左炔诺孕酮宫内缓释系统对子宫腺肌病患者体内PGE_2、COX-2水平的影响

目的:研究子宫腺肌病患者置左炔诺孕酮宫内缓释系统(LNG-IUS)前后血浆前列腺素E2(PGE2)及子宫内膜组织中环氧化酶2(COX-2)的表达,探索LNG-IUS缓解子宫腺肌病痛经症状的机制。方法:采用视觉模拟评分法(VAS)和口述评分法(VRS)评定患者痛经的程度,ELISA法检测血浆PGE2含量;免疫组化法检测子宫内膜组织中COX-2的表达;Western blot法检测子宫内膜组织中COX-2蛋白含量。结果:放置LNG-IUS后,患者VAS评分及VRS评分均下降(VAS评分:22.96±21.09vs 83.81±9.82,VRS评分:0.67±0.48vs 1.41±0.64)(P0.05)。置环后血浆PGE2水平较置环前降低[(18.83±23.97)pg/ml vs(5.76±2.62)pg/ml,P0.05],子宫内膜组织中COX-2表达降低,置环前后COX-2表达阳性率分别为100%和66.7%(P0.05),置环前后COX-2蛋白表达水平灰度值具有显著差异(1177312.68±356104.82vs 310510.22±215690.66)(P=0.046)。结论:LNG-IUS缓解子宫腺肌病患者痛经症状的机制可能与抑制COX-2合成、降低PGE2水平有关。     

宫内节育器对大鼠子宫内膜血管内皮生长因子及其受体表达影响的研究

目的:研究置固定式铜宫内节育器(FCu-IUD)和固定式吲哚美辛铜宫内节育器(FICu-IUD)的大鼠子宫内膜组织中血管内皮生长因子(VEGF)及其受体Flk-1的表达。方法:采用蛋白印迹法(Western blotting)检测FCu-IUD组、FICu-IUD组大鼠子宫内膜组织VEGF及Flk-1的表达,逆转录聚合酶联反应(RT-PCR)检测各组VEGF mRNA的表达。以未置器一侧作为对照。结果:大鼠置器侧与对照侧子宫内膜均可检测到与VEGF121和VEGF165两种VEGF亚型相对应的mRNA与蛋白表达。FCu-IUD组大鼠置器侧子宫内膜VEGF121及VEGF165表达在mRNA水平和蛋白水平均显著升高,与对照侧比较差异有统计学意义(P<0.001,P<0.05)。置器侧Flk-1蛋白的表达明显高于对照侧(P<0·01)。FICu-IUD组置器侧与对照侧比较,VEGF、Flk-1蛋白及VEGF mRNA表达差异均无显著性。结论:Cu-IUD引起的子宫异常出血可能与VEGF的增加有关,吲哚美辛减少Cu-IUD引起的子宫异常出血的作用可能与通过抑制前列腺素合成从而使VEGF生成减少有关。     

NS-398与前列腺素E_2对子宫内膜异位症子宫内膜细胞环氧合酶-2mRNA表达与凋亡的影响

目的 :探讨选择性环氧合酶 2 (COX- 2 )抑制剂NS -398与前列腺素E(PGE2 )对子宫内膜异位症患者子宫内膜细胞COX -2mRNA表达与细胞凋亡的影响。方法 :以体外培养的子宫内膜细胞为研究对象 ,分别用NS- 398与PGE2 处理。采用RT- PCR法、MTT法、酶联免疫吸附试验 (ELISA)和流式细胞术 ,检测刺激前后COX -2mRNA表达量、细胞增殖、凋亡与细胞周期分布情况以及上清液中凋亡抑制蛋白Bcl 2与PGE2 的释放量。结果 :NS- 398以剂量与时间依赖方式抑制COX -2mRNA的表达以及PGE2 与Bcl -2的分泌 ,抑制子宫内膜细胞增殖 ,诱导细胞凋亡 ,改变细胞周期分布 ,增加G0 /G1期细胞的比例。PGE2以时间与剂量依赖方式刺激子宫内膜细胞的COX- 2mRNA的表达 ,使Bcl- 2释放增加。同时 ,PGE2 可以逆转NS- 398对子宫内膜细胞的抑制作用 ,细胞增殖重新活跃 ,改变细胞周期分布 ,减少G0 /G1期细胞的比例 ,抑制细胞凋亡。结论 :COX- 2选择性抑制剂NS- 398,促进细胞凋亡 ,抑制细胞增殖 ,其机制可能与抑制COX -2的表达 ,降低PGE2 以及Bcl- 2释放 ,和改变细胞周期有关。PGE2 在体外能够刺激子宫内膜细胞COX- 2的表达升高 ,促进细胞增殖 ,抑制细胞凋亡。     

