The chronic protective effects of limb remote preconditioning and the underlying mechanisms involved in inflammatory factors in rat stroke.
The chronic protective effects of limb remote preconditioning and the underlying mechanisms involved in inflammatory factors in rat stroke.
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DOI：
10.1371/journal.pone.0030892
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Wei D;Ren C;Chen X;Zhao H
我们最近证明肢体远端预处理（LRP）可预防卒中后2天测量的局灶性缺血。在这里，我们研究了LRP是否提供长期保护并改善神经功能。我们还研究了LRP是否通过传入神经通路从预处理肢体传递其保护性信号到缺血性脑，以及炎症因子是否参与LRP，包括新的半乳糖凝集素-9/Tim-3炎症细胞信号通路，其诱导淋巴细胞死亡。在卒中前即刻在左后股动脉中进行LRP。LRP在中风后2天和60天都减少了脑损伤的大小，并改善了长达2个月的行为结果。感觉神经抑制剂辣椒素和神经节阻滞剂六甲铵可消除LRP的保护作用。此外，LRP抑制水肿形成和血脑屏障（BBB）的渗透性中风后2天测量。免疫印迹和免疫染色分析表明，LRP抑制半乳糖凝集素-9和T细胞免疫球蛋白结构域和粘蛋白结构域3（Tim-3）的蛋白表达，这是中风后增加。此外，LRP降低脑卒中后iNOS和硝基酪氨酸蛋白的表达。总之，LRP对中风具有长期保护作用，并可能通过抑制半乳糖凝集素-9/Tim-3通路、iNOS和硝基酪氨酸的活性来阻断脑损伤。
We recently demonstrated that limb remote preconditioning (LRP) protects against focal ischemia measured 2 days post-stroke. Here, we studied whether LRP provides long-term protection and improves neurological function. We also investigated whether LRP transmits its protective signaling via the afferent nerve pathways from the preconditioned limb to the ischemic brain and whether inflammatory factors are involved in LRP, including the novel galectin-9/Tim-3 inflammatory cell signaling pathway, which induces cell death in lymphocytes. LRP in the left hind femoral artery was performed immediately before stroke. LRP reduced brain injury size both at 2 days and 60 days post-stroke and improved behavioral outcomes for up to 2 months. The sensory nerve inhibitors capsaicin and hexamethonium, a ganglion blocker, abolished the protective effects of LRP. In addition, LRP inhibited edema formation and blood-brain barrier (BBB) permeability measured 2 days post-stroke. Western blot and immunostaining analysis showed that LRP inhibited protein expression of both galectin-9 and T-cell immunoglobulin domain and mucin domain 3 (Tim-3), which were increased after stroke. In addition, LRP decreased iNOS and nitrotyrosine protein expression after stroke. In conclusion, LRP executes long-term protective effects against stroke and may block brain injury by inhibiting activities of the galectin-9/Tim-3 pathway, iNOS, and nitrotyrosine.