医学分子生物学杂志2026，Vol.23Issue(3)：294-301,8.DOI:10.3870/j.issn.1672-8009.2026.03.008
RAGE抑制剂TTP488降低糖尿病性视网膜病变小鼠模型中的视网膜炎症的疗效
Efficacy of RAGE Inhibitor TTP488 in Reducing Retinal Inflamma-tion in Diabetic Retinopathy Mice Model
摘要
Abstract
Objective To explore the efficacy and mechanisms of the receptor for advanced glycation end products inhibitor TTP488 in reducing retinal inflammation.Methods Thirty male C57BL/6J mice were randomly divided into 3 groups(n=10 each):control group,type I diabe-tes mellitus(T1DM)model group,and T1DM+TTP488 group.A T1DM mice model induced by streptozotocin(STZ)was established.Immunofluorescent staining targeting microglial cell markers(Iba1)was used to determine the activation degree of Iba1-positive cells in the retinal tissues of mice;and ELISA was used to measure the levels of inflammatory factors TNF-α,IL-1β and IL-6 in them.mRPE cells was divided into the following 5 groups for the further in vitro cell experiments:control group,LPS group,LPS+TTP488 group,LPS+shRNA-P65 group,LPS+shRNA-NT group.Lipopolysaccharide(LPS)was used to establish the primary mouse retinal pigment epithelial cells inflammatory model.Adenovirus vector was used to mediate the knockdown of P65.The expres-sion level of VEGF-D mRNA in cells was determined by RT-qPCR.The expression levels of phospho-rylated NF-κB P65(p-P65)/P65 and VEGF-D in the retinal tissues of mice as well as in in vitro cells were determined by Western blotting.Results Compared with those in the T1DM model group,the number of Iba1 positive cell branches and the number of Iba1 positive cell branch con-nection points(per field)in the T1DM+TTP488 group were decreased(P<0.05).The levels of TNF-α,IL-1β,and IL-6 were decreased(P<0.05).The relative expression levels of p-P65/P65 and VEGF-D were decreased(P<0.05).Compared with those in the LPS group,the relative ex-pression level of VEGF-D mRNA in the LPS+TTP488 group and the LPS+shRNA-P65 group was de-creased(P<0.05).The relative expression levels of p-P65 and VEGF-D were down-regulated(P<0.05).Conclusion TTP488 reduced the expression of VEGF-D by inhibiting the activation of NF-κB,thereby alleviating retinal inflammation and tissue structural abnormalities in the diabetic retinopathic mice model.关键词
糖尿病性视网膜病变/炎症/晚期糖基化终末产物/晚期糖基化终末产物受体/TTP488/血管内皮生长因子Key words
diabetic retinopathy/inflammation/advanced glycation end products/receptor for advanced glycation end products/TTP488/vascular endothelial growth factor分类
医药卫生引用本文复制引用
王岚,卢怡,邹云春..RAGE抑制剂TTP488降低糖尿病性视网膜病变小鼠模型中的视网膜炎症的疗效[J].医学分子生物学杂志,2026,23(3):294-301,8.基金项目
四川省基层卫生发展研究中心资助课题(No.SWFZ23-C-95) This work was supported by a grant from the Sichuan Provincial Center for Primary Health Care Development(No.SWFZ23-C-95). （No.SWFZ23-C-95）
