玻璃体内注射辅酶Q10对NaIO3诱导的AMD模型小鼠的保护作用

目的　探讨玻璃体内注射水溶性CoQ10对NaIO₃诱导的年龄相关性黄斑变性（age-related macular degeneration，AMD）的保护作用。方法　66只昆明小鼠分为3组:对照组、NaIO₃诱导组（小鼠尾静脉注射NaIO₃）和CoQ10修复组，小鼠尾静脉注射NaIO₃后玻璃体内分别注射高浓度（2.0 g·L^-1）和低浓度（0.1 g·L^-1）的CoQ10，注射平衡液做假处理组。在建模后第7天取材，行常规组织切片、HE染色、GFAP染色、Iba1染色，检测NaIO₃诱导的视网膜病变和CoQ10对该种病变的修复效果。结果　注射NaIO₃ 7 d后，HE染色结果显示，NaIO₃诱导组小鼠视网膜外核层每10 μm 长度的细胞数由正常水平（29.13±3.97）个减少至（17.50±4.03）个，差异有统计学意义（P<0.01）；GFAP染色结果显示，Müller细胞发生反应性胶质化，与对照组相比每250 μm×250 μm面积的细胞数由（21.17±4.26）个增加至（28.67±2.80）个，差异有统计学意义（P<0.01）；Iba1染色结果显示，小胶质细胞呈现出“阿米巴状”的激活形态，每250 μm×250 μm面积的细胞数由（6.71±2.29）个增加至（22.14±3.76）个，差异有统计学意义（P<0.01）。分别对NaIO₃诱导组小鼠玻璃体内注射高、低浓度的CoQ10（2.0 g·L^-1和0.1 g·L^-1）后，与假处理组相比，其中注射高浓度CoQ10（2.0 g·L^-1）组外核层细胞数目显著增加（P<0.05），而低浓度CoQ10（0.1 g·L^-1）组没有显著差异（P>0.05）。并且，Müller细胞反应性胶质化程度减弱，GFAP阳性细胞数恢复至（23.83±3.87）个；小胶质细胞分枝增多，Iba1阳性细胞数恢复至（16.86±3.29）个，与NaIO₃诱导组相比，差异均有统计学意义（均为P<0.05）。结论　玻璃体内注射CoQ10可通过减轻Müller细胞的反应性胶质化和抑制小胶质细胞的激活而减缓视网膜感光细胞退化，对AMD起到保护作用。

Protective effect of intravitreal injection of coenzyme Q10 on NaIO3-induced age-related macular degeneration in model mice

Objective　To investigate the protective effect of water-soluble CoQ10 using intravitreal injection on age-related macular degeneration (AMD) induced by sodium iodate.Methods　Totally 66 Kunming mice were divided into three groups randomly:control group,NaIO₃ induced group,in which sodium iodate was injected into the tail veins of the mice;CoQ10 protection group,different dosage of CoQ10 (0.1 g·L^-1 and 2.0 g·L^-1) were used to recover this damage using intravitreal injection in sodium iodate induced mice,and balanced salt solution was injected to the sham operation group.On the 7th day of the injection,all of the mice’s eyeballs were obtained and then different operations of tissue sections,HE staining,GFAP staining and Iba1 staining were performed to detect the damage effects of sodium iodate and the effects of CoQ10.Results　After 7 days,in sodium iodate induced mice,HE stanning results showed that the cell numbers in 10 μm length of the outer nuclear layer (ONL) significantly decreased from (29.13±3.97)cells to (17.50±4.03)cells as compared with the control group (P<0.01);GFAP stanning showed that Müller cells exhibit reactive astrogliosis,and the cell numbers in 250 μm×250 μm were significantly increased from (21.17±4.26)cells to (28.67±2.80)cells compared to the control group (P<0.01),while the Iba1 stanning showed that microglial cells presented the activation form of amebocyte,and the cell numbers in 250 μm×250 μm significantly increased from (6.71±2.29)cells to (22.14±3.76)cells compared with the control group (P<0.01).Two concentrations of CoQ10 (0.1 g·L^-1 and 2.0 g·L^-1) were instantly exposed to vitreous chamber of the mice after sodium iodate injection.The ONL cell numbers in the high concentration CoQ10 (2.0 g·L^-1) group was significantly increased as compared to the sham-treated group (P<0.05).There was no significant difference in the low concentration CoQ10 (0.1 g·L^-1) group (P>0.05).Moreover,the degree of reactive gliosis of Müller cells was found to be weakened,and the number of GFAP positive cells was recovered to (23.83±3.87)cells,and the branches of microglial cells were increased while the number of Iba1 positive cells was restored to (16.86±3.29)cells,as compared to the induction group.The results of the two groups were compared and significant difference was found statistically (P<0.05).Conclusion　It is found that 2.0 g·L^-1 water-soluble CoQ10 shows a good protective effects on AMD using intravitreous injection,and CoQ10 plays an important role in reducing the reactive gliosis of Müller cells and inhibiting the activation of microglial cells to slow down the photoreceptor degeneration.