目的： 探讨褪黑素对大鼠糖尿病视网膜病变的影响及其机制。

方法： 选用健康雄性SD大鼠40只，随机分为4组，正常对照组、糖尿病组、低剂量褪黑素组和高剂量褪黑素组，HE染色观察视网膜结构改变，电镜观察视网膜神经节细胞超微结构变化，黄嘌呤氧化酶法检测视网膜组织中超氧化物歧化酶(SOD)及丙二醛(MDA)水平，Western Blot检测B细胞淋巴瘤-2(Bcl-2)，Bcl-2相关X蛋白(Bax)及P53的蛋白表达水平。

结果： HE染色结果显示，正常对照组大鼠视网膜组织结构清晰，糖尿病组大鼠视网膜组织层次欠清晰，神经纤维层水肿，低剂量褪黑素组视网膜细胞分层基本分明，层间细胞排列较整齐，内外核层排列稍紊乱，高剂量褪黑素组大鼠视网膜组织结构较低剂量褪黑素组进一步改善； 电镜观察结果显示，与糖尿病组比较，褪黑素组大鼠视网膜神经节细胞形态均不同程度改善； 黄嘌呤氧化酶法检测结果显示，褪黑素组大鼠视网膜组织中SOD水平高于糖尿病组，MDA水平低于糖尿病组(均P<0.05)； Western Blot结果显示，低、高剂量褪黑素组与糖尿病组比较，Bcl-2蛋白表达逐渐升高，Bax、P53蛋白表达明显降低(均P<0.05)。

结论：褪黑素可改善糖尿病大鼠视网膜形态变化，对糖尿病视网膜病变有一定抑制作用。

METHODS:Totally 40 healthy male SD rats were choose and randomly divided into 4 groups, normal control group, diabetid group, low dose melatonin group and high dose melatonin group. The changes of retinal structure were observed by hematoxylin-eosin staining(HE staining), ultrastructure of retinal ganglion cells were observed by electron microscopy, superoxide dismutase(SOD)and malondialdehyde(MDA)level in the retina tissue were detected by xanthine oxidase method, and protein expression levels of B cell lymphoma/lewkmia-2(Bcl-2), Bcl-2 associated X protein(Bax)and P53 were detected by Western Blot.

RESULTS: HE staining results showed that the rat retina tissue structure of the normal control group was clear, the retinal tissue of diabetes group rats were not clear, the nerve fiber layer was edema, the retina cells of low dose melatonin group were probably distinct, the interlayer cells were arranged neatly, and the inner and outer nuclear layers were slightly disordered, rats retinal structure in high dose melatonin group were further improved than that in low dose melatonin group; Electron microscope results showed that compared with diabetes group, retinal ganglion cells form in melatonin group were improved in different extent; Xanthine oxidase method detected that SOD level in retinal tissue of melatonin group rats were higher than that in diabetic group, the MDA level were lower than that in diabetic group, compared with diabetes group the differences both have statistically significant(P<0.05); Western blot results showed that the protein expression of Bcl-2 in low dose and high dose melatonin group gradually decreased, Bax and P53 protein expressions increased significantly, compared with diabetic group the differences were statistically significant(P<0.05).

CONCLUSION: Melatonin could improve the morphological changes of retina in diabetic rats and inhibit diabetic retinopathy to some extent.