含消炎痛铜宫内节育器对兔子宫内膜的形态学影响

含消炎痛铜宫内节育器对兔子宫内膜的形态学影响陈和平，刘锋，李有明，唐莉，易永芬为了探索减少宫内节育器（ＩＵＤ）出血的问题，将消炎痛缓释系统置入不锈钢含铜ＩＵＤ内，置入兔子官腔内，初步观察了该器对兔子宫内膜形态的影响。１．材料：取金属单环，不锈钢螺旋节...     

放置含铜宫形器、TCU_（220C）和圆形宫内节育器后人子宫内膜形态的比较

对含铜宫形器（ＵＣＤｃｕ２００）、ＴＣＵ２０Ｃ及圆形器３种宫内节育器行置器后子宫内膜形态学的对比研究。结果：３０例ＵＣＤｃｕ２００子宫内膜组织标本，均见弥散分布的棕黑色颗粒，铜染色阳性、弥漫充血、出血及炎性细胞浸涧随时间的推移而减轻。腺体发育不同步，其中１０例可见腺上皮灶性鳞化及增生，在置器后４～５年的标本中间质出现明显纤维化改变。２０例ＴＣＵ２２０ｃ子宫内膜组织标本于置器１年的有较重的充血、出血、炎性细胞浸润，棕黑色颗粒大、量多，铜染色仍阳性，反应较ＵＣＤｃｕ２００重。圆形器１５例，内膜组织所见较上述二者明显为轻。结果表明，宫内节育器对子宫内膜的影响不仅与形状有关，也与铜是否直接接触子宫内膜有明显的相关性。     

药铜宫内节育器的恒河猴实验研究

实验选用恒河猴放置药铜宫内节育器（ＬＮＧ－Ｃｕ－ＩＵＤ：ＬＮＧ６μｇ／ｄ，Ｃｕ２００ｍｍ２）６个月，以观察其节育效果及月经情况。结果：节育效果好，无妊娠、无脱落；月经改变表现为出血不规则、经量减少及闭经，但取器后即恢复正常；宫腔冲洗液ＰＧｓ放免测定，置器前后ＰＧＥ２、ＰＧＦ２α、６－ｋｅｔｏ－ＰＧＦ１α浓度无显著差异，ＴＸＢ２明显上升，６－ｋｅｔｏ－ＰＧＦ１α／ＴＸＢ２比值下降，提示ＬＮＧ－Ｃｕ－ＩＵＤ导致周期出血减少可能与此有关；置器后子宫内膜上皮细胞和若干酶活性不同程度受抑。结果提示：兼释ＬＮＧ和Ｃｕ２＋的ＩＵＤ具有节育效果可靠、经血量少等优点，但对月经的影响尚需深入研究。     

铜宫内节育器对大鼠子宫内膜毛细血管脆性通透性及内膜血流量的影响

对６３只置铜宫内节育器大鼠子宫毛细血管脆性、通透性和内膜血流量进行了分区测量。结果显示，１４例墨汁高压灌流标本的环压区内膜均有出血，出血率为１００％，与其它各区相比差异显著；千宫组织中伊文思蓝的含量环压区和邻环区明显高于其他各区。应用比受体阻断剂后，环压区与其他各区仍有显著差异；子官内膜的血流量以对压区作为１００％，对邻区、对远区、远环区和邻环区分别为１０９．４％、１１６．６％、１１８．９％和１０７．６％。环压区为８３．４％，显著低于以上各区。这表明铜宫内节育器可引起与其接触的内膜毛细血管脆性、通透性增加，血流量减少，可能是带器出血的重要原因。     

高效液相色谱法测定载药宫内节育器消炎痛体外释放量

高效液相色谱法测定载药宫内节育器消炎痛体外释放量刘铁钢陈先丽闵薇徐人庆放置宫内节育器（ＩＵＤ）的主要副反应是不规则出血和腹部疼痛，我所于１９９３年研制了以聚醋酸乙烯酯（ＥＶＡ）为载体的缓释吲哚美辛（ｉｎｄｏｍｅｔｈａｃｉｎ，消炎痛）ＩＵＤ。经临床观察...     

