increased to 50% of the control group (P <0.05). Conclusion: NaIO3-induced apoptosis of PRE cells is affected by both dose and time. The dose of 30 ~ 40mg / kgNaIO3 for non-exudative age-related macular degeneration in vivo modeling. Hydralazine may delay the progression of non-exudative age-related macular degeneration and may be used to treat non-exudative age-related macular degeneration.