放置宫内节育器对子宫内膜血管内皮生长因子及其激酶受体表达及微血管密度变化的影响

目的探讨放置固定式带铜宫内节育器(FCu-IUD)和含吲哚美辛FCu-IUD(FICu-IUD),对子宫内膜组织中血管内皮生长因子(VEGF)及其激酶受体(KDR)表达以及微血管密度(MVD)变化的影响及意义.方法采用免疫组化法及原位杂交法,检测放置FCu-IUD妇女(10例,FCu-IUD组)及放置FICu-IUD妇女(10例,FICu-IUD组)放置IUD前后子宫内膜VEGF、VEGF mRNA及KDR的表达,并计数子宫内膜MVD.结果 FCu-IUD组放置IUD后,VEGF及KDR蛋白为0.568±0.027,0.244±0.022,均高于放置IUD前的0.357±0.032,0.215±0.029,放置IUD前后比较,差异有显著性(P<0.05).FCu-IUD组放置IUD前VEGF mRNA表达为0.359±0.022,低于放置IUD后的0.425±0.019,放置IUD前后比较,差异有显著性(P<0.05).FICu-IUD组放置IUD前后VEGF、KDR蛋白及VEGF mRNA表达比较,差异无显著性(P>0.05). FCu-IUD组放置IUD后MVD为19.8±4.8,明显高于放置IUD前的15.4±2.8,且与VEGF蛋白的表达呈正相关关系(r=0.847,P<0.01).FICu-IUD组放置IUD前后MVD比较,差异无明显性(P>0.05).结论放置FCu-IUD可促进子宫内膜VEGF及KDR的表达,FICu-IUD可抑制子宫内膜VEGF及KDR的生成.VEGF及KDR可能参与了FCu-IUD 及FICu-IUD所引起的子宫内膜微血管结构和功能的改变.     

左炔诺孕酮宫内缓释系统治疗功能失调性子宫出血的临床观察

目的:观察左炔诺孕酮宫内缓释系统(LNG-IUS)治疗功能失调性子宫出血的临床效果。方法:48例确诊为功能失调性子宫出血的患者,放置LNG-IUS。置宫内节育器前后均行宫腔镜检查、月经量评分、测量子宫内膜厚度;检测卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)和孕酮(P)浓度及子宫内膜雌、孕激素受体(ER/PR)。结果:置宫内节育器3个月后,月经量明显减少,PBAC法月经量评分由置宫内节育器前(128.9±41.5)降至(52.2±13.8),具有统计学意义(P<0.01);子宫内膜由(12.9±4.2)mm降至(8.4±2.0)mm,差异具有统计学意义(P<0.05)。置宫内节育器6个月后,宫腔镜下观察,子宫内膜菲薄,病理显示内膜呈轻度分泌现象及间质蜕膜样变;ER、PR的表达均显著下调(P<0.01)。结论:LNG-IUS能有效地减少月经量,对增生的子宫内膜具有逆转作用,治疗功能失调性子宫出血效果好。     

