糖尿病大鼠早期视网膜小胶质细胞活化与神经节细胞损害的关系

Microglial activation and ganglion cells damages in the rat retina with early stage streptozotocin-induced diabetes

目的 观察糖尿病早期视网膜小胶质细胞的活化特征与视网膜神经节细胞（RGC）损害的关系.方法 20只成年雄性Sprague-Dawley（SD）大鼠,采用链脲佐菌霉素腹腔注射方法制作糖尿病动物模型,分为糖尿病1、3个月组及相应正常对照组,每组5只大鼠.对所有大鼠行上丘定位注射逆行标记RGC,分别用免疫组织化学法标记视网膜铺片、冰冻切片小胶质细胞和RC-C,共聚焦显微镜下观察小胶质细胞细胞形态及分布特征.结果 糖尿病组视网膜铺片小胶质细胞胞体增粗,形态不规则.与对照组相比,糖尿病3个月组RGC层发生吞噬的小胶质细胞密度显著增加（t=3.83,P〈0.01）.与对照组相比,糖尿病大鼠1、3月个组RGC层小胶质细胞平均密度均显著增加（t=2.71,4.22 P〈0.05） 糖尿病大鼠3个月组RGC层小胶质细胞平均密度较糖尿病1个月组显著增加（t=7.45,P〈0.0001）.糖尿病早期小胶质细胞与RGC数量之间存在相关关系（r=0.9,P〈0.05）.结论 糖尿病早期小胶质细胞活化与RGC损伤关系密切.

Objective To observe the relationship between retinal microglial activations and ganglion cell （RGC） damages in early-stage diabetic rats. Methods A total of 20 Sprague-Dawley（SD）rats were randomly divided into 4 groups （each with 5 rats）： 1 month control group, 1 month diabetes group, 3 month control group, 3 month diabetes group. Diabetes was induced by intraperitoneal injection of streptozotocin （STZ）. The RGCs of all rats were retrograde labeled by carbocyanine dye DiI injected at the superior colliculi. Microglial cells and RGCs in retinal flat-mounts and sections were stained immunohistochemically and recorded under confocal microscope. Results The diabetic microglial cells were amoeboid and ovoid with fewer processes on retinal flat-mounts. The density of microglial cells which phagocytosed Dil particles in the RGC layer significantly increased in the 3-month diabetes group（P〈0.01）. The density of microglial cells in the RGC layer significantly increased in the 1- and 3- month diabetes group （P〈0. 05）. However there were more microglial cells in the RGC layer in the 3-month diabetes group than the 1-month diabetes group （P 〈 0.0001 ）. Significant correlation was found between the amount of microglial cells and that of RGCs in the early-stage of diabetes. Conclusions Microglial cell activation has close relationship with the RGC damages in early-stage diabetic rats.