血管内皮生长因子在子宫内膜的表达及调控

血管内皮生长因子 ( vascular endothelial growth factor,VEGF)为特异性促血管内皮细胞丝裂原并具促血管通透性作用。 VEGF及其受体在子宫内膜中表达 ,受雌孕激素、缺氧、c AMP的调节 ,其与生理性月经后的内膜修复、胚胎植入及子宫内膜癌、内膜异位症、子宫异常出血密切相关     

宫内节育器取出后的生育能力

宫内节育器(IUD)是安全、有效、可逆的避孕方法,是我国女性常用的避孕措施。随着二孩政策开放,一些妇女使用宫内节育器避孕取出后出现了继发不孕的问题。放置宫内节育器对女性再生育的影响成为妇产科医生的关注焦点。本文围绕宫内节育器取出后的生育能力分别从宫内节育器与输卵管不孕、宫内节育器对子宫内膜的影响以及宫内节育器与不良妊娠等方面进行综述。     

消炎痛宫内节育器对大鼠和兔子宫内膜影响的形态学观察

为了探讨消炎痛宫内节育器（ＩＵＤ）对子宫内膜的影响，给ＳＤ大鼠和新西兰兔经腹放置消炎痛－Ｃｕ－ＩＵＤ、Ｃｕ－ＩＵＤ、消炎痛－ＩＵＤ或硅橡胶ＩＵＤ，分别于置器后１、３、６个月解剖取子宫，行光镜和电镜观察，并与不放ＩＵＤ动物作对照。结果：消炎痛－Ｃｕ－ＩＵＤ放置１～６个月后子宫内膜无明显病理改变，与对照组相似，消炎痛及硅橡胶ＩＵＤ也都未引起子宫内膜病理改变，Ｃｕ－ＩＵＤ组可见组织水肿、纤维组织增生及散在白细胞等轻度病理变化。血管分布状态有一些变化，消炎痛－ＩＵＤ微血管以正常和收缩状态为主，Ｃｕ－ＩＵＤ则见微循环扩张，以微血管舒张状态为主（７０％），与消炎痛－Ｃｕ－ＩＵＤ组及对照组比较，有显著性差异（Ｐ＜０．０１）。结论：消炎痛对子宫内膜无不良影响     

活性元宫型药铜宫内节育器铜离子及药物体外释放的研究

目的比较含吲哚美辛(IMC)和含双氯芬酸钠(DFS)的两种含铜宫内节育器(IUD)在模拟宫腔液中的铜离子和药物的释放规律,以及铜丝浸泡后的表面形貌改变差异。方法将含IMC或含DFS的元宫药铜288型宫内节育器分别浸泡在37℃的50ml的模拟宫腔液中,定期换液。采用电感耦合等离子体发射光谱法及紫外可见分光光度仪分别测试了不同浸泡时间后模拟宫腔液中的铜离子(Cu2+)浓度,及吲哚美辛、双氯芬酸钠浓度,并用扫描电子显微镜观测了元宫药铜宫内节育器在模拟宫腔液中浸泡10d、30d及60d后的铜丝表面形貌。结果 IMC-IUD和DFS-IUD的铜离子释放均是前期快,后期慢,两组的Cu2+的累计释放量在前、后期差别不大,差值变化较小(P0.05),但在5~33d有显著差别(P0.05);DFS在释放介质中呈现双相释放,20d后基本达到稳态,每24h平均释放量约为(0.134±0.025)mg,而IMC的早期释放则呈不规则状态,前7d内的释放量显著少于DFS(P0.05),8d后每天释放量又显著大于DFS(P0.05),20d后IMC的24h平均释放量约为(0.675±0.175)mg;两组浸泡后的铜丝表面形貌均呈现明显的不均匀腐蚀现象。结论DFS-IUD中的DFS体外释放较IMC-IUD释放IMC更为恒定。     

释放左旋18-甲基炔诺酮(20μg)宫内节育器的研究回顾

目的总结我所对释放20μg左旋18甲基炔诺酮宫内节育器(LNGIUD)的研究,以阐明其作用机理、长效避孕效用和安全性。方法本文是我所发表的22篇临床报告和研究论文的综合分析。结果观察100例避孕效果,使用8年仅1例妊娠,续用率为52%,因医学原因取器为32.2%。观察10例随访1年有排卵周期者占44.8%,置器6年后,14例中有排卵周期者占78.5%;血清LNG水平有排卵者低,无排卵者高,提示闭经是高浓度LNG对子宫内膜的局部作用。形态学观察显示置器后子宫内膜增生受到抑制,内膜细胞核DNA含量明显下降,内膜细胞雌激素受体(ER)、孕激素受体(PR)表达受到抑制,内膜血管细胞因子VIII(FVIII)活性明显减低。提示月经的改变是LNGIUD对子宫内膜的局部作用。观察34例特发性月经过多的治疗达3年,月经血量(MBL)显著下降,血红蛋白(Hb)和铁蛋白明显增加。结论释放20μg的LNGIUD是一个安全、高效、长效、可逆的避孕方法。主要优点是降低MBL,可接受性高,适合于我国实际应用。尤其对月经过多和贫血的妇女,更应优先选择。     

Vascular endothelial growth factor induces nephrogenesis and vasculogenesis.

The expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the rat kidney was examined during ontogeny using Northern blot analysis and immunocytochemistry. In prevascular embryonic kidneys (embryonic day 14 [E14]), immunoreactive Flt-1 and Flk-1 were observed in isolated angioblasts, whereas VEGF was not detected. Angioblasts aligned forming cords before morphologically differentiating into endothelial cells. In late fetal kidneys (E19), immunoreactive VEGF was detected in glomerular epithelial and tubular cells, whereas Flt-1 and Flk-1 were expressed in contiguous endothelial cells. To determine whether VEGF induces endothelial cell differentiation and vascular development in the kidney, the effect of recombinant human VEGF (5 ng/ml) was examined on rat metanephric organ culture, a model known to recapitulate nephrogenesis in the absence of vessels. After 6 d in culture in serum-free, defined media, metanephric kidney growth and morphology were assessed. DNA content was higher in VEGF-treated explants (1.9 +/- 0.17 microg/kidney, n = 9) than in paired control explants (1.4 +/- 0.10 microg/kidney, n = 9) (P < 0.05). VEGF induced proliferation of tubular epithelial cells, as indicated by an increased number of tubules and tubular proliferating cell nuclear antigen-containing cells. VEGF induced upregulation of Flk-1 and Flt-1 expression, as assessed by Western blot analysis. Developing endothelial cells were identified and localized using immunocytochemistry and electron microscopy. Flt-1, Flk-1, and angiotensin-converting enzyme-containing cells were detected in VEGF-treated explants, whereas control explants were negative. These studies confirmed previous reports indicating that the expression of VEGF and its receptors is temporally and spatially associated with kidney vascularization and identified angioblasts expressing Flt-1 and Flk-1 in prevascular embryonic kidneys. The data indicate that VEGF expression is downregulated in standard culture conditions and that VEGF stimulates growth of embryonic kidney explants by expanding both endothelium and epithelium, resulting in vasculogenesis and enhanced tubulogenesis. These data suggest that VEGF plays a critical role in renal development by promoting endothelial cell differentiation, capillary formation, and proliferation of tubular epithelia.     

子宫内膜异位症和腺肌症患者子宫内膜雌激素受体的时空表达

目的　研究子宫内膜异位症和子宫腺肌症子宫内膜各种细胞中雌激素α和 β受体的表达模式 ,为探索子宫内膜异位症和子宫腺肌症的致病机理提供依据。　方法　 10 8例患有内膜异位症、腺肌症、两症并发组和对照组子宫内膜组织 ,常规光镜下按Noyes分期标准行形态学分期。采用免疫组织化学的方法观察不同月经周期时相子宫内膜腺上皮、基质和血管内皮细胞中雌激素受体ERα和ERβ的表达。　 结果　与对照组相比 ,ERα信号强度在各组相应的细胞类型、相应的时相无显著差异 ,但子宫内膜腺上皮细胞、基质细胞和血管内皮细胞中显示阳性信号的细胞比例增大 ,且腺上皮细胞质普遍出现ERα阳性信号。子宫内膜异位症和腺肌症的血管内皮细胞中ERα阳性细胞数显著增加。ERβ在各组的表达模式与对照组相比无明显差异 ,甚至略呈下降趋势。　结论　人子宫内膜中ERα为雌激素效应的主要受体亚型 ,表达ERα的腺上皮、基质和血管内皮细胞数量的增多以及腺上皮细胞质普遍出现ERα阳性信号可能与这两种疾病的发病密切相关 ;ERβ并不参与这一过程。     

Expression of vascular endothelial growth factor and its receptor Flk-1 in human neuroblastoma using in situ hybridization

