内皮抑素通过增加细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达以及降低血管内皮生长因子（VEGF）的表达来抑制糖尿病大鼠的血视网膜屏障破坏。

Endostatin Inhibits Blood-Retinal Barrier Breakdown in Diabetic Rats by Increasing the Expression of ICAM-1 and VCAM-1 and Decreasing the Expression of VEGF.

作者信息

Zhou Jinhua, Xie Zhenggao

机构信息

Department of Ophthalmology, Yizheng Hospital, Nanjing Drum Tower Hospital Group, Yangzhou 211400, China.

Department of Ophthalmology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, China.

出版信息

Comput Math Methods Med. 2022 Jan 17;2022:5105866. doi: 10.1155/2022/5105866. eCollection 2022.

DOI:10.1155/2022/5105866

PMID:37795476

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10547573/

Abstract

OBJECTIVE

Endostatin has become the strongest endogenous angiogenesis inhibitor due to suppressing VEGF expression. The purpose of this study was to assess the impact of endostatin on the blood-retinal barrier (BRB) in diabetic rats.

METHODS

SD rats were induced to develop diabetes by streptozotocin, and endostatin was administrated by intravitreal injection. The body weight, the level of blood glucose, the expressions of C-reactive protein (CRP), adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), junction proteins (occludin, claudin-5, and zonula occluden-1), and VEGF were measured in rats' retinas of diabetes. The BRB breakdown was evaluated using Evans blue.

RESULTS

The level of CRP and adhesion molecules (ICAM-1 and VCAM-1) was increased in retinas of diabetic rats, while endostatin significantly inhibited the upregulation of these. Diabetes increased the BRB permeability and retinal thickness. Diabetes also decreased the levels of occludin, claudin-5, and ZO-1 in retinals. These changes were inhibited by endostatin treatment. Upregulation of vascular endothelial growth factor (VEGF), transforming growth factor- (TGF-), and protein kinase C- (PKC-) 2 was also reversed by endostatin in retinas of diabetic rats.

CONCLUSIONS

Endostatin provides protection against diabetic retinopathy, which may involve its barrier-enhancing effects.

摘要

目的

内皮抑素因抑制血管内皮生长因子（VEGF）表达而成为最强的内源性血管生成抑制剂。本研究旨在评估内皮抑素对糖尿病大鼠血视网膜屏障（BRB）的影响。

方法

用链脲佐菌素诱导SD大鼠患糖尿病，并通过玻璃体腔内注射给予内皮抑素。测量糖尿病大鼠视网膜的体重、血糖水平、C反应蛋白（CRP）、黏附分子细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）、连接蛋白（闭合蛋白、紧密连接蛋白-5和闭锁小带蛋白-1）以及VEGF的表达。用伊文思蓝评估血视网膜屏障的破坏情况。

结果

糖尿病大鼠视网膜中CRP和黏附分子（ICAM-1和VCAM-1）水平升高，而内皮抑素显著抑制了这些分子的上调。糖尿病增加了血视网膜屏障通透性和视网膜厚度。糖尿病还降低了视网膜中闭合蛋白、紧密连接蛋白-5和闭锁小带蛋白-1的水平。内皮抑素治疗可抑制这些变化。糖尿病大鼠视网膜中血管内皮生长因子（VEGF）、转化生长因子-β（TGF-β）和蛋白激酶C-δ（PKC-δ）2的上调也被内皮抑素逆转。