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.

作　　者：郭述真[1] 吴素慧[1] 赵烨[1] 程莉[1] 祁澜[1] 董进[1] 

机构地区：[1]山西医科大学第一医院妇产科,太原030001

出　　处：《现代妇产科进展》2005年第3期210-213,共4页Progress in Obstetrics and Gynecology

基　　金：山西省科技攻关项目

摘　　要：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。Objective:To study the influence of morphine on the function of hypothalamic-pituitary-ovarian axis and bone tissue of female rat. Methods:30 female SD rats (3 months old) were subcutaneously injected with gradually increasing dose of morphine,controlled with 15 female SD rats treated with normal saline.The serum concentrations of FSH,LH,E2 and P were measured by radio immunoassay.The change of ER(estrogen receptor)and β-EP (β-endorphin)in hypothalamus,pituitary and ovary were observed using immunohistochemistry technique and image analysis system.μ-opoide receptor mRNA was detected by in situ hybridization and bone mineral density and biochemical markers of bone metabolism in female rats were also measured.Pathomorphology of bone was observed and the expression of ER mRNA was analyzed.Results: (1) The serum concentrations of FSH,LH,E2 and P had significantly decreased(P<0.05,P<0.05,P<0.01,P<0.05)in morphine group.(2)The immunostaining density of ER in hypothalamus,pituitary and ovary was lower than that in control group.(3) Long term injection of morphine could reduce the β-EP in hypothalamus,pituitary and ovary.But the expression of μ- opioide receptor mRNA was increased significanterly than that in control group.(4) BMD in lumal vertebrate and distal femur in morphine group was significanterly decreased compared with control,while the expression of estrogen receptor α-mRNA in bone tissue in morphine group was markedly lower than that in control group.Serum tartrate-resistant acid phosphatase (TRAP) and calcium,urinary hydroxyproline(HOP) and calcium were significantly higher in morphine group than that in control group.Conclusion:Long term injection of morphine will injury the function of hypothalamic-pituitary-ovarian axis and bone tissue.

关 键 词：吗啡 下丘脑-垂体系统 骨密度 骨代谢 受体 雌激素 

分 类 号：R588.6[医药卫生—内分泌]