Background/Purpose: Although angiogenic factors may play an important role in the biology of neuroblastoma, which frequently spreads hematogenously, the mechanism remains unclear. The authors studied tumor progression and invasion from the perspective of angiogenesis and sought to understand the features of this type of tumor. Methods: Thirty-one specimens were resected from patients with neuroblastoma and the expression of vascular endothelial growth factor (VEGF), and its receptor (Flk-1) was examined using immunohistochemistry. The authors looked for correlations among the expressions of VEGF and its receptor with various clinicopathologic factors. In addition, they examined the expression and location of VEGF and Flk-1 mRNA in 10 primary neuroblastoma using in situ hybridization. Results: Both in situ hybridization and immunohistochemistry showed the presence of VEGF expression within the neuroblastoma cells. We found VEGF mRNA in neuroblastoma cells but not vascular endothelial cells according to in situ hybridization. Further, Flk-1 mRNA was present both in neuroblastoma cells and vascular endothelial cells. The level of VEGF expression was higher in unfavorable histology, using the criteria of Shimada, than in favorable histology. Conclusion: The authors suggest that paracrine and autocrine systems are involved in the angiogenesis of neuroblastoma, and the expression of VEGF correlates with the prognosis in neuroblastoma.     

Expression of vascular endothelial growth factor and its two receptors in normal human endometrium

<正> Objectives:We try to demonstrate the expression of vascular endothelial growthfactor (VEGF) and its receptors,flt-1 and KDR,in normal human emdometrium duringthe menstrual cycle.Methods:Immunohistochemical method was used to observe the expression ofVEGF and its two receptors in emdometrium throughout the normal menstrual cyclemeanwhile the isoforms of VEGF were also detected by Western blot analysis.The en-dothelial cells of micro-vessels were marked with VIII factor antibody.Results:VEGF and its receptors existed in endometrial glandular,stromal and vas-cular endothelial cells of human endometrium.Their expressions were higher in the mid-secretory phase of menstrual cycle and highest at menstruation.VEGF_(121) and VEGF_(165)were the predominant isoforms in normal human endometrium.Conclusion:The expression of VEGF and its two receptors showed cycle-dependentin human endometrium,probably involved in embryonic implantation and endometrialproliferation and differentiation.     

Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease

BACKGROUND: Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in tissue remodelling and angiogenesis in COPD. METHODS: The cellular expression pattern of VEGF, Flt-1, and KDR/Flk-1 was examined by immunohistochemistry in central and peripheral lung tissues obtained from ex-smokers with COPD (forced expiratory volume in 1 second (FEV(1)) <75% predicted; n = 14) or without COPD (FEV(1) >85% predicted; n = 14). The immunohistochemical staining of each molecule was quantified using a visual scoring method with grades ranging from 0 (no) to 3 (intense). RESULTS: VEGF, Flt-1, and KDR/Flk-1 immunostaining was localised in vascular and airway smooth muscle (VSM and ASM) cells, bronchial, bronchiolar and alveolar epithelium, and macrophages. Pulmonary endothelial cells expressed Flt-1 and KDR/Flk-1 abundantly but not VEGF. Bronchial VEGF expression was higher in microvascular VSM cells and ASM cells of patients with COPD than in patients without COPD (1.7 and 1.6-fold, p<0.01, respectively). VEGF expression in intimal and medial VSM (1.7 and 1.3-fold, p<0.05) of peripheral pulmonary arteries associated with the bronchiolar airways was more intense in COPD, as was VEGF expression in the small pulmonary vessels in the alveolar region (1.5 and 1.7-fold, p<0.02). In patients with COPD, KDR/Flk-1 expression was enhanced in endothelial cells and in intimal and medial VSM (1.3, 1.9 and 1.5-fold, p<0.02) while endothelial Flt-1 expression was 1.7 times higher (p<0.03). VEGF expression was significantly increased in bronchiolar and alveolar epithelium as well as in bronchiolar macrophages (1.5-fold, p<0.001). The expression of VEGF in bronchial VSM and mucosal microvessels as well as bronchiolar epithelium was inversely correlated with FEV(1) (r<-0.45; p<0.01). CONCLUSIONS: VEGF and its receptors Flt-1 and KDR/Flk-1 may be involved in peripheral vascular and airway remodelling processes in an autocrine and/or paracrine manner. This system may also be associated with epithelial cell viability during airway wall remodelling in COPD.     

