链脲佐菌素诱发糖尿病大鼠模型视网膜形态学改变的观察

Morphological changes in diabetic rat’s retina induced by streptozotocin

目的研究链脲佐菌素(streptozotocin,STZ)诱发SD大鼠糖尿病的视网膜形态学改变,为STZ诱发的糖尿病大鼠作为糖尿病视网膜病变动物模型提供依据。方法20只成年SD大鼠随机分为2组,A组用STZ腹腔注射法诱发糖尿病,B组作为正常对照。用葡萄糖氧化酶法在建模后1d、2d、3d、1周、2周、3周、4周连续测定大鼠血糖,在建模当天及建模后1周、2周、3周、4周用电子天平连续测量大鼠体质量,判断糖尿病发生的有效性和稳定性。通过临床和实验方法(包括裂隙灯检查,直接、间接眼底镜检查,4周时行组织切片、视网膜血管铺片、透射电镜等方法)检查大鼠眼前后节的病理改变。结果A组大鼠血糖在注射STZ后1d达到(33.9±1.7)mmol·L-1,在4周时达到(41.6±4.5)mmol·L-1,而B组始终低于16.7mmol·L-1。从建模之后,A组大鼠的体质量与B组相比,增长缓慢,有显著统计学意义。临床检查,A组1只糖尿病大鼠在4周时发生了白内障,B组大鼠眼前后节没有明显改变。发病4周时,组织学检查显示,A组大鼠视网膜厚度要薄于B组,透射电镜显示A组大鼠视网膜各层结构有明显的病理改变包括膜盘间隙扩大、排列紊乱、内外核层细胞疏松等,血管铺片显示4周A组大鼠视网膜毛细血管周细胞数量减少。结论用STZ方法建立糖尿病模型是有效的,发病4周时糖尿病大鼠已经有较明显的视网膜形态学改变,能够作为糖尿病视网膜病变模型用于临床和科研。

Objective To study the morphological degeneration in STZ diabetic rats retina induced by streptozotocin （STZ） and provide evidence as diabetic retinopathy model. Methods Twenty SD rats were randomly divided into two groups, Group A with diabete induced by STZ intraperitoneal injection and Group B as control. Blood glucose concentration and body weight were determined at 1 day,2 days,3 days,1 week,2 weeks,3 weeks,4 weeks after intraper- itoneal injection. Pathological changes of anterior and posterior module were examined with clinical and experimental methods, such as slit lamp, direct and indirect ophthalmoscopy, make histological section at 4 weeks, retinal vessels stretched preparation and transmission electron microscope. Results The blood glucose level ofGroup A was （33.9 ± 1.7） mmol· L-1 at the 1st day after intraperitoneal injection and （41.6 ± 4.5 ）mmol · L-1 at 4 weeks,while the Group B stably under 16.7 mmol · L-1. The bodyweight of Group A was lower than Group B. There was 1 rat in Group A with cataract at 4 weeks, while no change was found in anterior and posterior nodule of Group B. The thickness of retina in Group A was thinner than that in Group B with histological Qamination at 4 weeks after intraperitoneal injection; The transmission electron microscope showed there were disorders in the retinal neure, gap enlarged between membranous disc and cell decreased at exterior and interior nuclear layer. The reti- nal vascular preparation showed perivascular cells reduced. Conclusion The diabetes induced by STZ is efficiently and stably,and 4 weeks STZ diabetic rats have significant retinal degeneration in retinal vessels and neure. The STZ diabetic rats may be used as madels in the research of diabetic retinopathy. [ Rec Adv Ophthalmol 2008 ;28 （8） ：583-585,589 ]