IOVS：糖尿病药二甲双胍或可防治葡萄膜炎

5月7日，美国研究人员在美国《调查性眼科与视觉科学》（Investigative Ophthalmology & Visual Science）月刊上报告说，他们完成的动物研究显示，常用糖尿病药物二甲双胍可以预防并治疗常见的致盲疾病——葡萄膜炎。

得克萨斯大学研究人员给患有葡萄膜炎的小鼠喂食二甲双胍，小鼠炎症显著减轻；而在小鼠患病前喂食二甲双胍，则可起到预防作用。研究人员发现，二甲双胍的作用机制在于它能激活一种名为AMPK的酶，后者可抑制细胞核因子酉乙蛋白的活性，使维持葡萄膜炎所需的细胞活素、趋化因子两类炎症信号分子难以生成。

研究人员说，由于二甲双胍在临床上已被广泛应用，安全性已得到证实，它有可能很快被批准用于治疗葡萄膜炎。

葡萄膜炎指虹膜、睫状体、脉络膜的炎症，是一种多发于青壮年的眼病，病因复杂，在致盲眼病中占有重要地位。由于其发病机制尚不完全清楚，故其预防无从着手，治疗效果也很不理想。目前，美国失明者中，10%到15%由葡萄膜炎所致，在世界范围内，这一比例更高。

拓展阅读：

替米沙坦与二甲双胍联合降压可改善糖脂代谢

荟萃分析：二甲双胍治疗糖尿病的风险和效益

Cancer Pre Res：药物二甲双胍或有助预防原发性肝癌

Diabetes Care：长期应用二甲双胍可预防大鼠慢性心衰发生

二甲双胍可降低原发性肝细胞癌的发病率

二甲双胍通过miRNA抑制胰腺癌干细胞，治疗胰腺癌

AJG：女性服二甲双胍或可预防胰腺癌

二甲双胍降低癌症发病率秘密被揭开

doi:10.1167/iovs.12-9432
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Anti-Diabetic Drug Metformin Suppresses Endotoxin-induced uveitis in Rats.

Nilesh M. Kalariya1, Mohammad Shoeb2, Naseem H. Ansari3, Satish K. Srivastava4 and Kota V. Ramana5,*

Purpose. To investigate the therapeutic effects of metformin, a commonly used anti-diabetic drug, in preventing endotoxin-induced uveitis (EIU) in rats. Methods. EIU in Lewis rats was developed by subcutaneous injection of lipopolysaccharide (LPS; 150ug). Metformin (300 mg/kg body wt, i.p) or its carrier was injected either 12 h prior to or 2 h post LPS induction. Three and 24 h after EIU, eyes were enucleated and aqueous humor (AqH) was collected. The MILLIPLEX-MAG Rat cytokine-chemokine magnetic bead array was used to determine inflammatory cytokines. The expression of Cox-2, phosphorylation of AMPK and NF- B (p65) were determined immunohistochemically. Primary human non-pigmented ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of metformin. Results. Compared to controls, the EIU rat AqH had significantly increased number of infiltrating cells and increased levels of various cytokines and chemokines (TNF-α , MCP-1, IL-1β, MIP-1α, IL-6, Leptin, and IL-18) and metformin significantly prevented the increase. Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues. Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media. Conclusions. Our results for the first time demonstrate a novel role of anti-diabetic drug, metformin, in suppressing uveitis in rats and suggest that this drug could be developed to prevent uveitis complications.