The effect of Chinese herbal medicine“heche assisted pregnancy recipe”on endometrial estrogen and progesterone receptor,proliferating cell nuclear antigen and vascular endothelial growth factor in the patients with infertility

<正> Objectives.To investigate the effect of Chinese herbal medicine"heche assisted preg-nancy recipe (HCAPR)"on estrogen receptor(ER),progesterone receptor (PR),pro-lifierating cell nuclear antigen(PCNA) and vascular endothelial growth factor (VEGF)in endometrium of infertile women.Methods.The S-P immunohistochemical assay was used to observe expression ofER,PR ,PCNA and VEGF in late proliferative phase before and after the HCAPR treat-ment.Results.After the treatment,the expression of ER,PR,PCNA and VEGF in nucleiof glandular epithelium and stromal cells was significantly stronger (all P<0.001) re-spectively than that before treatment,especially the expression of PCNA and VEGF.Conclusions..These results suggest that traditional Chinese medicine HCAPR oftonifying kidney and regulating menstruation increased the synthesis of ER,PR,PCNAand VEGF,which may promote normal growth and development of the endometrium ,improve the micro-environment of the endometrium,and enhance uterine receptivity.The evidence may provide theoretical basis for therapy infertility with Chinese herbalmedicine.     

着床期小鼠子宫内膜促血管生成素-2的表达

目的　检查促血管生成素- 2(Ang- 2)蛋白在小鼠着床期子宫内膜的分布及mRNA的表达,以探究Ang- 2基因表达在着床过程中的作用和生物学意义(OD)。　方法　取妊娠2、4、6和8 d的小鼠子宫内膜(蜕膜),运用免疫组织化学S P法和原位杂交技术,检测着床期子宫内膜中Ang- 2蛋白的表达及mRNA的转录水平。结合图像分析技术检测不同时期子宫内膜中Ang -2表达的平均光密度(OD)。　结果　结果显示,Ang 2特异性免疫反应产物在基质细胞及腔上皮细胞胞浆中表达,随着妊娠天数的增加,表达逐渐增强(P<0.01)。原位杂交显示,Ang- 2 mRNA自妊娠第2天起即表达于基质细胞和腺上皮;第4天血管壁胞浆中也出现阳性表达,且其表达强度在妊娠第 6、8 天时逐渐增加。平均 OD值具有显著性差异(P<0.01)。　结论　在小鼠妊娠过程中Ang- 2和Ang 2 mRNA在着床前小鼠子宫内膜中即开始表达,并随妊娠进程而表达增强,提示Ang 2基因在“胎 母”对话的信号传导过程中起调节作用。     

金氏痔疮膏对大鼠肛管静脉从血管内皮细胞生长因子表达的影响

目的：观察金氏痔疮膏对大鼠肛管静脉丛血管内皮细胞生长因子（VEGF）表达的影响，探讨其可能的治痔作用机制。方法：采用RT-PCR、ELISA法检测应用药物后大鼠肛管VEGF mRNA、VEGF表达的变化。结果：RT-PCR结果显示，大鼠肛管以表达VEGF 164 mRNA（563bp）为主；经金氏痔疮膏处理的大鼠肛管表达VEGF 164mRNA／β-acfin mRNA灰度值比值较对照组少；VEGF蛋白浓度较对照组低，且呈时间依赖性。结论：金氏痔疮膏在mRNA、蛋白水平均可抑制大鼠肛管血管内皮细胞生长因子表达。     

Expression of vascular endothelial growth factor and its receptors in rats with protein-overload nephrosis

Background. Based on the fact that vascular endothelial growth factor (VEGF) increases vascular permeability, it is speculated that VEGF might be involved in the development of proteinuria, although this remains unconfirmed. The production and site of action of VEGF remains unclear in nephrotic renal diseases. Methods. Non-radioactive in situ hybridization was performed to examine the expression of VEGF mRNA and its receptors, flt-1 and KDR/flk-1, in a rat model of nephrosis induced by intraperitoneal injection of bovine serum albumin (BSA). Saline injected rats were served as control animals. Results. Neither morphological changes nor deposition of immunoglobulin or complement were observed in our model. Proteinuria developed, reaching a maximum level in rats injected with BSA for 3 days, followed by persistent proteinuria until day 14. The expression of mRNA for VEGF and the two receptors was markedly upregulated in glomeruli of BSA-induced nephritis compared with the control group. VEGF mRNA was localized in glomerular cells, including cells in mesangium, visceral and parietal epithelial cells. In contrast, flt-1 mRNA and KDR/flk-1 mRNA were expressed on glomerular endothelial cells and cells in mesangium. The ratio of glomerular cells positive for VEGF mRNA and its receptors mRNA increased proportionately with the severity of proteinuria. Immunohistochemistry for ED-1 and proliferating cell nuclear antigen showed no significant increase in infiltrating macrophage or cellular proliferation. Conclusions. Our results suggest that altered glomerular expression of VEGF and its receptors is not associated with proliferation of endothelial cells, but rather with proteinuria in BSA-induced nephritis in rats, VEGF may play a different role in different renal diseases.