糖皮质激素对糖尿病大鼠视网膜神经元再生的影响

目的：探讨糖皮质激素对糖尿病(diabetes mellitus，DM)大鼠视网膜神经元的损伤作用。

方法：选取清洁级雄性SD大鼠，腹腔注射链脲佐菌素建立DM模型，利用二甲基亚砜(dimethyl sulfoxide，DMSO)配置RU486溶液。DM模型建立成功后，腹腔注射糖皮质激素受体拮抗剂RU486为RU486治疗组，腹腔注射DMSO为糖尿病组。正常大鼠腹腔注射DMSO为对照组。3mo后，检测大鼠体质量、血糖、血清糖皮质激素(glucocorticoid，GC)浓度，HE染色检测视网膜神经节细胞(retinal ganglion cell，RGC)密度，利用Western blot和免疫荧光结合光密度值分析的方法，对神经元轴突再生标志物生长相关蛋白-43(growth associated protein-43，GAP-43)及突触数量标志物突触素(synaptophysin，SYN)的表达进行半定量分析。

结果：与对照组相比，糖尿病组大鼠血糖明显升高，体质量明显下降，血清GC浓度明显升高，RGC密度明显降低，视网膜GAP-43表达增强，SYN表达明显减弱(均P<0.01)； 与糖尿病组相比，RU486组RGC密度明显增加，视网膜GAP-43和SYN表达明显增强(均P<0.01)。

结论：拮抗GC的作用可能促进了糖尿病大鼠视网膜神经元轴突再生，增加了突触数量，恢复了视网膜RGC密度，结果提示GC长期升高可能参与了糖尿病视网膜病变的发生发展。

Effect of glucocorticoid on the retinal neurons of diabetes mellitus rats

AIM: To investigate the detrimental effect of glucocorticoid(GC)on the retinal neurons of diabetes mellitus(DM)rats.

METHODS: The DM model was induced by intraperitoneal injection(IP)of streptozotocin in adult male rats, and the solution of RU486 was configured with dimethyl sulfoxide(DMSO). RU486 treatment group with glucocorticoid receptor antagonist RU486 and diabetic group with DMSO by intraperitoneal injection was in successful DM model. Naive rats were injected with DMSO as control group. Three months later, we detected the body weight and blood glucose and GC concentration of serum. The changes of retinal ganglion cell(RGC)density was investigated by HE staining. The expression of growth associated protein-43(GAP-43, a marker of neuronal axon regeneration)and synaptophysin(SYN, a marker of synaptic number)were semi-quantity analyzed by the optical density of immunofluorescence and Western blot.

RESULTS:Compared with the control group, the body weight and density of RGC and expression of SYN in diabetic group were significantly lower(P<0.01), the blood glucose and GC concentration of serum and expression of GAP-43 in diabetic group were significantly higher(P<0.01). Compared with the diabetic group, the density of RGC and expression of GAP-43, SYN in RU486 group were significantly higher(P<0.01).

CONCLUSION: Inhibition of GC could ameliorate the axonal degeneration of retinal neurons in diabetic rats, and loss of the number of synapses, and restore the RGC density of retina. The results suggest that long-term elevation of GC may be involved in the occurrence and development of diabetic retinopathy.