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本研究旨在探讨激活MrgC受体(Mas-related gene C receptors)调制吗啡耐受的细胞学机制。对大鼠连续6天鞘内注射10μL生理盐水、吗啡(20μg)、吗啡+牛肾上腺髓质8-22(bovine adrenal medulla 8-22,BAM8-22,1 nmol,隔天注射)或(Tyr6)-2-MSH-6-12(MSH,5 nmol,隔天注射);用Western blot、免疫组织化学和实时荧光定量PCR的方法检测脊髓和背根神经节(dorsal root ganglion,DRG)中与吗啡耐受相关分子的表达。结果显示:鞘内给予选择性MrgC受体激动剂BAM8-22或MSH,能抑制慢性应用吗啡所诱发的脊髓背角和/或DRG中谷氨酸转运体(GLAST、GLT-1、EAAC1)的减少和神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)的增加。此外,检测到MrgC受体样免疫活性表达于脊髓背角浅层;慢性应用吗啡使脊髓背角MrgC受体样免疫活性和DRG中MrgC受体mRNA水平都增加。这些结果提示,MrgC受体通过抑制慢性应用吗啡所诱发的脊髓和DRG中的痛介质增加,而抑制吗啡耐受。
The purpose of this study was to investigate the cytological mechanisms that activated Masg-related gene C receptors modulate morphine tolerance. Rats were injected intrathecally with 10 μL of normal saline, morphine (20 μg), morphine + bovine adrenal medulla 8-22 (BAM8-22, 1 nmol, injections) or (Tyr6) 2-MSH-6-12 (MSH, 5 nmol) was injected into the spinal cord and dorsal root ganglion (DRG) by Western blot, immunohistochemistry and real-time fluorescence quantitative PCR. Tolerance to the expression of related molecules. The results showed that intrathecal administration of the selective MrgC receptor agonist BAM8-22 or MSH inhibited the reduction of glutamate transporters (GLAST, GLT-1, EAAC1) in spinal dorsal horn and / or DRG induced by chronic morphine administration And neuronal nitric oxide synthase (nNOS) increase. In addition, MrgC receptor-like immunoreactivity was detected in the superficial layer of spinal dorsal horn. Chronic application of morphine increased both MrgC receptor-like immunoreactivity in spinal dorsal horn and MrgC receptor mRNA in DRG. These results suggest that MrgC receptor inhibits morphine tolerance by inhibiting the increase of pain mediators in spinal cord and DRG induced by chronic morphine administration.