应用宫内节育器的妇女沙眼衣原体感染与子宫内膜中铜含量的关系

目的:探讨女性生殖道沙眼衣原体(CT)感染与宫内节育器(IUD)种类及内膜中铜含量的关系。方法:用聚合酶链反应检测65例置含铜IUD及97例置不锈钢单环的妇女宫颈分泌物CT;对因症取出IUD的20例妇女,取器后刮取子宫内膜,用原子吸收分光光度法测子宫内膜铜含量。结果:放置含铜IUD者CT感染率(3.1%)明显低于置不锈钢单环者(12.3%),P<0.05;放置含铜IUD的妇女子宫内膜铜含量明显高于置不锈钢单环者(P<0.05)。结论:含铜IUD对生殖道CT感染有抑制作用。含铜IUD可能通过释放的铜离子来发挥抗CT作用。     

左旋18—甲基炔诺酮T型宫内节育器对子宫内膜血管内皮细胞因子Ⅷ活…

本研究检测了３４例正常育龄妇女放置左旋１８－甲基炔诺酮宫内节育器（ＬＮＧ－ＩＵＤ－２０）前，后子宫内膜血管内皮细胞因子Ⅷ（ＦⅧ）的活性。ＰＡＰ法染色，计算机数字化图像分析系统测定ＦⅧ活性的灰度值。结果：置器１２个月后，子宫内膜血管内皮细胞ＦⅧ活性大部分较放器前明显减弱（Ｐ＜０．００１），少数前后不变。提示ＬＮＧ－ＩＵＤ－２０可能干扰了子宫内膜血管内皮细胞ＦⅧ的合成，释放。     

IUD对妇女月经血浆中去甲肾上腺素及肾上腺素含量的影响

为进一步探讨宫内节育器(IUD)对子宫中肾上腺素能神经系统的影响,作者用改良荧光分光光度法测定了置IUD前后妇女月经血浆中去甲肾上腺素(NE)及肾上腺素(E)含量。结果表明,妇女置IUD后,经血中去甲肾上腺素含量明显高于置器前的含量,且这种增加与置器后月经血量的增加相关,提示宫内节育器对妇女子宫中肾上腺素能神经系统有影响,并被认为可能是导致置器后月经过多的原因之一。     

记忆合金药铜宫内节育器对兔子宫内膜超微结构的影响

目的:研究记忆合金药铜节育器对兔子宫内膜超微结构的影响。方法:雌性日本大耳白兔随机分为3组,实验组记忆合金药铜节育器和对照组不锈钢药铜节育器各18只,假手术对照组6只,通过手术放置节育器于兔子宫腔内,术后1、3、6个月处死兔,取出子宫,扫描和透射电子显微镜下观察放置节育器处的子宫内膜。结果:放置节育器的兔子宫内膜均可见上皮细胞的形态和结构发生改变。扫描电子显微镜下,上皮细胞的变化随节育器放置时间和受压程度的增加而增加,可逐渐出现细胞表面压平、变形,微绒毛稀疏、消失;较长时间放置,可引起上皮细胞损坏、脱落。透射电子显微镜下2种节育器引起的细胞形态和结构的改变相似,主要是内质网扩张,细胞核肿胀,质膜溶解,严重的可见上皮细胞脱落现象。细胞内超微结构的损伤亦随节育器放置时间和受压程度的增加而加重。但基膜始终损伤较轻微,基膜下的间质未观察到明显异常的形态学变化。结论:记忆合金药铜节育器与不锈钢药铜节育器对兔子宫内膜超微结构的影响相似。     

释放左旋18甲基炔诺酮宫内节育器对三苯氧胺引起子宫内膜病变的治疗

目的　探讨释放左旋 18甲基炔诺酮宫内节育器 (LNG -IUD ,Mirena)对服用三苯氧胺的乳腺癌患者子宫内膜病变的疗效和不良反应。方法　对 2 7例绝经后乳腺癌患者 ,术后服用三苯氧胺 (1～ 10 8个月 )引起的子宫内膜增厚进行临床资料分析 ,经过宫腔镜及诊断性刮宫除外子宫内膜癌后 ,宫内放置Mirena ,每 1～3个月行阴道B超 1次 ,观察放置前后子宫内膜厚度的变化及不良反应。结果　 2 7例置Mirena患者 ,从放置前子宫内膜平均厚度 (1 30± 0 4 2 )cm ,到放置后 3、6及 12个月以上时 ,子宫内膜平均厚度分别为 (0 95± 0 2 9)cm、(0 93± 0 36 )cm及 (0 78± 0 2 2 )cm ,P值均 <0 0 1。不良反应主要为不规则阴道流血 ,但大多可自行停止。结论　释放左旋 18甲基炔诺酮宫内节育器对服用三苯氧胺绝经后乳腺癌患者增厚的子宫内膜具有治疗作用 ,不良反应轻微。左旋 18甲基炔诺酮可以保护服用三苯氧胺的绝经后乳腺癌患者的子宫内膜。     

