【作者】 曾雪爱；

【导师】 林跃鑫； 洪炎国；

【作者基本信息】 福建师范大学 ， 生物化学与分子生物学， 2005， 硕士

【摘要】 BAM22(bovine adrenal medulla peptide 22)是前脑啡肽A(内源性Met-和Leu-脑啡肽的前体)的一种水解产物,它含有22个氨基酸。BAM22被发现存在于中枢神经系统中,如大脑皮层、尾状核、海马、下丘脑、中脑导水管灰质、中脑和脊髓背角,但其功能还不清楚。BAM22具有阿片的作用,它与μ、δ和κ阿片受体都具很高的亲和力。此外,还能与一种新受体结合,这种受体的mRNA只独特地存在于管躯干四肢感觉的脊根神经节(dorsal horn ganglia,DRG)和管头面部感觉的三叉神经节的小细胞神经元里,因此,被命名为感觉神经元特异性受体(sensoryneuron-specific receptor,SNSR)。从目前的研究看来,BAM22可能是SNSR受体的内源性配基,所以对BAM22的研究不仅有助于弄清其功能作用,而且也有助于揭示SNSR受体的特性。BAM8-22是SNSR受体选择性的激动剂,它对阿片受体无亲和性,本实验分别采用行为学和免疫组织化学的方法,从整体水平和细胞水平研究了BAM22和BAM8-22对大鼠伤害性反应的作用。 实验结果显示椎管内注射BAM22减小大鼠在福尔马林痛反应和热刺激甩尾反应中的疼痛行为。而且这个结果与脊髓背角Ⅰ-Ⅱ、Ⅲ-Ⅳ、Ⅴ-Ⅵ层c-Fos蛋白的表达下降一致。腹腔注射阿片受体的拮抗剂纳洛酮(1-10mg/kg)只能部分阻断BAM22的作用。实验结果还显示椎管内注射BAM8-22也抑制大鼠福尔马林反应中的疼痛行为。 这些结果表明BAM22在脊髓水平通过阿片和非阿片的机制参与疼痛调制作用,此实验首次阐明了SNSR参与了疼痛的调制。更多还原

【Abstract】 Bovine adrenal medulla 22 (BAM22), a cleaved product of proenkepha-lin A, is found in the central nervous system including the cerebral cortex, caudate putamen, hippocampus, hypothalamus, periaqueductal gray, midbrain and spinal cord. BAM22 binds to μ-, δ- and K-opioid receptors with a high affinity and also potently activates the sensory neuron-specific receptor (SNSR), a novel receptor that is uniquely distributed in small-diameter neurons in the dorsal root ganglia (DRG) and trigeminal ganglia. The fact that BAM22 seems to be only endogenous ligand that activates SNSR makes it very interesting and important to investigate BAM22. The present study examined the effects of BAM22 and BAM8-22 on nociceptive responses in naive animals and the animals with injury at the systemic and cellular levels using behavioral assays and immunocytochemistry.The study demonstrated that intrathecal (i.t.) BAM22 decreased nocifensive behavior in the first and second phases of the formalin test, and increased the tail-withdrawal (TW) latency. Furthermore, these results were associated with decreases of formalin-induced expressions of c-fos-like immunoreactivity in laminae I-II, HI-IV and V-VI of the spinal cord. The BAM22-induced behavior and neuronal responses were significantly attenuated, but not completely abolished by intraperitoneal (i.p.) the opioid receptor antagonist naloxone at maximally effective doses (1-10 mg/kg). The study also demonstrated that intrathecal BAM8-22 inhibited nocifensive behavior in the second phase of the formalin test.These results indicate that BAM22 suppresses nociceptive processing at the spinal level via opioid and non-opioid mechanisms. This is the first study to demonstrate that SNSR is involved in pain modulation.更多还原