Pioglitazone (PGZ), a PPARγ agonist, has been used for diabetic patients as an insulin-sensitizing agent. Recent studies have demonstrated that PGZ increases adiponectin (APN) levels and provides vascular protection in ischemic conditions. This study was designed to assess the neuroprotective effects of PGZ against cerebral ischemia–reperfusion injury via an APN-related mechanism. Type 2 diabetic leptin-deficient mice (db/db) were administered PGZ for 1 week, and plasma insulin and APN levels were measured. These mice received a middle cerebral artery occlusion and reperfusion injury, and they were evaluated for the infarct volume and by immunohistochemistry and western blotting analysis at several time points after ischemia. PGZ-administered db/db mice showed improved insulin sensitivity, and the hemorrhagic rate and infarct volume were decreased (P < 0.05). In the PGZ-administered group, plasma APN levels increased compared with the vehicle group. In the db/db group, PGZ administration significantly suppressed inflammatory reactions and oxidative stress after reperfusion (P < 0.05). PGZ may be applicable for acute cerebral ischemia treatment in metabolic syndrome patients as well as antidiabetic agents.

吡格列酮 (PGZ) 是一种 PPARγ 激动剂，已被用作糖尿病患者的胰岛素增敏剂。最近的研究表明，PGZ 会增加脂联素 (APN) 水平并在缺血条件下提供血管保护。本研究旨在通过 APN 相关机制评估 PGZ 对脑缺血再灌注损伤的神经保护作用。2 型糖尿病瘦素缺陷小鼠 ( db/db ) 给予 PGZ 1 周，并测量血浆胰岛素和 APN 水平。这些小鼠接受了大脑中动脉闭塞和再灌注损伤，并在缺血后的几个时间点对它们的梗塞体积进行了评估，并通过免疫组织化学和蛋白质印迹分析进行了评估。PGZ 管理的db/db小鼠胰岛素敏感性提高，出血率和梗死体积减少（P < 0.05）。在 PGZ 给药组中，与赋形剂组相比，血浆 APN 水平增加。在db/db组中，PGZ给药显着抑制再灌注后的炎症反应和氧化应激（P < 0.05）。PGZ可能适用于代谢综合征患者的急性脑缺血治疗以及降糖药。