Suppression of IL-1beta-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells

OBJECTIVE: Over-production of cyclooxygenase-2 (COX-2) plays an important role in the positive feedback loop that leads to proliferation and inflammation in endometriosis. Following our observation that histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and valproic acid (VPA) can suppress proliferation of endometrial stromal cells, we sought to determine whether TSA suppresses IL-1beta-induced COX-2 expression in endometrial stromal cells. STUDY DESIGN: In vitro study using a recently established immortalized endometrial stromal cell line. The stromal cells were pretreated with TSA before stimulation with IL-1beta, and COX-2 gene and protein expression was measured by real-time quantitative RT-PCR and Western blot analysis, respectively. RESULTS: IL-1beta stimulated COX-2 expression in a concentration-dependent manner in endometrial stromal cells. The induced COX-2 gene and protein expression were suppressed by TSA pretreatment. CONCLUSIONS: TSA suppresses IL-1beta-induced COX-2 gene and protein expression in endometrial stromal cells. This finding, coupled with the findings that TSA and another HDACI, valproic acid, suppress proliferation and induce cell cycle arrest, suggests that HDACIs are a promising class of compound that has therapeutic potential for endometriosis.     

消炎痛Vcu200 IUD减少月经过多的机理

自１９９２年１１月至１９９５年６月，对４６例放置无消炎痛ＶＣｕ２００ＩＵＤ及２４例含消炎痛ＶＣｕ２００ＩＵＤ妇女的子宫内膜中６－ｋｅｔｏ－ＰＧＦ１α、ＴＸＢ２及纤溶指标包括ｔ－ＰＡ、ＰＡＩ、ＰＫ、ＰＬＧ、Ｄ－Ｄ及ＦＤＰ的水平进行测定，同时作光、电镜观察置器后ＩＵＤ对子宫内膜的影响。结果：１．无消炎痛ＶＣｕＩＵＤ３月组置器后６－ｋｅｔｏ－ＰＧＦ１α／ＴＸＢ２比值明显高于置器前（Ｐ＜０．０５），ｔ－ＰＡ、ＰＫ、ＰＬＧ、Ｄ－Ｄ及ＦＤＰ均非常明显低于置器前水平（Ｐ＜０．ｏ１～０．００１）。２．无消炎痛ＶＣｕＩＵＤ＞６月组置器后只ｔ－ＰＡ、ＰＫ、ＦＤＰ明显低于置器前水平（Ｐ＜０．０１～０．００１），其余指标均无统计学差异。３．放置合消炎痛ＶＣｕＩＵＤ３个月后６－ｋｅｔｏ－ＰＧＦ１α、ＴＸＢ２及各项纤溶指标与置器前比均无统计学意义。４．子宫内膜形态学变化与置器前相比，表现为血管内血栓形成减少及末梢小血管腔扩大。根据上述结果，置器后内膜中６－ｋｅｔｏ－ＰＧＦ１α／ＴＸＢ２值升高，与ｔ－ＰＡ水平下降可能是置器后月经过多的主要原因，尤以前者起主导作用。本文并对消炎痛ＩＵＤ减少月经过多的作用机理进行了讨论。     

Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and progesterone (PR), p53, ki67, and neu protein in endometrial cancer

