神经病理性疼痛增强HCN2通道在大鼠触液核的表达

发布时间：2019-05-16 00:52

【摘要】：本文旨在研究超极化激活环核苷酸门控通道亚型2(hyperpolarization-activated cyclic nucleotide-gated channels subtype2,HCN2)在触液核的分布及其在神经病理性疼痛条件下的表达变化,以期为揭示触液核的生物学功能及神经病理性疼痛的调控机制提供实验依据。以Sprague-Dawley(SD)大鼠为实验动物,用坐骨神经慢性压迫损伤(chronic constriction injury,CCI)法制作神经病理性疼痛模型,用侧脑室注射辣根过氧化物酶标记的霍乱毒素B亚单位复合物(CB-HRP)特异性标记触液核神经元,用热缩足潜伏期及机械缩足阈值作为定量指标研究痛行为,用免疫荧光法及Western blot检测触液核HCN2通道蛋白及c-Fos蛋白的表达量。结果显示,与正常大鼠相比,接受侧脑室CB-HRP注射的大鼠痛阈及触液核HCN2、c-Fos表达均无明显变化;而CCI术后第7、14天,神经病理性疼痛模型大鼠痛阈显著下降,且触液核神经元的HCN2通道蛋白及c-Fos蛋白的表达显著增加。使用HCN2阻断剂ZD7288后,CCI致痛大鼠痛阈显著提高,触液核神经元HCN2通道蛋白及c-Fos蛋白的表达较相应时间点模型组显著降低,以术后第7、14天为明显。以上结果提示,触液核可能参与了神经病理性疼痛的调制,且通过HCN2通道发挥重要作用。
[Abstract]:The purpose of this study was to study the distribution of hyperpolarized activated cyclic nucleotidyl gated channel subgroup 2 (hyperpolarization-activated cyclic nucleotide-gated channels subtype2,HCN2) in the contact nucleus and its expression in neuropathic pain. In order to provide experimental basis for revealing the biological function of contact nucleus and the regulation mechanism of neuropathic pain. Using Sprague-Dawley (SD) rats as experimental animals, the neuropathic pain model was established by chronic compression injury of sciatic nerve (chronic constriction injury,CCI). The neurons in the contact nucleus were specifically labeled with horseradish peroxisome labeled cholera toxin B subunit complex (CB-HRP). The latent period of thermal foot contraction and the threshold of mechanical foot contraction were used as quantitative indexes to study the pain behavior. The expression of HCN2 channel protein and c-Fos protein in contact nucleus was detected by immunofluorescence and Western blot. The results showed that compared with normal rats, there were no significant changes in pain threshold and HCN2,c-Fos expression in contact nucleus of rats injected with CB-HRP into lateral ventricle. On the 7th and 14th day after CCI, the pain threshold of neuropathic pain model rats decreased significantly, and the expression of HCN2 channel protein and c-Fos protein in fluid-contact nucleus neurons increased significantly. After using HCN2 blocker ZD7288, the pain threshold of CCI induced pain rats was significantly increased, and the expression of HCN2 channel protein and c-Fos protein in contact nucleus neurons was significantly lower than that in the model group at the corresponding time point, especially on the 7th and 14th day after operation. These results suggest that the contact nucleus may be involved in the modulation of neuropathic pain and play an important role through the HCN2 channel.
【作者单位】：徐州医学院江苏省麻醉学重点实验室;
【基金】：supported by the National Natural Science Foundation of China(No.81371243) Natural Science Foundation of Jiangsu Province,China(No.BK2012580)
【分类号】：R338

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