Guo Fan, Jiang Tao, Song Wenying, Wei Haidong, Wang Feng, Liu Lixin, Ma Lei, Yin Hong, Wang Qiang, Xiong Lize
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi Province, China.
Mol Neurobiol. 2015 Apr;51(2):685-95. doi: 10.1007/s12035-014-8765-y. Epub 2014 Jun 11.
Diabetes mellitus substantially increases the risk of stroke and enhances brain's vulnerability to ischemia insult. Electroacupuncture (EA) pretreatment was proved to induce cerebral ischemic tolerance in normal stroke models. Whether EA could attenuate cerebral ischemia injury in diabetic mice and the possible underlying mechanism are still unrevealed. Male C57BL/6 mice were subjected to streptozotocin (STZ) for diabetic models. After inducing focal cerebral ischemia model, the levels of plasma and cerebral adiponectin (APN) were measured as well as the expression of cerebral adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2). The neurobehavioral score, infarction volume, and cellular apoptosis were evaluated with or without AdipoR1 short interfering RNA (siRNA). The role of phosphorylation of glycogen synthesis kinase 3 beta (GSK-3β) at Ser-9 in the EA pretreatment was also assessed. EA pretreatment increased both plasma and cerebral APN levels and enhanced neuronal AdipoR1 in diabetic mice. In addition, EA reduced infarct size, improved neurological outcomes, and inhibited cell apoptosis after reperfusion. These beneficial effects were reversed by AdipoR1 knockdown. Furthermore, EA increased GSK-3β phosphorylation (p-GSK-3β) in the ipsilateral penumbra. Augmented p-GSK-3β induced neuroprotective effects similar to those of EA pretreatment. In contrast, dampened p-GSK-3β could reverse the neuroprotective effects of EA. In addition, the increase in p-GSK-3β by EA was abolished by AdipoR1 knockdown. We conclude that EA pretreatment increases the production of APN, which induce protective effects against cerebral ischemia-reperfusion injury through neuronal AdipoR1-mediated phosphorylation of GSK-3β in diabetic mice.
糖尿病显著增加中风风险，并增强大脑对缺血性损伤的易感性。电针（EA）预处理已被证明可在正常中风模型中诱导脑缺血耐受性。EA是否能减轻糖尿病小鼠的脑缺血损伤及其潜在机制仍未明确。将雄性C57BL/6小鼠用链脲佐菌素（STZ）诱导建立糖尿病模型。诱导局灶性脑缺血模型后，检测血浆和脑内脂联素（APN）水平以及脑内脂联素受体1（AdipoR1）和2（AdipoR2）的表达。使用或不使用AdipoR1小干扰RNA（siRNA）评估神经行为评分、梗死体积和细胞凋亡。还评估了EA预处理中糖原合成激酶3β（GSK-3β）在丝氨酸9位点的磷酸化作用。EA预处理可提高糖尿病小鼠的血浆和脑内APN水平，并增强神经元AdipoR1表达。此外，EA可减小梗死面积，改善神经功能结局，并抑制再灌注后的细胞凋亡。AdipoR1基因敲低可逆转这些有益作用。此外，EA可增加同侧半暗带中GSK-3β的磷酸化（p-GSK-3β）。增强的p-GSK-3β诱导的神经保护作用与EA预处理相似。相反，减弱的p-GSK-3β可逆转EA的神经保护作用。此外，AdipoR1基因敲低可消除EA引起的p-GSK-3β增加。我们得出结论，EA预处理可增加APN的产生，其通过神经元AdipoR1介导的GSK-3β磷酸化对糖尿病小鼠脑缺血再灌注损伤产生保护作用。
