糖皮质激素对糖尿病大鼠视网膜病变的影响

Effects of glucocorticoids on retina in diabetic rats

目的:探讨糖皮质激素对糖尿病(diabetes mellitu,DM)大鼠视网膜神经组织的损伤作用及机制。方法:利用链脲佐菌素诱导大鼠DM模型,玻璃体内注射腺病毒(DM组)或腺病毒包装的糖皮质激素受体反义寡核苷酸(si GR组)、阴性核苷酸序列(scRNA组)。另取正常SD大鼠,玻璃体腔注射腺病毒为对照组(CON组)。12wk后,HE染色检测视网膜神经节细胞(retinal ganglion cell,RGC)密度,测量大鼠视网膜厚度,免疫组织化学和Western-blot检测ROCK表达变化。结果:与CON组相比,DM组、si GR组及scRNA组糖皮质激素浓度均明显升高(均P<0.01)。HE染色显示,与CON组相比,DM组及scRNA组RGC密度明显降低,视网膜厚度下降,ROCK的蛋白表达增加(均P<0.01),而si GR组无明显变化(均P>0.05)。结论:抑制糖皮质激素能下调糖尿病大鼠视网膜ROCK表达,恢复视网膜RGC密度降低及视网膜厚度。

AIM：To investigate the effectand mechanism of glucocorticoids on retinal nerve tissue in diabetes mellitu（DM） rats.METHODS：The DM model was established by a single injection of streptozotocin.Diabetic rats were intravitreal injected with adenovirus vehicle（DM group）,or carried glucocorticoids receptor antisense（siGR group）,or scrambled nucleotide（scRNA group）.Control group（CON group） were normal SD rats intravitreal injected with adenovirus vehicle.Twelve weeks later,the density of retinal ganglion cell（RGC） and retinal thickness were detected by HE staining,and the expression of ROCK was observed by immunohistochemical staining and Western-blot.RESULTS：Compared with CON group,glucocorticoid concentrations were significantly increased in DM group,siGR group and scRNA group（P 〈0.01,respectively）.DM group and scRNA group showed reduction of RGC density and retinal thickness,and up-regulation of ROCK（P 〈0.01,respectively）.While no alterations was detected between CON group and siGR group（P〉0.05,respectively）.CONCLUSION：Inhibition of glucocorticoids in diabetes reverses the expression of retinal ROCK,RGC density,and retinal thickness.