雌激素对慢性高眼压模型大鼠视网膜神经节细胞凋亡的影响

Neuroprotective Effects of Estrogen on Retinal Ganglion Cells in Model Rats with Ocular Hypertension

目的探讨雌激素对慢性高眼压(elevated intraocular pressure,EIOP)模型大鼠视网膜神经节细胞(retinal ganglion cells,RGCs)的保护作用及可能的作用机制。方法 50只健康雌性SD大鼠随机分为正常对照组、高眼压模型组(去势+慢性高眼压+植物油)、实验组(去势+慢性高眼压模型+25、50、100μg·kg-1的17β-雌二醇皮下注射)。应用末端脱氧核酸转移酶介导的脱氧三磷酸尿昔缺口末端标记法(TUNEL法)及免疫组化法检测雌激素对视网膜神经节细胞凋亡及视网膜组织Bcl-2、Bax表达的影响。结果大鼠慢性高眼压模型组及实验组眼压明显高于正常对照组(P<0.05)。TUNEL染色结果表明,高眼压模型组及实验组TUNEL阳性细胞数较正常对照组增多,实验组阳性细胞数随雌激素浓度的升高逐渐减少。免疫组化结果显示,高眼压模型组大鼠视网膜Bcl-2蛋白的表达较正常对照组下降(P<0.05),实验组Bcl-2表达与正常对照组差异无统计学意义(P>0.05)。高眼压模型组及实验组Bax的表达与正常对照组比较均有增高,随着雌激素浓度升高,Bax蛋白表达程度呈现逐渐下调的递减趋势(P<0.05)。结论雌激素可能是通过升高Bcl-2、降低Bax蛋白的表达抑制慢性高眼压大鼠视网膜神经节细胞凋亡,从而发挥视神经保护作用。

Objective To observe the effects of estrogen on retinal ganglion cells apoptosis in rat model of chronic elevated intraocular pressure（ EIOP）. Methods 50 healthy female adult rats were randomly divided into normal group,high intraocular pressure（ EIOP） model group and experimental group（ 25μg ·kg^-1,50μg·kg^-1 and 100μg·kg- 117β- estrodiol）. The apoptosis of RGCs in retina was identified using TUNEL staining and the expressions of Bcl- 2,Bax protein were detected by immunohistochemistry. Results intraocular pressure（ IOP） of rat model significantly increased by unilaterally cauterizing episcleral vessels（ P〈0. 05）. TUNEL results showed that TUNEL positive cells in EIOP model group increased significantly compared with normal group,and the number of apoptosic cells decreased significantly with the concentration of estrogen in experimental group（ P〈0. 05）. The expression of Bcl- 2 in EIOP model group decreased significantly compared with other group（ P〈0. 05）,while expression of Bcl- 2 protein was no significantly difference between experimental group and normal group（ P〉0. 05）. The expression of Bax protein in EIOP model group increased significantly compare with normal group with increasing the concentration of estrogen while the expression of Bax protein decreased（ P〈0. 05）. Conclusion Estrogen can protect retinal ganglion cells in glaucoma rat against apoptosis by up- regulating the expression of Bcl- 2,down- regulating the expression of Bax.