二甲双胍对2型糖尿病大鼠视网膜的保护及其对血清胱抑素C的调节作用  

Protective effect of metformin on the retina of type 2 diabetic rats and its regulation on serum cystatin C

作　　者：白惠玲[1] 朱晓燕 刘勤[1,2] 张延英 康万荣 张书 Hui-Ling Bai;Xiao-Yan Zhu;Qin Liu;Yan-Ying Zhang;Wan-Rong Kang;Shu Zhang(Department of Ophthalmology,Gansu Provincial Hospital,Lanzhou 730000,Gansu Province,China;First School of Clinical Medical,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China;Research and Experiment Center,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China)

机构地区：[1]甘肃省人民医院眼科,甘肃省兰州市730000 [2]甘肃中医药大学第一临床医学院,甘肃省兰州市730000 [3]甘肃中医药大学科研实验中心,甘肃省兰州市730000

出　　处：《国际眼科杂志》2023年第1期23-31,共9页International Eye Science

基　　金：甘肃省卫生行业科研计划项目(No.GSWSKY-2019-40);兰州市科技计划项目(No.2020-ZD-18)。

摘　　要：目的:在大鼠2型糖尿病(T2DM)造模的基础上继续制备糖尿病视网膜病变(DR)模型,观察二甲双胍对T2DM大鼠DR的预防及保护作用和对血清胱抑素C(Cys C)的影响,并对其机制进行探讨。方法:筛选120只雄性SD大鼠,随机取30只分为空白对照组A(10只),T2DM组(10只)和二甲双胍干预组A(10只);其余90只随机分为三组,分别为空白对照组B(30只),DR组(30只)和二甲双胍干预组B(30只)。除空白对照组A、B外,其余所有组大鼠均构建T2DM模型,成模后二甲双胍干预组A大鼠给予二甲双胍灌胃,空白对照组A和T2DM组大鼠均给予生理盐水灌胃,干预3mo后分别测量三组大鼠的空腹血糖(FBG)和空腹血清胰岛素(FINS)指标,计算并分析胰岛素抵抗指数(HOMA-IR);测各组大鼠血清Cys C、肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、血管内皮生长因子(VEGF)和活性氧(ROS)水平,并行FFA、HE染色及透射电镜观察大鼠视网膜组织及血管形态;在T2DM病程3mo后,二甲双胍干预组B大鼠开始给予二甲双胍灌胃,其余大鼠均给予生理盐水灌胃,按干预时长不同,分别于第4、5、6mo各组取10只大鼠进行观察,测各组大鼠血清Cys C、TNF-α、IL-8、VEGF和ROS水平,并行FFA、HE染色及透射电镜观察大鼠视网膜组织及血管形态。结果:空白对照组A、T2DM组和二甲双胍干预组A三组间大鼠血清FBG、FINS、HOMA-IR、Cys C、TNF-α、IL-8、VEGF和ROS的表达均有差异(P<0.05),且均为T2DM组最高,二甲双胍干预组A低于T2DM组;空白对照组B、DR组和二甲双胍干预组B分别在4、5、6mo各同龄组中,三组间大鼠血清Cys C、TNF-α、IL-8、VEGF和ROS的表达均有差异(P<0.05),且均为DR组最高,二甲双胍干预组B的表达低于DR组,随着DR病程的延长,Cys C、TNF-α、IL-8、VEGF和ROS的表达也进一步增加;FFA结果显示:与对应的空白对照组相比,各模型组大鼠视网膜血管走行迂曲,并且随着病程的延长可见微动脉瘤及荧光渗�·AIM:To prepare the model of diabetic retinopathy(DR)on the basis of the model of type 2 diabetes mellitus(T2 DM)in rats,observe the preventive and protective effect of metformin on DR in T2 DM rats and the effect on serum Cystatin C(Cys C),and discuss its mechanism.·METHODS:A total of 120 male SD rats were selected and 30 rats were randomly divided into blank control group A(10 rats),T2 DM group(10 rats)and metformin intervention group A(10 rats).The remaining 90 rats were randomly divided into three groups:blank control group B(30 rats),DR group(30 rats)and metformin intervention group B(30 rats).Except for blank control groups A and B,T2 DM models were constructed in all other groups.After modeling,rats in metformin intervention group A were given metformin by gavage,and rats in blank control group A and T2 DM group were given normal saline by gavage.After 3 mo of intervention,fasting blood glucose(FBG)and fasting serum insulin(FINS)indexes of the three groups were measured respectively,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated and analyzed;The serum Cys C,tumor necrosis factor-α(TNF-α),the levels of Interleukin-8(IL-8),vascular endothelial growth factor(VEGF)and reactive oxygen species(ROS)were measured,and we observed the retinal tissue and vascular morphology of rats by FFA,HE staining and transmission electron microscopy;rats in metformin intervention group B began to give metformin by gavage 3 mo after the course of T2 DM,and other rats were given normal saline.According to the length of intervention,10 rats were taken from each group and observed at 4,5 and 6 mo respectively.Serum levels of Cys C,TNF-α,IL-8,VEGF and ROS were measured in each group.We observed the retinal tissue and vascular morphology of rats by FFA,HE staining and transmission electron microscopy.·RESULTS:The expressions of serum FBG,FINS,HOMA-IR,Cys C,TNF-α,IL-8,VEGF and ROS were statistically significant among the blank control group A,T2 DM group and metformin intervention group A(P<0.05

关 键 词：二甲双胍 2型糖尿病 糖尿病视网膜病变 血清胱抑素C 

分 类 号：R587.2[医药卫生—内分泌] R774.1[医药卫生—内科学]