Inhibitory effect of an angiotensin II receptor antagonist in diabetic retinopathy

血管紧张素II受体拮抗剂对糖尿病视网膜病变的抑制作用

• 批准号: 14571652
• 负责人: YOSHIDA Akitoshi
• 金额: $ 2.24万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571652/
• 关键词: Diabetes; losrtan; AT II receptor antagonist; SLO; OCT; Choroidal circulation

Background : The effectiveness of losartan for the treatment of leukocyte entrapment in the retinal microcirculation of diabetic rats was evaluated quantitatively.Methods : After diabetes was induced by injection of streptozotocin(STZ), the rats were divided into two subgroups. The first subgroup(n=6), received no medications ; the second subgroup(n=6) was given fresh drinking water supplemented with losartan(5mg/kg/day) for 4 weeks. Six rats that were not injected with STZ or given medications served as controls. 4 weeks after intervention leukocyte dynamics in the retina were observed using acridme orange digital fluorography. Leukocyte entrapment in the retina was compared among the three groups.Results : In the untreated diabetic rats, the number of trapped leukocytes(6.1(SD1.4)cells/mm2) increased significantly compared with control rats(2.8(1.2) cells/mm2;p=0.005) and diabetic rats treated with losartan(3.1(0.9)cells/mm2;p=0.0002).Conclusions : Losartan, an AT1 angiotensin II receptor antagonist, inhibited increased leukocyte entrapment in the diabetic retina. The authors demonstrated that losartan may have therapeutic efficacy in preventing development of diabetic retinopathy. Futher clinical studies of the effect of the angiotensin receptor antagonist on preventin development of diabetic retinopathy are needed.

背景资料：方法：采用链脲佐菌素（STZ）诱导糖尿病大鼠模型，随机分为两组，每组10只。第一组（n=6）不接受任何药物治疗;第二组（n=6）给予新鲜饮用水补充氯沙坦（5 mg/kg/d）4周。6只未注射STZ或给予药物的大鼠作为对照。干预4周后，用吖啶橙子数字荧光成像观察视网膜中白细胞动态。结果：糖尿病组视网膜白细胞滞留数明显低于对照组，视网膜白细胞滞留数明显低于正常对照组，视网膜白细胞滞留数明显低于正常对照组。（6.1（SD1.4）个细胞/mm 2）与对照组相比显著增加（2.8（1.2）个细胞/mm 2;p=0.005）和氯沙坦治疗的糖尿病大鼠结论：血管紧张素Ⅱ受体拮抗剂氯沙坦可抑制糖尿病视网膜白细胞滞留。作者证明，氯沙坦可能在预防糖尿病视网膜病变的发展方面具有治疗效果。血管紧张素受体拮抗剂在预防糖尿病视网膜病变发展中的作用还需要进一步的临床研究。

项目成果

Fumihiko Mori, et al.: "Pulsatile Ocular Blood Flow is Unaffected in Type 2 Diabetes Mellitus"Japanese Journal of Ophthalmology. 47. 621-622 (2003)

Fumihiko Mori 等人：“脉动眼部血流在 2 型糖尿病中不受影响”，日本眼科杂志。

Fumihiko Mori, et al.: "Inhibitory effect of losartan, an AT1 II receptor antagonist, on increased leukocyte entrapment in retinal microcirculation of diabetic rats."British Journal of Ophthalmolgy. 86. 1172-1174 (2002)

Fumihiko Mori 等人：“氯沙坦（一种 AT1 II 受体拮抗剂）对糖尿病大鼠视网膜微循环中白细胞滞留增加的抑制作用。”英国眼科杂志。

Fumihiko Mori, et al.: "Dysfunction of active transport of blood retinal barrier in patients with clinically significant macular edema in type 2 diabetes."Diabetes Care. 25(7). 1248-1249 (2002)

Fumihiko Mori 等人：“2 型糖尿病临床显着黄斑水肿患者的血视网膜屏障主动运输功能障碍。”糖尿病护理。

Taiji Nagaoka, et al.: "Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes."British Journal of Ophthalmology. (in press).

Taiji Nagaoka 等人：“2 型糖尿病患者中心凹区域脉络膜循环的改变。”英国眼科杂志。

Mori F, et al.: "Inhibitory effect of losartan, an AT II receptor antagonist, on increased leukocyte entrapment in retinal microcirculation of diabetic rats"Br J Ophthalmol. 86. 1172-1174 (2002)

Mori F 等人：“氯沙坦（一种 AT II 受体拮抗剂）对糖尿病大鼠视网膜微循环中白细胞滞留增加的抑制作用”Br J Ophamol。