Studies on leukocyte-endothelial interactions in the pathogenesis of diabetic retinopathy

糖尿病视网膜病变发病机制中白细胞-内皮相互作用的研究

• 批准号: 13470371
• 负责人: OGURA Yuichiro
• 金额: $ 8.77万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470371/
• 关键词: diabetic retinopathy; leukocyte-endothelial interaction; insulin; ICAM-1; acridine orange; gliclazide; pioglotazone hydrochloride; 白血球; インスリン; 網膜血管内皮細胞; 白血球-血管内皮相互作用; 網膜微小循環

Significance of interactions between leukocytes and retinal vascular endothelial cells in the pathogenesis of diabetic retinopathy was studied by both in vitro and in vivo. Human retinal endothelial cells (HREC) were cultured and the adhesion of neutrophils to the HREC was quantitated. Insulin significantly increased the adhesion of neutrophils to HREC in the dose dependent manner. ICAM-1 of HREC was upregulated by addition of insulin to the cultured medium. In vivo studies were carried out suing streptozotocin-induced diabetic rats. Acridine orange digital fluorography was performed to study leukocyte dynamics in the retinal microcirculation. Diabetic rats showed retinal leukostasis (accumulation of leukocytes in the retinal capillaries) as compared to the non-diabetic control animals. Gliclzide and pioglitazone hydrochloride effectively decreased the number of accumulated leukocyte in the retina of diabetic rats.

本研究从体外和体内两个方面探讨了白细胞与视网膜血管内皮细胞相互作用在糖尿病视网膜病变发病中的意义。培养人视网膜内皮细胞（HREC），并定量中性粒细胞对HREC的粘附。胰岛素以剂量依赖方式显著增加中性粒细胞与HREC的粘附。在培养液中加入胰岛素可上调HREC细胞ICAM-1的表达。使用链脲佐菌素诱导的糖尿病大鼠进行体内研究。进行吖啶橙子数字荧光造影以研究视网膜微循环中的白细胞动力学。与非糖尿病对照动物相比，糖尿病大鼠显示视网膜白细胞停滞（白细胞在视网膜毛细血管中积聚）。格列齐特和盐酸吡格列酮能有效降低糖尿病大鼠视网膜白细胞聚集。

项目成果

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Nishijima K：“抗凝血酶 III 对视网膜缺血再灌注损伤期间血细胞和内皮细胞之间相互作用的抑制作用。”Invest Ophasemol Vis Sci。

Nishiwaki A: "Upregulation of P-selectin and intercellular adhesion moeclule-1 after retinal ischemia-reperfusion injury"Invest Ophthalmol Vis Sci. 44. 4931-4935 (2003)

Nishiwaki A：“视网膜缺血再灌注损伤后 P-选择素和细胞间粘附分子 1 的上调”Invest Ophasemol Vis Sci。