【作者】 杨艳青；

【导师】 沈鸿敏； 徐素欣；

【作者基本信息】 河北医科大学 ， 妇产科学， 2003， 硕士

【摘要】 目的:(1)测定高催乳素血症妇女外周血CD4~+T淋巴细胞?CD8~+T淋巴细胞?CD3-CD16~+CD56~+NK细胞水平的变化,分析高催乳素血症状态下各淋巴细胞的变化规律,并检测外周血IL-2水平?血清中抗心磷脂抗体,探讨高催乳素血症妇女免疫功能状态;(2)测定高催乳素血症妇女外周血皮质醇(cortisol Cs)?肾上腺皮质激素释放激素(ACTH)水平及两者水平的日节律变化规律,探讨高催乳素血症状态时下丘脑-垂体-肾上腺轴(H-P-A)功能改变;(3)测定高催乳素血症妇女生殖激素水平,探讨高催乳素血症对生殖激素水平的影响(4)通过对高催乳素血症妇女免疫及内分泌各相应代表参数的变化规律及其相关性分析,综合评估神经-内分泌-免疫平衡在高催乳素血症发病中的作用及变化?(5)探讨催乳素作为神经递质?内分泌激素以及细胞因子的多重作用?方法:选择34例高催乳素血症患者为病例组,20例健康育龄妇女为对照组进行研究?(1)流式细胞术检测34例高催乳素血症妇女,20例健康育龄妇女外周血CD4~+T?CD8~+T淋巴细胞?CD3-CD16~+CD56~+NK细胞水平;(2)酶放大化学发光免疫分析(IMMULITE)法检测34例高催乳素血症妇女及20例健康育龄妇女外周<WP=4>血清中皮质醇和ACTH(同日8:00AM?4:00PM)水平;(3)放射免疫分析法检测高催乳素血症妇女溴隐亭治疗前后及健康育龄妇女外周血清中IL-2水平;(4)酶联免疫吸附试验(ELISA)法检测34例高催乳素血症妇女及20例健康育龄妇女血清中抗心磷脂抗体IgG?IgA?IgM;(5)磁性分离酶免疫法检测34例高催乳素血症妇女及20例健康育龄妇女血清中促卵泡素(FSH)?黄体生成素(LH)?雌二醇(E2)?睾酮(T)?催乳素水平? 结果:(1)高催乳素血症妇女外周血CD4~+T淋巴细胞水平降低,与对照组比较有显著性差异(P<0.05),病例组中闭经组与对照组比较,差异也有显著意义(P<0.05),而肿瘤组?溢乳组分别与对照组比较,均无显著性差异(P>0.05,P>0.05)?病例组内闭经组与有月经组比较?肿瘤组与非肿瘤组?溢乳组与无溢乳组比较比较,均无显著性差异(P>0.05,P>0.05,P>0.05);(2)高催乳素血症妇女外周血CD3~+T淋巴细胞水平较对照组水平降低?CD8~+T淋巴细胞水平较对照组水平有所升高,但分别与对照组比较,均无显著性差异(P>0.05,P>0.05)?(3)高催乳素血症妇女外周血中CD4~+T/CD8~+T比值降低,与对照组比较有显著性差异(P<0.05)?其中闭经组与有月经组比较?肿瘤组与非肿瘤组?溢乳组与无溢乳组比较,均无显著性差异(P>0.05,P>0.05,P>0.05)?(4) 高催乳素血症妇女外周血中CD3-CD16~+CD56~~+NK细胞水平与对照组比较无显著性差异(P>0.05)? (5) 高催乳素血症妇女外周血IL-2水平升高,与对照组比较有显著性差异(P<0.01)?有10例患者经溴隐亭治疗至催乳素水<WP=5>平正常并恢复排卵后,测其 IL-2水平降低,与对照组比较无显著差异(P>0.05)?其中,闭经组病人与对照组比较有显著性差异(P<0.05),而肿瘤组?溢乳组分别与对照组比较,均无显著性差异(P>0.05,P>0.05)?闭经组与有月经组比较?肿瘤组与非肿瘤组?溢乳组与无溢乳组比较,无显著性差异(P>0.05,P>0.05,P>0.05)?(6)高催乳素血症妇女同日4:00PM外周血皮质醇?ACTH水平升高,8:00AM ACTH水平降低,分别与对照组比较,均有显著性差异(P<0.05, P<0.01, P<0.01);(7)高催乳素血症妇女外周血ACTH分泌异常,同日8:00AM及4:00PM ACTH水平比值接近于1:1,失去正常两点间约2:1的节律?(8)高催乳素血症妇女外周血催乳素/皮质醇比值升高,与对照组比较有显著性差异(P<0.01)?(9)高催乳素血症妇女血清中抗心磷脂抗体IgG阳性率明显增高,与正常对照组比较有显著性差异(P<0.05)?(10)高催乳素血症妇女闭经时或卵泡期生殖激素水平显示雌二醇(E2)水平明显降低,与正常对照比较有显著差异(P<0.01),其中闭经组较有月经组降低?肿瘤组较非肿瘤组降低?溢乳组较无溢乳组降低(P<0.01,P<0.01,P<0.01)?病例组患者体内升高的催乳素水平在各组间均有差异,闭经组?肿瘤组?溢乳组分别高于有月经组?非肿瘤组及无溢乳组(P<0.01,P<0.01,P<0.01)?(11)相关分析:正常对照组中CD3+T水平与皮质醇(8:00AM)水平呈负相关(r=-0.496 P=0.026),CD8+T水平与皮质醇(8:00AM)呈负相关(r=-0.456, P=0.043),IL-2水平与ACTH<WP=6>(8:00AM?4:00PM)水平均呈正相关(r=0.609 P=0.004,r=0449 P=0.047)?而病例组中降低的ACTH(8:00AM)水平与升高的催乳素水平呈负相关(r=-0.393 P=0.022),闭经组降低的ACTH(8:00AM)水平与降低的CD4+T水平呈正相关(r=0.466 P=0.044),其皮质醇(8:00AM)水平较正常对照组水平虽然无显著性差异,却与降低的E2水平呈正相关(r=0.522 P=0.022)? 小结:高催乳素血症妇女机体内存在着免疫系统机能异常状态?细胞免疫?体液免疫功能均有异常的改变?体内免疫促进与免疫抑制调节作用失衡,自身抗体增多,IL-2水平高于正常?H-P-A轴分泌水平及节律失常?催乳素水平不同程度升高,同时E2水平降低,并以伴有闭经和/或溢乳?催乳素肿瘤者变化更显著?皮质醇?ACTH水平与催乳素?E2?淋巴细胞亚群之间存在相关性?提示高催乳素血症妇女的神经-内分泌-免疫网络失衡?催乳素可能作为内分泌激素?细胞因子及神经递质发挥了多重的复杂作用?更多还原

