吗啡对雌性大鼠性腺轴和骨组织的影响Effect of morphine on hypothalamic-pituitary-ovarian axis and bone tissue in female rats.
郭述真,吴素慧,赵烨,程莉,祁澜,董进
摘要(Abstract)：
目的:研究吗啡对雌性大鼠性腺轴和骨组织的影响。方法:选取3月龄雌性大鼠45只,随机分为吗啡组30只和对照组15只。吗啡组采用剂量递增法皮下注射盐酸吗啡12周,对照组注射同等体积的生理盐水12周。放射免疫法测定血清FSH、LH、E2、P;免疫组织化学检测下丘脑、垂体、卵巢雌激素受体(ER)和β-内啡肽(β-EP)的表达;原位杂交方法测定下丘脑、垂体和卵巢的μ-阿片受体mRNA的表达;双能X线骨密度测量仪测量不同部位的骨密度值;测量骨代谢生化指标;对骨组织切片进行形态计量分析;并用RT-PCR方法检测骨组织中雌激素受体(ER)mRNA的变化。结果:(1)吗啡组FSH、LH、E2、P基础分泌较对照组降低(P<0·01,P<0·05,P<0·01,P<0·05);(2)吗啡组大鼠性腺轴各组织中ER平均光密度值均显著降低(P均<0·01);(3)吗啡组大鼠下丘脑、垂体β-内啡肽的含量下降,而μ-阿片受体mRNA表达增强;(4)吗啡组大鼠股骨远侧干骺端和胫骨近侧干骺端骨密度以及骨组织中ERmRNA表达均较对照组显著下降(P<0·05),组织切片观察显示,吗啡组大鼠骨小梁纤细、断裂、形态结构完整性差,骨髓腔大小不一,对照组大鼠骨小梁粗壮、饱满、形态结构完整,骨髓腔相对较小,计量分析显示,吗啡组骨小梁面积明显低于对照组(P<0·05);骨代谢生化指标结果显示,吗啡组大鼠血清钙和尿钙以及TRAP、HOP较对照组增加显著(P<0·05)。结论:长期使用吗啡对下丘脑-垂体-卵巢轴及骨组织会有不同程度的损伤。
关键词(KeyWords)： 吗啡;下丘脑-垂体系统;骨密度;骨代谢;受体,雌激素
基金项目(Foundation): 山西省科技攻关项目
作者(Author): 郭述真,吴素慧,赵烨,程莉,祁澜,董进
DOI: 10.13283/j.cnki.xdfckjz.2005.03.013
参考文献(References)：
- [1]Abs R,Verhelst J·Endocrine consequences of londg-term intrathecal adminstration of opioids[J]·J Chin Endocrinol Metab,2000,85∶2215-2222
- [2]Boukhliq R,Goodman RLA·subset of gonadotropin-relea-sing hormone neurons in the ovine medial basal hypothal-amus is activated during increased pulsatile luteinizing hormone secretion[J]·Endocrinology,1999,140∶5929-5936
- [3]Walsh JP,Clarke IJ·Blockade of the oestrogen-induced luteinizing hormone surge in ovariectomized ewes by a highly selective opioid mu-receptor agonist:evidence for site of action[J]·Neuroendocrinology,1998,67∶164-170
- [4]Bouret S,Prevot V·Mu opioid receptor mRNA expression neuronal nitric oxide cynthase-immunopositive preoptic area neurons[J]·Brain Res Mol Brain Res,2000,14,80∶46-52
- [5]王新华,纪家涛,由振东,等.吗啡成瘾大鼠脑神经核、垂体和血浆中内啡肽的变化[J].中华麻醉学杂志,1997,17∶282-285
- [6]Ammon S,Mayer P,Riechert U,et al.Microarray analysis of genes expressed in the frontal cortex of rats chronically treated with morphine and after naloxone precipitated with drawal[J].Brain Res Mol Brain Res,2003,112∶113-25