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capsazepine(CZP)是辣椒素的合成类似物,也是野香草型瞬时感受器电位通道1(TRPV1)的选择性抑制剂。TRPV1在体内有广泛的表达谱,使CZP有广泛的作用位点。除此之外,以往的研究结果表明CZP除了作用于TRPV1外还有更复杂的信号通路。本课题研究了CZP对体外培养的大鼠海马神经元网络内线粒体转运的作用并分析其可能机制。结果显示:20μmol/L的CZP可有效抑制原代培养海马神经元网络中的线粒体转运。CZP急性作用不引起胞内钙离子浓度的升高,也不引起细胞的调亡。胞外更换为无外钙记录液,或者将GSK3β抑制剂SB415286与CZP共孵育,均不影响CZP对线粒体转运的抑制作用。然而,将BAPTA-AM与CZP共孵育,抑制了CZP对线粒体转运的抑制作用。本研究结果表明,CZP直接通过胞内钙信号通路影响神经元的线粒体转运,与胞外钙流或转运蛋白的磷酸化无关。
Capsazepine (CZP), a synthetic analog of capsaicin, is also a selective inhibitor of wild vanilla type transient receptor potential channel 1 (TRPV1). TRPV1 has a wide range of expression profiles in vivo, allowing CZP to have a broad range of sites of action. In addition, previous studies have shown that CZP has more complex signaling pathways besides TRPV1. This study investigated the effect of CZP on mitochondrial transport in rat hippocampal neuronal cultures cultured in vitro and its possible mechanism. The results showed that 20μmol / L CZP could effectively inhibit the mitochondrial transport in primary cultured hippocampal neuronal networks. CZP does not cause acute effects of intracellular calcium concentration increased, nor caused apoptosis of cells. Extracellular exchange with no external calcium recording solution, or co-incubation of GSK3β inhibitor SB415286 with CZP did not affect the inhibitory effect of CZP on mitochondrial transport. However, co-incubation of BAPTA-AM with CZP inhibited the inhibitory effect of CZP on mitochondrial transport. The results of this study indicate that CZP directly affects the mitochondrial transport of neurons via the intracellular calcium signaling pathway and has nothing to do with the phosphorylation of extracellular calcium currents or transporters.