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作 者:魏义明[1,2] 许盈[1] 俞昌喜[1] 韩静[1]
机构地区:[1]福建医科大学药学院药理学系 [2]基础医学院生理与病理生理学系,福州350004
出 处:《生理学报》2009年第3期255-262,共8页Acta Physiologica Sinica
基 金:supported by the Project for the Plan of Science and Technology Exploitation of Fujian Province, China (No. 2005D073);the Natural Science Foundation of Fujian Province, China (No. C0410018);the Project of Science and Technology Bureau of Fujian Province, China (No. 2006F5046)
摘 要:本文旨在考察褪黑素(melatonin,MEL)对吗啡依赖形成的作用。昆明小鼠皮下注射吗啡的同时腹腔注射MEL,连续8天,形成吗啡依赖,第8天最后一次吗啡注射后2h,皮下注射纳洛酮催促戒断。采用免疫组织化学和RT-PCR法,结合计算机图像处理技术,测定MEL对吗啡依赖小鼠下丘脑弓状核(hypothalamic arcuate nucleus,ARH)中β-内啡肽(β-endorphin,β-EP)表达的影响。结果显示,连续8d给予MEL(20mg/kg),在显著抑制吗啡依赖小鼠纳洛酮催促戒断症状的同时(P<0.05),可显著增强ARH中β-EP样免疫阳性反应强度及β-EP前体物阿黑皮素原(proopiomelanocortin,POMC)mRNA的表达(P<0.05)。上述结果提示,MEL可促进ARH中β-EP的生成,这可能是其抑制小鼠吗啡依赖性形成的机制之一。The study was conducted to investigate the effect of melatonin (MEL) on the expression of β-endorphin (β-EP) in the hypothalamic arcuate nucleus (ARH) of morphine-dependent mice. For a period of 8 consecutive days, male Kunming strain mice were injected subcutaneously (s.c.) with normal saline or increasing doses (10-80 mg/kg) of morphine, and intraperitoneally (i.p.) with MEL (10, 20 or 40 mg/kg) or vehicle (5 % ethanol saline) simultaneously. Withdrawal response was induced by naloxone (3 mg/kg, s.c.) at 2 h after final morphine injection on the 8th day. The potency of withdrawal response was evaluated according to the jumping times and the body weight loss. After that, the expressions of β-EP and proopiomelanocortin (POMC) mRNA in ARH were examined by immunohistochemistry and RT-PCR, respectively. The results showed that MEL (i.p., 20 mg/kg) decreased the naloxone-precipitated withdrawal responses in morphine-dependent mice significantly (P〈0.05). Meanwhile, MEL increased the intensity of β-EP-like immunoreactivity and enhanced the expression of POMC mRNA in ARH (P〈0.05). These results suggest that MEL increases the expression of β-EP in ARH of morphine-dependent mice, which may partly contribute to the action of MEL to inhibit the development of morphine dependence.
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