| 摘要: |
| 目的 观察链脲佐菌素(STZ)诱导糖尿病(DM)大鼠早期视网膜的形态学改变，评价该方法作为早期糖尿病视网膜病变(DR)动物模型的可行性。方法 64只体质量(180±20) g的雄性SD大鼠随机均分为CON组、DM组(n=32)，DM组按60 mg/kg体质量腹腔注射1%STZ 1次建立DM大鼠模型；CON组腹腔注射等量柠檬酸缓冲液作为对照。注射前DM组、CON组平均体质量、血糖水平差异均无统计学意义。DM成模后每周测量各组体质量、血糖等一般生理指标。成模后第10周，各组随机抽样对视网膜组织进行H-E染色、FITC-dextran灌注视网膜血管铺片及透射电镜超微结构观察。结果 STZ腹腔注射诱导DM成模率100％。STZ腹腔注射后，DM组体质量增加不明显，后期甚至有所减轻；CON组体质量逐步增长，10周时DM组体质量明显低于CON组 \[(169.9±26.9) g vs (439.2±23.5) g,P<0.001\]。STZ腹腔注射72 h后，DM组血糖明显高于CON组\[(26.63±4.54) mmol/L vs (6.37±0.49) mmol/L,P<0.001\]，至第10周DM组血糖均>16.7 mmol/L，CON组保持在5.6～7.4 mmol/L。H-E染色显示DM组大鼠视网膜毛细血管扩张，间质水肿；CON组视网膜未见明显异常。FITC-Dextran灌注视网膜显示DM组血管迂曲，管径不规则，未见毛细血管荧光渗漏、微血管瘤、视网膜无灌注区等；CON组血管管径均匀一致、分支自然流畅。透射电镜下DM组视网膜超微结构的改变主要有：毛细血管基底膜增厚，内皮细胞指状突起，线粒体肿胀、嵴脱落、空泡样变，周细胞线粒体肿胀、嵴脱落；内核层双极细胞线粒体肿胀、嵴脱落、空泡样变；感光细胞膜盘间隙增宽、数量减少；神经节细胞线粒体肿胀、嵴脱落、空泡样变。CON组视网膜超微结构未见明显异常改变。结论 STZ诱导的DM大鼠在病程10周时即已出现类似人类早期背景型糖尿病视网膜病变(BDR)的相关形态学改变，可作为早期DR的动物模型以用于相关研究，且该方法简单经济、用时较短、重复性好、成功率高。 |
| 关键词: 糖尿病 视网膜 动物模型 链脲佐菌素 |
| DOI：10.3724/SP.J.1008.2010.01049 |
| 投稿时间：2010-05-12修订日期：2010-07-19 |
| 基金项目:国家自然科学基金青年科学基金(30801268), 第二军医大学灾害医学基金. |
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| Streptozotocin-induced early diabetic retinopathy model in rats |
| GAO Yu1,LIU Lin2,Wu Jin-Hui2* |
| (1. Department of Ophthalmology, No. 411 Hospital of PLA, Shanghai 200081, China;2. Department of Ophthalmology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| Objective To observe the morphological changes of the retina at early stage of streptozotocin (STZ)-induced diabetes mellitus (DM) model, so as to assess the feasibility of using STZ-induced DM as an animal model of early diabetic retinopathy (DR). Methods Sixty-four male SD rats (body weight \[180±20\] g) were randomly divided into the CON and DM groups (n=32). Rats in DM group received intraperitoneal injection of 1% STZ once and those in the CON group were given same volume of citrate buffer in the same manner. The average body weight and blood glucose were similar in the two groups before intraperitoneal injection. The blood glucose, body weight, and other parameters were determined once a week after intraperitoneal injection. In the 10th week, the morphological changes of the retina were observed by H-E staining, stretched preparation of FITC-dextran perfused retinal blood vessels, and transmission electron microscopy in randomly chosen samples. Results The successful rate of STZ-induced DM model was 100%. The body weight of animals in DM group had no obvious increase after injection, and it even decreased at late stage. The body weight increased gradually in the CON group. The average body weight of DM group (\[169.9±26.9\] g) was significantly lower than that of the CON group (\[439.2±23.5\] g) in the 10th week (P<0.001). The average blood glucose of DM group (\[26.63±4.54\] mmol/L) was significantly higher than that of the CON group (\[6.37±0.49\] mmol/L) 72 h after injection (P<0.001). DM group had a blood glucose > 16.7 mmol/L and CON group had a blood glucose of 5.6-7.4 mmol/L throughout the 10 weeks. Retina H-E staining showed retinal capillary dilatation and interstitial edema in DM group in the 10th week, and the CON group had no obvious abnormalities. Stretched preparation of FITC-Dextran perfused retinal blood vessels showed vascular tortuosity and caliber irregularity in the DM group, but with no leakage, microvascular tumor or retinal non-perfusion area. The retinal vessel diameter was uniform and the branching was natural and smooth in the CON group. TEM results showed the following retinal ultrastructural changes in the DM group: thicker capillary basement membrane, digitation of capillary endothelial cells, mitochondrial swelling, cristae disruption, and vacuolar degeneration in capillary endothelial cells, bipolar cells and ganglion cells, mitochondrial swelling and cristae disruption in pericytes, decreased membranous disc (photoreceptor cell’s outer segment), and widened gap between membranous discs. Conclusion The retina morphological changes of early stage background diabetic retinopathy(BDR) can be found in the 10th week after STZ injection in rats, and STZ-induced DR model can be used as an early stage DR model; besides, the method is simple, economical, quick, with good reproducibility and high successful rate. |
| Key words: diabetes mellitus retina animal model streptozotocin |
