TNF-α、IL-6对青光眼大鼠视网膜的影响

The Effect of TNF-αand IL-6 on the Retina of Glaucoma Rats

目的探究肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)对青光眼大鼠视网膜的影响。方法将64只3~5月龄的SD大鼠随机分为空白组、空白+TNF-α组、空白+IL-6组、空白+TNF-α+IL-6组、青光眼组、青光眼+TNF-α组、青光眼+IL-6组、青光眼+TNF-α+IL-6组,每组8只。各青光眼组动物在右眼复制青光眼模型,按分组给予TNF-α和(或)IL-6处理,比较各组造模前后,给药3、6周的眼压及视网膜组织病理和组织细胞凋亡情况。分离培养新生大鼠视网膜神经节细胞,并将其分为对照组、谷氨酸组、谷氨酸+TNF-α组、谷氨酸+IL-6组及谷氨酸+TNF-α+IL-6组,比较各组细胞的增殖与凋亡情况。结果给药6周,青光眼+TNF-α组眼压最高、视网膜组织细胞凋亡最明显,其次为青光眼组、青光眼+TNF-α+IL-6组和青光眼+IL-6组(均P<0.05),非青光眼各组眼压及视网膜组织细胞凋亡相当,差异无统计学意义(P>0.05);青光眼组、青光眼+TNF-α组、青光眼+IL-6组、青光眼+TNF-α+IL-6组视网膜神经节均存在病理改变,其中青光眼+TNF-α组细胞病变最为显著。视网膜神经节细胞被成功分离及培养;培养24~72 h,谷氨酸+TNF-α组增殖最弱,凋亡率最高,其次为谷氨酸组、谷氨酸+TNF-α+IL-6组和谷氨酸+IL-6组(均P<0.05)。结论IL-6可能具有保护青光眼所致视网膜细胞损伤的作用,或与抑制视网膜神经细胞TNF-α相关的炎性病变有关。

Objective To investigate the effect of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)on the retina of glaucoma model rats.Methods The 64 rats aged 3 to 5 months were randomly divided into the blank group,blank+TNF-αgroup,blank+IL-6 group,blank+TNF-α+IL-6 group,glaucoma group,glaucoma+TNF-αgroup,glaucoma+IL-6 group,glaucoma+TNF-α+IL-6 group,with 8 rats in each group.Half of the experimental animals were treated with TNF-αand/or IL-6.The intraocular pressure,retinal histopathology and cell apoptosis were compared before and after 3 and 6 weeks of treatment in each group.Retinal ganglion cells from neonatal rats were isolated and cultured.Those cells were divided into the control group,glutamate group,glutamate+TNF-αgroup,glutamate+IL-6 group and glutamate+TNF-α+IL-6 group.The cell proliferation and apoptosis of each group were compared.Results After 6 weeks of drug administration,the intraocular pressure and cell apoptosis in the glaucoma+TNF-αgroup were the highest,followed by the glaucoma group,the glaucoma+TNF-α+IL-6 group and the glaucoma+IL-6 group.The intraocular pressure and cell apoptosis of the other groups were equivalent,the difference was not statistically significant(P>0.05).Pathological changes of retinal ganglia cells were observed in the glaucoma group,glaucoma+TNF-αgroup,glaucoma+IL-6 group,glaucoma+TNF-α+IL-6 group,and the changes in glaucoma+TNF-αgroup were the most significant.Retinal ganglion cells were successfully isolated and cultured.After culturing for 24 h to 72 h,the glutamate+TNF-αgroup had the lowest proliferation and the highest cell apoptosis,followed by the glutamate group,glutamate+TNF-α+IL-6 group and glutamate+IL-6 group.The cell proliferation and apoptosis conditions of the other groups were similar,and the difference was not statistically significant(P>0.05).Conclusion IL-6 might have a protective effect on retinal cell damage caused by glaucoma,which might be related to the inhibition of TNF-αrelated inflammatory lesions in retinal nerve cells.