Hyperglycemia is a well-known indicator of stroke prognosis, and one-third of nondiabetic patients develop postischemic hyperglycemia during the acute phase of stroke; this is related to relatively poor prognosis, high mortality, and impaired neurological recovery. Interleukin-13 (IL-13), a member of the Th2 cytokine family, is involved in both the regulation of immune response and glucose metabolism. Thus, we investigated the mechanism of postischemic hyperglycemia and the role of IL-13 by using a permanent middle cerebral artery occlusion (MCAO) rat model. Our results indicated that postischemic hyperglycemia was accompanied with hyperinsulinemia and increased HOMA-IR, elevated hepatic gluconeogenesis, and suppressed insulin signaling. A shift towards inflammatory response was evident with results of elevated proinflammatory cytokines and increased expression of negative regulatory proteins, suggesting an ongoing vicious cycle of inflammatory-induced insulin-resistant hyperglycemia. IL-13 treatment counteracted the proinflammatory states and abolished the vicious cycle through enhancing STAT6 and STAT3, which mediated the immune and metabolic pathways respectively; these effects resolved the formerly described pathological changes of postischemic hyperglycemia and reduced infarction size in the MCAO rats. Our findings demonstrated the importance of Th1-Th2 balance in the peripheral glucose metabolism affected by acute ischemic stroke, which provides a new perspective for the prevention and control of postischemic hyperglycemia.

高血糖是众所周知的中风预后指标，三分之一的非糖尿病患者在中风急性期出现缺血后高血糖。这与相对较差的预后、高死亡率和神经恢复受损有关。白细胞介素-13 (IL-13) 是 Th2 细胞因子家族的成员，参与免疫反应和葡萄糖代谢的调节。因此，我们通过使用永久性大脑中动脉闭塞（MCAO）大鼠模型研究了缺血后高血糖的机制和IL-13的作用。我们的结果表明，缺血后高血糖伴随着高胰岛素血症和 HOMA-IR 增加，肝糖异生增加，并抑制胰岛素信号传导。炎症反应的转变是明显的，促炎细胞因子升高和负调节蛋白表达增加，表明炎症诱导的胰岛素抵抗性高血糖存在持续的恶性循环。IL-13治疗通过增强分别介导免疫和代谢途径的STAT6和STAT3来抵消促炎状态并消除恶性循环；这些作用解决了先前描述的 MCAO 大鼠缺血后高血糖的病理变化并减少了梗塞面积。我们的研究结果证明了Th1-Th2平衡在急性缺血性脑卒中影响的外周葡萄糖代谢中的重要性，这为预防和控制缺血后高血糖提供了新的视角。