兔眼玻璃体内注射足叶乙苷对视网膜神经节细胞的毒性作用
Toxic effects of intravitreal injection of etoposide on retinal ganglion cells in rabbit eyes
摘要目的 观察兔眼玻璃体内注射足叶乙苷对视网膜神经节细胞(RGC)的毒性作用.方法 采用随机数字法将24只健康新两兰大白兔随机分为正常组和0.0、1.5、15.0、150.0、375.0、750.0、1500.0μg 足叶乙苷组,每组3只兔,每只兔双眼用于实验.正常组不作任何处理,其余各组兔眼玻璃体内分别注射0.0、1.5、15.0、150.0、375.0、750.0、1500.0 μg足叶乙苷.注射后12 d,空气栓塞法处死所有兔.取眼球作常规病理检查,苏木精-伊红(HE)染色,光学显微镜观察视网膜形态变化、计数视网膜颞侧距视盘颞侧缘1 mm处400倍视野的RGC数量.取距视盘1 mm处颞上方1 mmX 1 mm大小视网膜行常规透射电子显微镜检查,观察视网膜超微结构变化情况.结果 光学显微镜和透射电子显微镜观察发现,正常组兔眼视网膜结构清晰规整,RGC呈球形或类球形;0.0、1.5、15.0、150.0μg足叶乙苷组兔眼视网膜各层结构与正常组相似;375.0、750.0、1500.0μg足叶乙苷组兔眼视网膜明显变薄,层次结构紊乱.正常组、0.0、1.5、15.0、150.0、375.0、750.0、1500.0μg足叶乙苷组兔眼RGC计数分别为(61.66±3.72)、(61.83±4.59)、(60.00±7.07)、(62.00±4.43)、(62.67±3.98)、(7.33±1.37)、0.00、0.00个,8组间差异有统计学意义(F=145.04,P=0.00).0.0、1.5、15.0、150.0μg足叶乙苷组兔眼RGC计数较正常组无明显变化,差异无统计学意义(F=0.244,P>0.05);375.0μg足叶乙昔组兔眼RGC计数较正常组、0.0、1.5、15.0、150-0 μg 足叶乙昔组明显降低,差异有统计学意义(F=145.04,P<0.05).结论 足叶乙苷对兔眼RGC有一定毒性作用,且该作用呈剂量依赖性.
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abstractsObjective To observe the toxic effects of intravitreal injection of etoposide on retinal ganglion cells (RGC) in rabbit eyes. Methods Twenty-four healthy rabbits were divided into 8 groups randomly, including one normal group without any treatment, and 7 experimental groups with intravitreal injection of different dosages of etoposide (0.0, 1.5, 15.0, 150.0, 375.0, 750.0, 1500.0 μg). Twelve days after the injection, the animals were killed by air embolism, and the eyeballs were prepared for routine pathological examination with hematoxylin-eosin staining and transmission electron microscopy. Results Four experimental groups (0.0, 1.5, 15.0, 150.0 μg etoposide) had normal retinal structure and normal shape of ganglion cells while other 3 experimental groups with higher dosage of etoposide (375.0, 750.0 and 1500.0 μg) showed thinner and disorganized retina. The number of RGC of the normal group and 0.0, 1.5,15.0, 150.0, 375.0, 750.0, 1500.0 μg groups were 61.6±63.72, 61.83±4.59, 60.00±7.07, 62.00±4.43, 62.67±3.98, 7.33±1.37, 0.00 and 0.00 per 400 X visual field, with statistical difference among groups (F=145.04, P = 0.00). There was no statistical difference between the normal group and 0.0,1.5, 15.0, 150.0 μg groups (F=0.244,P>0.05). The number of RGC of 375.0 μg group was decreased obviously compared with normal group and 0.0, 1.5, 15.0, 150.0 μg groups with statistical difference (F=145.04, P<0.05). Conclusion Etoposide has a dosage-dependent toxicity on rabbit RGCs.
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