School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.
J Neuroinflammation. 2013 May 10;10:63. doi: 10.1186/1742-2094-10-63.
Emerging studies have demonstrated that pretreatment with electroacupuncture (EA) induces significant tolerance to focal cerebral ischemia. The present study seeks to determine the involvement of monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified novel modulator of inflammatory reactions, in the cerebral neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of EA pretreatment-induced ischemic brain tolerance.
Twenty-four hours after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 minutes in male C57BL/6 mice and MCPIP1 knockout mice. Transcription and expression of MCPIP1 gene was monitored by qRT-PCR, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, proinflammatory cytokines and leukocyte infiltration in brain and NF-κB signaling were evaluated after ischemia/reperfusion.
MCPIP1 protein and mRNA levels significantly increased specifically in mouse brain undergoing EA pretreatment. EA pretreatment significantly attenuated the infarct volume, neurological deficits, upregulation of proinflammatory cytokines and leukocyte infiltration in the brain of wild-type mice after MCAO compared with that of the non-EA group. MCPIP1-deficient mice failed to evoke EA pretreatment-induced tolerance compared with that of the control MCPIP1 knockout group without EA treatment. Furthermore, the activation of NF-κB signaling was significantly reduced in EA-pretreated wild-type mice after MCAO compared to that of the non-EA control group and MCPIP1-deficient mice failed to confer the EA pretreatment-induced inhibition of NF-κB signaling after MCAO.
Our data demonstrated that MCPIP1 deficiency caused significant lack of EA pretreatment-induced cerebral protective effects after MCAO compared with the control group and that MCPIP1 is involved in EA pretreatment-induced delayed brain ischemia tolerance.
新出现的研究表明，电针预处理可诱导局灶性脑缺血产生显著的耐受。本研究旨在确定单核细胞趋化蛋白诱导蛋白 1（MCPIP1）在电针预处理诱导的局灶性脑缺血动物模型中的脑保护作用中的作用，MCPIP1 是一种新发现的炎症反应调节因子，阐明电针预处理诱导的缺血性脑耐受的机制。
在雄性 C57BL/6 小鼠和 MCPIP1 敲除小鼠中，电针预处理结束后 24 小时，通过大脑中动脉闭塞（MCAO）诱导 90 分钟的局灶性脑缺血。通过 qRT-PCR、Western blot 和免疫组织化学监测 MCPIP1 基因的转录和表达。在缺血/再灌注后评估神经行为评分、梗死体积、促炎细胞因子和白细胞浸润以及 NF-κB 信号。
MCPIP1 蛋白和 mRNA 水平在经历电针预处理的小鼠大脑中特异性增加。与非电针组相比，电针预处理显著减轻了野生型小鼠 MCAO 后的梗死体积、神经功能缺损、脑内促炎细胞因子和白细胞浸润的上调。与未接受电针治疗的对照 MCPIP1 敲除组相比，MCPIP1 缺陷型小鼠未能引起电针预处理诱导的耐受。此外，与非电针对照组和 MCPIP1 缺陷型小鼠相比，MCAO 后电针预处理的野生型小鼠 NF-κB 信号的激活明显降低，MCPIP1 缺陷型小鼠未能引起电针预处理诱导的 NF-κB 信号抑制。
我们的数据表明，与对照组相比，MCPIP1 缺陷导致 MCAO 后电针预处理诱导的脑保护作用明显缺乏，并且 MCPIP1 参与电针预处理诱导的延迟性脑缺血耐受。