OBJECTIVE: We aimed at investigating by immunohistochemistry the relationship between cyclooxygenase-2 (COX-2) and estrogen (ER), and progesterone (PR) receptors in a single institution series of 90 primary untreated endometrial cancer patients. The simultaneous assessment of p53 protein, ki67, and neu protein has been carried out. METHODS: Immunohistochemistry was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against human COX-2, anti-ER (clone 1D5), and anti-PR (clone 1A6) monoclonal antibodies, anti ki67 (clone MIB-1) and p53 (clone DO-7), and polyclonal antibody anti human c-erbB2/neu. RESULTS: There was no difference in the distribution of COX-2, p53, and neu positive cases according to ER or PR positivity, while the percentage of ki67 positive endometrial tumors was significantly higher in ER negative versus ER positive tumors (54.5% versus 31.6%, P value = 0.044). ER and PR positive tumors showed a statistically significant association with clinicopathological parameters of better clinical outcome. There was no clear association between COX-2 positivity and any of the clinicopathological features. The percentage of ki67, p53, and neu positive tumors was found to be strictly related to more aggressive features. Only advanced stage of disease was found to be a predictor of poor prognosis (P value = 0.034). None of the biological parameters examined was shown to be associated with patient outcome. CONCLUSIONS: We showed that COX-2 expression is not correlated with ER, PR, p53, and neu, thus suggesting that COX-2-mediated activities may follow independent pathways. Our findings provide the rationale to design trials based on the combination of antihormones with inhibitors of COX-2 and neu in recurrent/metastatic endometrial cancer.     

The benefit of endometrial biopsy before IUD insertion

131 patients aged 25-35 followed from 1969-84 underwent endometrial biopsies under antibiotic cover preliminary to insertion of IUDs. 125 subsequently had IUDs inserted, including 10 Dalkon Shields, 50 Gravigards, and 66 copper 200, Gyne-T, or Nova T devices. All IUDs were inserted in the 1st 10 cycle days under a 3-day antibiotic cover. The 131 biopsies revealed 18 simple endometrial hyperplasias, 1 glandulo- cystic hyperplasia, and 5 endometrial polyps. The hyperplasias were treated with a progestin on cycle days 15-25 for 3-6 months and a curettage was performed for the polyps. No cases of endometritis were found in nulligestes. The 11 patients with latent endometritis were treated with antibiotics for 10 days and were vaccinated with an antipyogenic. A repeat endometrial biopsy was done to confirm disappearance of the endometritis before the IUD was inserted. The 126 IUD users were followed for 6 years on average. 2 cases of salpingitis and an adnexal reaction were observed. 2 of the 3 were treated with antibiotics and had no complications. The 3rd underwent tubal microsurgery after which she became pregnant. The IUD was removed in all 3 cases at the onset of symptoms. 1 of the 3 patients did not have a preliminary endometrial biopsy before the IUD was inserted. Despite the small sample size, it appears that a preliminary endometrial biopsy can reduce the infection rate among IUD users to that of the general female population.     

COX-1 and COX-2 expression in stage I and II invasive cervical carcinoma: relationship to disease relapse and long-term survival

COX-1 and COX-2 are members of the cyclooxygenase (COX) family, which influence tumor invasion and apoptosis. The objective of the study was to assess the relationship between COX-1 and COX-2 expression in early-stage disease and subsequent disease relapse and long-term survival. Women with FIGO stage I and II cervical carcinoma, younger than 50 years, treated between 1981 and 1990 were included. COX-1 and COX-2 expressions in the tumors were assessed by immunohistochemistry. COX-1 and COX-2 were expressed in 61% (17/28) and 57% (16/28) of tumors, respectively. COX-1 nonexpressers showed an improved overall survival compared to expressers (log-rank test, P= 0.09). There was no significant difference in the overall survival in COX-2 nonexpressers compared to expressers (P= 0.6). Out of eight women with disease relapse, COX-1 or COX-2 expression was noted in six of eight tumors, and both were expressed in five of eight tumors. Our preliminary data suggest an adverse prognosis with COX-1 expression in early-stage cervical carcinoma and a trend toward COX-1 expression in disease relapse. The association between COX-2 expression and a worse prognosis was not proven in this study.     