【Abstract】 Objective: 1.To observe the levels of CD4~+T lymphocyte , D8~+T lymphocyte, CD3-CD16~+CD56~+NK cell in peripheral blood of patients with hyperprolactinemia and determine the concentrations of interleukin-2 (IL-2) and anticardiolipin IgG, IgA, IgM in the serum of hyperprolactinemic patients,then investigate the immunal function and it’s change rules of hyperprolactinemia. 2. To determin the levels of cortisol (Cs) and adrenocorticotropin (ACTH) and their diurnal rhythm , then investigate the function of hypothalamic-pituitary-adrenal (H-P-A) axis and the changes in the condition of hyperprolactinemia. 3. The levels of sex hormones were tested in patients with hyperprolactinemia in order to investigate the influence caused by high level prolactin. 4. To analyse the correlations between each representative parameter and their changes, then generally evaluate the neuro-endocrine-immunoregulatory network’s functions and changes in women with hyperprolactinemia5.Investigate multiple roles of prolactin as a cytokine,an endocrine hormone and aneurotransmitters <WP=8>Methods: Thirty-four hyperprolactinemic patients and twenty normal fertile women were selected in this study. 1.The levels of CD4~+T lymphocyte, CD8~+T lymphocyte, CD3-CD16~+CD56~+NK cell was test with the method of flow cytometre. 2.Enzyme chemiluminescent immunoassays were employed to test the levels of cortisol and ACTH (8:00AM and 4:00PM in the same day) in thirty-four patients with hyperprolactinemia and twenty normal fertile women. 3.Radioimmunoassy was used to test the level of IL-2 in hyperprolactinemic women (pro-therapy and post-therapy) treated with bromocriptine and twenty normal fertile women. 4.Enzyme linked immunoabsorbent assay was used to test anticardiolipin in thirty-four patients with hyperprolactinemia and twenty normal fertile women. 5.The sex hormones including follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T) and prolactin (PRL) in the serum were examined with immunoenzymetric assay (magnetic solid phase). Results: 1. The CD4~+T lymphocyte cell is significantly reduced in hyperprolactinemic patients compared to normal subjects (P<0.05). Of all the patients, the CD4~+T level of the amenorrhea group is significantly reduced compared to normal controls (P<0.05), but it is not reduced neither in the tumor group nor the galactorrhea group compared to normal controls (P>0.05, P>0.05).<WP=9>Meanwhile,the level of CD4~+T was not different between the amenorrhea and the non-amenorrhea group, the galactorrhea and the non-galactorrhea group, the tumor and the non-tumor group (P>0.05,P>0.05,P>0.05). 2. The CD3~+ level of the hyperprolactinemic patients was lower and the CD8~+T level was higher both than that of the normal controls (P>0.05,P>0.05), but no significant difference of CD3~+T and CD8~+T levels was found between the patients and the normal subjects respectively (P>0.05,P>0.05). 3. As a consequence of changes in the level of CD4~+T and CD8~+T, hyperprolactinemic patients have a lower ratio of CD4~+T/ CD8~+T than normal control (P<0.05). There are no difference about the ratio between the amenorrhea and the non-amenorrhea group, the galactorrhea and the non-galactorrhea group, the tumor and the non-tumor group (P>0.05,P>0.05,P>0.05). 4. The level of NK cell is not different between hyperprolactinemic patients and normal subjects (P>0.05). 5. Hyperprolactinemic patients have a higher level of IL-2 than that of normal control and so do the amenorrhea group (P<0.01,P<0.05). The level of serum IL-2 (post-therapy) was not significantly different from control group (P>0.05). 6. In hyperprolactinemic patients we observed higher cortisol and ACTH levels at 4:00PM and lower ACTH level at 8:00AM compared to controls (P<0.05,P<0.01,P<0.01).Meanwhile,we observed abnormal secretion diurnal rhythm of cortisol and ACTH.There was<WP=10>no nomal ACTH peak phase at 8:00AM. The normal rhythm about 2 to 1 (8:00AM to 4:00PM) changed to 1 to 1. We also found a higher ratio of p更多还原