硫氢化钠对2型糖尿病小鼠模型视网膜病变的影响  

Effect of Sodium Hydrosulfide on Retinopathy in Type 2 Diabetes Mellitus Mice

作　　者：杨志凰 王利萍[1] 刘鹏飞 Yang Zhihuang;Wang Liping;Liu Pengfei(Department of Ophthalmology,Myopia Prevention and Control Center,Ineye Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610081,China;Department of Anatomy,School of Basic Medicine,Sanquan College of Xinxiang Medical University,Xinxiang 453000,China)

机构地区：[1]成都中医药大学银海眼科医院近视防控中心眼综合科,成都610081 [2]新乡医学院三全学院基础医学院解剖学教研室,新乡453000

出　　处：《成都医学院学报》2024年第6期943-948,共6页Journal of Chengdu Medical College

基　　金：四川省成都市金牛区医学科研课题(No:JNKY2024-98)。

摘　　要：目的探讨硫氢化钠(NaHS)对2型糖尿病小鼠视网膜病变(DR)的影响。方法将C57BL/6J雄性小鼠随机分为Sham组、T2DM组、T2DM+NaHS组,每组20只。Sham组采用常规饲料喂养,T2DM组构建2型糖尿病小鼠模型[使用高糖高脂饲料喂养8周,再腹腔注射链脲佐菌素(STZ)],T2DM+NaHS组在构建2型糖尿病小鼠模型后腹腔注射100μmol/kg NaHS,连续给药8周。蛋白酶消化实验比较3组视网膜血管损伤情况;HE染色比较3组视网膜血管增生情况;TUNEL染色比较3组凋亡阳性细胞数量;蛋白质印记法检测3组视网膜B淋巴细胞瘤-2(Bcl-2)、BCL2关联X蛋白(Bax)、白细胞介素18(IL-18)、白细胞介素1β(IL-1β)、血管内皮生长因子(VEGF)、缺氧诱导因子-1α(HIF-1α)的蛋白表达。结果与Sham组相比,T2DM组和T2DM+NaHS组视网膜血管周细胞迁移、新生血管平均数、TUNEL阳性细胞数及视网膜Bax/Bcl-2、IL-18、IL-1β、VEGF、HIF-1α的蛋白表达量明显增加(P<0.05),且T2DM组比T2DM+NaHS组增加更明显(P<0.05)。结论NaHS可抑制VEGF表达,降低2型糖尿病视网膜血管损伤、视网膜炎症和细胞凋亡。Objective To investigate the effect of sodium hydrosulfide(NaHS)on diabetic retinopathy(DR)in mice with type 2 diabetes mellitus(T2DM).Methods C57BL/6J male mice were randomly divided into a normal control Sham group,a T2DM model group,and a T2DM+NaHS treatment group,with 20 mice in each group.The Sham group was fed with conventional diet.Except the Sham group,the other two groups were fed with high sugar and high fat diet for 8 weeks,combined with intraperitoneal injection of streptozotocin(STZ),to construct mouse models of T2DM.And after modeling,the T2DM+NaHS group received intraperitoneal injection of 100 umol/kg NaHS for 8 consecutive weeks.Anesthetic enucleation was performed within 24 hours following the last administration.Protease digestion experiment was performed to observe the damage of retinal blood vessels.Hematoxylin and eosin(HE)staining was used to observe the retinal vascular proliferation.Comparision of the number of apoptotic positive cells in each group was made via terminal deoxyribonucleotidyl transferase(TDT)-mediated deoxyuridine triphosphate nick end labelling(TUNEL)staining.Immunoblotting was used to detect the expression levels of apoptosis related proteins:B-cell lymphoma-2(Bcl-2),BCL2 associated X protein(Bax),interleukin-18(IL-18),interleukin-1β(IL-1β),vascular endothelial growth factor(VEGF),and hypoxia inducible factor-1α(HIF-1α).Results Compared with the Sham group,the migration and loss of retinal perivascular cells,neovascularization,number of TUNEL positive cells,and protein expression levels of Bax/Bcl-2,IL-18,IL-1β,VEGF,and HIF-1αin the T2DM group and the T2DM+NaHS group were significantly increased(P<0.05),and the increase in the T2DM group was more significant than that in the T2DM+NaHS group(P<0.05).Conclusion NaHS can inhibit VEGF expression and reduce retinal vascular injury,retinal inflammation and apoptosis in mouse models of T2DM.

关 键 词：糖尿病视网膜病变 抗血管内皮生长素 硫氢化钠 2型糖尿病 

分 类 号：R774.1[医药卫生—眼科]