氨基胍对糖尿病大鼠视网膜神经细胞改变及caspase-3表达的影响

The effect of aminoguanidine on retinal neurocyte and expression of caspase-3 on the diabetic rats

目的观察早期糖尿病大鼠视网膜神经细胞结构变化、caspase-3表达及氨基胍的治疗作用。方法健康成年Wistar大鼠50只,12只作为正常对照组,其他大鼠链脲佐菌素(streptozotocin,STZ)腹腔注射建立糖尿病(DM)大鼠模型,并随机分为氨基胍治疗组及DM模型组,每组又按时间分为1、3、6个月组。透射电镜下观察视网膜超微结构改变,免疫组织化学法检测视网膜组织caspase-3蛋白的表达变化。结果电镜变化:模型1个月组内核层细胞胞质出现不均匀现象;3个月组内核层细胞核个别染色质出现浓缩现象,神经节细胞亦出现超微结构的变化;6个月组上述变化进一步加重,并可在内核层及神经节细胞层发现个别凋亡小体,氨基胍治疗组变化较糖尿病组轻微。免疫组织化学表达:模型3个月组caspase-3蛋白开始表达,主要见于神经节细胞层;模型6个月组阳性表达进一步增加,扩展到内核层。氨基胍组caspase-3表达变化规律与模型组基本一致,治疗组3个月、6个月阳性表达均分别低于未治疗组(P<0·05)。结论早期DM大鼠视网膜出现了电镜组织学改变,caspase-3参与了糖尿病视网膜病变的发病机制。氨基胍对糖尿病视网膜病变有一定的治疗作用。

Objective To observe the effect of aminoguanidine on the change of retinal neurecyte and the expression of caspase-3 in diabetic rats. Methods Fifty adult Wistar rats were randomly divided into normal control group（ n = 12）and diabetic model group （38 were intraperitoneally injected with streptosotocin）. Thirty-six rats were successfully made into diabetic models and randomly divided into diabetes mellitus（DM） group and amlnoguanidine group. Diabetes and aminoguanidine groups were subdivided into 1,3,6 month groups according to the course of disease. The rats were killed at 1,3 and 6 month, observed by electromicroscope. The expression of caspase-3 was studied by strept avidin-biotin complex （SABC） immunohistocbemistry. Results Electromicroscope：In 1 month DM group, the ultrastructure change was slight. In 3 month DM group,nuclear condensation of visual cyte was observed in the inner nuclear cell layer. There was change in the ganglion cells. In 6 month DM group,apoptotic body was found in the inner nuclear cell layer and the ganglion cell layer. While in the treatment group, the situation was better. Immunohistochemistry：In 3 month DM group, positive expression of caspase-3 was found in ganglion cell layer. In 6 month DM group,positive expression was increased and extended to inner nuclear layer. In aminoguanidine group,the positive expression was less in comparison to that in DM group in the 3rd and 6th month （ P 〈 0. 05 ）. Conclusions Ultrastructural change of retina occurrs in early diabetic rats. Caspase-3 could play a role in the development of diabetic retinopathy. Aminoguanidine has certain therapeutic effect on diabetic retinopathy.