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PG545 通过促进视网膜 Müller 细胞自噬来抑制炎症反应,从而缓解糖尿病视网膜病变。

PG545 alleviates diabetic retinopathy by promoting retinal Müller cell autophagy to inhibit the inflammatory response.

机构信息

Department of Ophthalmology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.

Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, China.

出版信息

Biochem Biophys Res Commun. 2020 Oct 22;531(4):452-458. doi: 10.1016/j.bbrc.2020.07.134. Epub 2020 Aug 13.

Abstract

Diabetic retinopathy (DR), a major cause of blindness in working-age people, is attributed to the inflammatory response of retinal Müller cells (RMCs). The heparanase inhibitor PG545 plays proautophagic and anti-inflammatory roles. Intraperitoneal injection of PG545 at a dose of 20 mg/kg/d clearly reduced diabetes-induced body weight changes and fasting blood glucose levels in mice. PG545 also mitigated the reduction in retinal thickness and the formation of microaneurysms by promoting autophagy to inhibit the inflammatory response. In vitro, PG545 stimulated autophagy to downregulate the inflammatory response in high glucose-induced primary adult mouse RMCs. These data suggest that PG545 mitigates DR by promoting RMC autophagy to inhibit the inflammatory response.

摘要

糖尿病性视网膜病变(DR)是导致工作年龄段人群失明的主要原因,其归因于视网膜 Müller 细胞(RMCs)的炎症反应。肝素酶抑制剂 PG545 具有促进自噬和抗炎作用。以 20mg/kg/d 的剂量腹腔注射 PG545 可明显减轻糖尿病诱导的小鼠体重变化和空腹血糖水平。PG545 通过促进自噬抑制炎症反应来减轻视网膜厚度的降低和微动脉瘤的形成。在体外,PG545 刺激自噬,下调高糖诱导的原代成年小鼠 RMCs 的炎症反应。这些数据表明,PG545 通过促进 RMC 自噬抑制炎症反应来减轻 DR。

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