趋化因子MCP-1对辣椒素受体(TRPV1)功能的易化作用与其机制分析.pdfVIP

趋化因子 MCP-1 对辣椒素受体(TRPV1)功能的易化作用及其机制研究 Abstract MCP-1 (monocyte chemoattractant protein-1) is one of the CC chemokine subfamily members. The expression of MCP-1 was increased in neurons and glial cells after the nerve injuries ，inflammation or other pathological changes. MCP-1 can directly enhance the excitability of neurons.As a new member of the family ，MCP-1-1 is considered to be an important new mediator that produces pain. TRPV1 is an thermal non-selective cation channel which mainly expresses in small or medium neurons and unmyelinated C fibers or Aδ nerve fibers of the dorsal root ganglia, trigeminal ganglia. The accumulated evidences demonstrate that TRPV1 is a very important pain mediators mediating pain sensitivity. The purpose of this research is to investigate the modulation of TRPV1 by MCP-1 in an animal pain model of the chronically compressed dorsal root ganglia (CCD). The main results are as follows: 1 As assessed by Real-time PCR, the mRNA expression of TRPV1 was increased in CCD-injured dorsal root ganglia (DRG). The co-expression of CCR2, the cognate receptor for MCP-1 TRPV1 was found DRG neurons in the DRG tissue slices by immunofluorescence method. 2. Spontaneous pain behavior test showed that MCP-1 enhanced capsaicin-induced flinching. The paw lifting time per minute (PLTPM) in CCD rats received a con-injection of MCP-1 with capsaicin is significantly higher than that received a single injection of capsaicin. 3. The whole-cell patch-clamp recordings demonstrated the enhancement by MCP-1 of membrane depolarization and inward current amplitude induced by capsaicin in acutely isolated CCD neurons. Also, the free intracellular calcium that entry through