We evaluated the effect of resveratrol (RSV) on graft survival after islet transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200 IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 μM) were incubated in a hypoxic chamber (O₂ 1%, 1hr). Some of the ITx was performed in mouse insulin 1 gene promoter-green fluorescent protein (MIP-GFP) transgenic mice and analyzed using an in vivo imaging system. After 14 days of ITx, 2-hr glucose levels on GTT in the RSV-treated group were significantly lower than those of other control groups. But the glucose status was not improved in No-ITx mice with RSV. At day 3, the percentage of Ki-67/insulin co-stained cells in islet graft was significantly increased in the RSV-ITx group. Immunostaining with anti-insulin and anti-BS-1 antibodies revealed significantly higher insulin-stained area and vascular density in RSV-treated islet grafts. The mean vessel volume per islet graft measured by in vivo imaging was significantly higher in the RSV-treated group at day 3. In isolated islets cultured in hypoxic conditions, the cell death rate and oxidative stress were significantly attenuated with RSV pretreatment. Hypoxic treatment for isolated islets decreased the expression of SIRT-1 mRNA, and this attenuation was recovered by RSV pretreatment. Our data suggest that RSV treatment improved glycemic control, beta-cell proliferation, reduced oxidative stress, and enhanced islet revascularization and the outcome of ITx in diabetic mice.

我们评估了白藜芦醇（RSV）对糖尿病小鼠胰岛移植（ITx）后移植物存活的影响。将来自Balb / c小鼠（200 IEQ）的分离的胰岛移植到糖尿病Balb / c小鼠的肾囊下。在ITx后14天给予媒介物或RSV（200 mg / kg /天，口服）。加入另外两个对照组[没有ITx的STZ治疗的（No-ITx-Control）和STZ + RSV治疗的（No-ITx-RSV）小鼠]。在ITx后14天进行葡萄糖耐量试验（GTT）。在体外，将用媒介物或RSV（1μM）预处理的分离的胰岛在缺氧室中孵育（O ₂ 1％，1hr）。某些ITx在小鼠胰岛素1基因启动子-绿色荧光蛋白（MIP-GFP）转基因小鼠中进行，并在体内进行了分析成像系统。ITx治疗14天后，RSV治疗组GTT的2小时葡萄糖水平明显低于其他对照组。但是在患有RSV的No-ITx小鼠中，葡萄糖状态并未改善。在第3天，RSV-ITx组中胰岛移植物中Ki-67 /胰岛素共染色细胞的百分比显着增加。用抗胰岛素和抗BS-1抗体进行的免疫染色显示，RSV处理的胰岛移植物中的胰岛素染色面积和血管密度明显更高。通过体内测量的每个胰岛移植物的平均血管体积在第3天，接受RSV治疗的组的影像学显着升高。在低氧条件下培养的离体胰岛中，RSV预处理显着减弱了细胞死亡率和氧化应激。对分离的胰岛进行低氧治疗会降低SIRT-1 mRNA的表达，这种衰减可以通过RSV预处理得到恢复。我们的数据表明，RSV治疗改善了糖尿病小鼠的血糖控制，β细胞增殖，降低了氧化应激，并增强了胰岛血运重建和ITx的结局。