Prospective comparison study of levonorgestrel IUD versus Roller-Ball endometrial ablation in the management of refractory recurrent hypermenorrhea

OBJECTIVE: To compare endometrial ablation and levonorgestrel-IUS for treatment of refractory reccurrent hypermenorrhea. STUDY DESIGN: 30 patients with refractory recurrent hypermenorrhea were included in a prospective controlled comparative study. A transcervical Roller-Ball ablation was carried out in 15 patients after a 2-months GnRH analog pretreatment. A levonorgestrel IUD (MIRENA(R), Schering AG Berlin, Germany) was inserted in 15 patients for the treatment of hypermenorrhea. In a follow-up of the bleeding behavior over 12-24 months a reduction of bleeding was achieved in 14 of 15 patients after Roller-Ball ablation and in 11 of 15 patients after levonorgestrel IUD insertion. The amenorrhea rates are roughly the same in both groups. Side effects of levonorgestrel IUS were rare and mostly temporary. CONCLUSIONS: The insertion of a levonorgestrel IUD for the local hormonal treatment of recurrent hypermenorrhea refractory to oral treatment can be tried before endometrial ablation. The MIRENA(R) device is particularly advantageous for younger patients who might wish to have more children. The levonorgestrel IUD treatment can replace approx. 75% of endometrial ablations.     

The morphometric study of endometrial spiral arterioles before and after insertion of gamma CuI and TCu 220C intrauterine devices

OBJECTIVE: To investigate the morphologic changes of endometrial spiral arterioles and its relationship with bleeding pattern after insertion of gamma-shape copper indomethacin-medicated (gamma CuI) and T-shape copper (TCu 220C) intrauterine devices (IUD). METHODS: Endometrium specimens of late secretory phase were obtained from fertile age women: 10 from preinsertion, 10 obtained after insertion of TCu 220C IUD, and 9 obtained after insertion of gamma CuI IUD. Samples were sectioned serially and morphometric analysis of endometrial spiral arterioles was performed under light microscope. RESULTS: The average cross section area (Area), maximum diameter (Dmax) and minimum diameter (Dmin) of spiral arterioles in both spongeous and dense layers of endometrium increased significantly after insertion of TCu 220C IUD. After insertion of gamma CuI IUD, the Area and Dmax increased in dense layer only, though less obviously than that occurred in TCu 220C group. However, the Dmin increased more obviously in both spongeous and dense layers than after insertion of TCu 220C IUD, implying that the shape of spiral arterioles was more regular in gamma CuI group. CONCLUSION: gamma CuI IUD has less effects on the morphological changes of endometrial spiral arterioles, and this may relate to its indomethacin-contained which causes less bleeding.     

Clinical effects in 1136 cases of Beijing silicon rubber IUD and its effect on the endometrium]

Beijing Silicon Rubber IUD was designed by Xuan Wu Hospital and Beijing Silicon Rubber Manufacturing Research Institute in 1980. Animal experiments of the silicon rubber were done, and toxic effect studied before clinical use. 1136 cases were reported at the end of 12 months by 6 hospitals in Beijing. The followup rate was 93.75%. Life table of 12 months showed the cumulative continuation rate of the IUD was 82.45%, pregnancy rate 4.5%, expulsion rate 8.49%, removal for medical cause 3.9%, and removal for personal reasons 0.64%. Among the side effects, menstrual irregularity was 5.03%, blood discharge 6.35%, dysmenorrhea 11.95%, backache 31.1%, and leucorrhea 18.12%. Menstrual blood loss was measured in 30 cases before and after 1, 2, 3 months of insertion. The mean blood loss before insertion was 51.96 ml (51.71 +or- 15.95), while 1 month after insertion it was 62.9 ml (70.59 +or- 26.81), 2 months after insertion 71 ml, and 3 months after insertion 75 ml. The morphological endometrial change as compared with that by induced stainless steel ring is not much heavier especially in regard to glandular and stromal changes. The endometrial cytologic count of white cells of the IUD group (34 cases) in comparison with that of the control group (36 cases) was about twice as much in number. As Moyer reported, the endometrial cell count of IUD cases was about 6-10 times that of control cases. The authors consider that the cellular reaction of this IUD is not much greater than that of other types of IUDs.