不同种属大鼠糖尿病视网膜病变模型比较研究  

Comparison on Diabetic Retinopathy Models Established with Different Lines of Rats

作　　者：左祥铎 梅敉佳 刘晓兰 徐翔 段俊华 李学芳 邱斌 李静平 ZUO Xiangduo;MEI Mijia;LIU Xiaolan;XU Xiang;DUAN Junhua;LI Xuefang;QIU Bin;LI Jingping(College of Traditional Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500)

机构地区：[1]云南中医药大学中药学院,昆明650500

出　　处：《中药药理与临床》2025年第2期80-84,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金委员会地区科学基金项目(编号:82260795);云南省中医药基础研究联合专项重点项目(编号:202301AZ070001-001);云南省中青年学术和技术带头人后备人才项目(编号:202405AC350030);云南省重大专项项目(编号:202102AA310045);云南中医药大学“培土生金”培育学科。

摘　　要：目的:探究链脲佐菌素(STZ)诱导的两个种属大鼠糖尿病视网膜病变(DR)模型之间的差异。方法:健康成年雄性SPF级SD和BN大鼠,采用小剂量多次腹腔注射STZ诱发糖尿病模型,另设SD和BN正常对照组,10只/组。观察各组动物一般状态变化;每周测血糖、体质量等生理指标;4、8、12 w进行光学相干断层扫描技术(OCT)及荧光素钠血管造影(FFA)检测;HE染色检查大鼠视网膜组织病理变化。结果:相较SD大鼠,BN大鼠成模率高,死亡率低。随着病程的进展,两种属大鼠与正常对照组比较,模型对照组血糖明显升高、体质量降低;FFA结果显示,BN大鼠视网膜出现明显荧光素钠渗漏现象;OCT结果显示,BN大鼠模型对照组视网膜厚度增长缓慢,这与HE结果相应,且HE结果可知两种属大鼠模型对照组神经节细胞(RGCs)减少,视网膜各层细胞均出现不同程度损伤且排列紊乱,视网膜整体厚度逐渐变薄。结论:STZ诱导的DR模型,BN大鼠较SD大鼠模型成模率高、死亡率低;由于BN大鼠视网膜特有色素层,则OCT和FFA检测成像及HE切片效果均明显优于SD大鼠,其在病理变化方面与人类DR具有相同或相似的特征,更适宜用做DR发病和药物作用机制研究的动物模型。Objective:To compare the diabetic retinopathy(DR)models established with streptozotocin(STZ)in two rat lines.Methods:Healthy adult male specific pathogen-free(SPF)-grade Sprague-Dawley(SD)and Brown Norway(BN)rats were injected intraperitoneally with a small dose of STZ to induce diabetes mellitus,and control groups of SD and BN were set up,with 10 rats per group.The general state of the rats in each group was observed throughout the experiment,and physiological indexes such as blood glucose and body mass were measured weekly.Optical coherence tomography(OCT)and fundus fluorescein angiography(FFA)were performed at the time points of 4,8,and 12 weeks,and hematoxylin-eosin(HE)staining was employed to examine the histopathological changes in the retina.Results:BN rats had high-er success rate and lower mortality rate than SD rats in the modeling.As the disease progressed,the model groups showed elevated blood glu-cose levels and decreased body mass compared with the control group.FFA results showed that sodium fluorescein leakage occurred in the ret-inae of BN rats.OCT results showed that the retinal thickness of the BN model group increased slowly.This result corresponded to that of HE staining,which showed a decrease in the number of retinal ganglion cells(RGCs),damaged and disarranged cells in different layers of the ret-ina,and gradual thinning of the retina in the two model groups.Conclusion:In the modeling of DR with STZ,BN rats had higher success rate and lower mortality rate than SD rats.Because of the unique pigment layer in the retinae,BN rats outperformed SD rats in terms of OCT and FFA imaging as well as HE staining results.The pathological changes of BN rats had the same or similar characteristics with those of humans,which made BN rats more suitable to be used for modeling in the research on the pathogenesis of DR and the mechanism of drug action.

关 键 词：大鼠糖尿病视网膜病变模型 斯泼累格·多雷大鼠 棕色挪威大鼠 

分 类 号：R-332[医药卫生]