子宫腺肌病患者内膜组织中PTTG的表达及与MMP-2和TIMP-1的关系

目的:检测子宫腺肌病患者内膜组织中垂体肿瘤转化基因(PTTG)的表达,并分析其与基质金属蛋白-2(MMP-2)、基质金属蛋白酶组织抑制因子-1(TIMP-1)的柑关性.方法:采用免疫组化SP方法检测35例子宫腺肌病组、在位内膜组和24例非子宫腺肌病患者正常内膜组中PTTG、MMP-2及TIMP-1蛋白的表达水平.结果:①PTTG在子宫腺肌病组、在位内膜组和正常内膜组间的表达差异有高度统计学意义(P＜0.001),其中子宫腺肌病组和在位内膜组表达强度显著高于正常内膜组(P＜0.001),子宫腺肌病组与在位内膜组间差异无统计学意义(P＞0.05);②MMP-2在子宫腺肌病组和在位内膜组中的表达强度高于正常内膜组(P＜0.05);③TIMP-1在子宫腺肌病组中的表达比正常内膜组低,两组相比差异有高度统计学意义(P＜0.001);④PTTG与MMP-2的表达呈正相关,与TIMP-1的表达无相关性.结论:子宫腺肌病内膜中PTTG高表达,导致MMP-2表达上调,并可能影响TIMP-1的表达,从而使子宫内膜的增殖活性增强、侵袭力增高,致使子宫内膜向下浸润性生长,提示PTTG参与了子宫腺肌病的发生.     

神经细胞黏附因子在子宫腺肌病病灶中的表达及意义

目的:检测神经细胞黏附因子(NCAM)在子宫腺肌病在位内膜及异位内膜中的表达,探讨NCAM在子宫腺肌病发病中的作用。方法:采用免疫组化法检测40例子宫腺肌病标本在位内膜与异位内膜组织中NCAM的表达情况(分泌期与增生期各20期),并与20例正常子宫内膜标本进行比较。采用0~10级NRS疼痛评价量表对子宫腺肌病患者痛经程度进行评分,并与相应患者NCAM染色情况进行比较。结果:NCAM在40例子宫腺肌病在位内膜和异位内膜及19例正常内膜腺上皮中均有表达,1例正常内膜无表达,间质中无表达。异位内膜组织中NCAM表达明显高于在位内膜和正常对照组(P0.01)。在位内膜组织分泌期NCAM表达含量高于增生期(P0.05)。子宫腺肌病异位病灶NCAM表达与患者痛经程度呈正相关(r=0.84,P0.01)。结论:NCAM可能参与子宫腺肌病的发病过程,并参与子宫腺肌病痛经的发生发展,但具体分子机制尚需进一步研究。     

子宫内膜MMP-3表达和子宫腺肌病痛经的关系研究

目的研究基质金属蛋白酶（MMP～3）在子宫腺肌病中的表达,探讨其表达与子宫腺肌病的发生及痛经的相关性。方法应用免疫组化PV6000法检测45例子宫腺肌病在位内膜,36例异位内膜及28例对照组子宫内膜MMP-3的表达。结果MMP-3在子宫腺肌病异位内膜组中的表达显著高于子宫腺肌病在位内膜组及对照组（P〈O．05）。MMP-3在子宫腺肌病在位内膜增殖期和分泌期的表达强度比较,差异无统计学意义（P〉O．05）。MMP-3在子宫腺肌病异位内膜组中的表达与子宫腺肌病患者痛经呈正相关（r=O．557,P〈0．05）。结论MMP-3的异常表达可能与子宫腺肌病及其痛经的发生有关。     

Akt和NF-κB在子宫腺肌病中的表达及其意义

目的:研究Akt和NF-κB在子宫腺肌病病灶中的表达,探讨其在子宫腺肌病发生发展中的意义。方法:采用免疫组化SP法检测子宫腺肌病病灶(30例)、在位内膜(27例)、正常子宫内膜(20例)标本中Akt、P-Akt及NF-κB蛋白的表达并进行比较。结果:Akt、P-Akt蛋白在子宫腺肌病异位内膜的腺上皮细胞中的表达强度显著高于在位内膜(P<0.05)和正常子宫内膜(P<0.01),其在位内膜腺上皮细胞中的表达强度显著高于正常子宫内膜(P<0.01);间质细胞中Akt、P-Akt蛋白的表达,异位和在位内膜明显高于正常内膜,异位内膜和在位内膜中两者的表达无显著性差异。NF-κB蛋白表达于胞核和胞浆中,在腺上皮细胞中的表达,异位内膜显著高于在位内膜,在位内膜显著高于正常子宫内膜(P<0.05);间质细胞中,NF-κB蛋白的表达各组间无显著性差异。NF-κB与P-Akt在子宫腺肌病病灶、在位子宫内膜和正常子宫内膜中的表达呈正相关(r=0.626,P<0.01)。结论:NF-κB与Akt在子宫腺肌病病灶中呈高表达,其可能参与子宫腺肌病的发生与发展过程。     

乙酰肝素酶mRNA在子宫内膜异位症和子宫腺肌病中表达的研究

目的:检测子宫内膜异位症和子宫腺肌病在位及异位子宫内膜组织中乙酰肝素酶(heparanase,Hpa)mRNA的表达,探讨Hpa在子宫内膜异位症和子宫腺肌病发生发展中的作用及意义。方法:采用逆转录-聚合酶链反应(RT-PCR)技术检测50例子宫内膜异位症患者和42例子宫腺肌病患者的异位及在位内膜中Hpa mRNA的表达,并与30例妇女的正常子宫内膜进行比较。结果:(1)子宫内膜异位症组和子宫腺肌病组患者的异位及在位内膜中Hpa mRNA表达差异无显著性(P>0.05)。对照组正常子宫内膜中Hpa mRNA表达明显低于两组患者异位及在位内膜的阳性表达率(P<0.05);(2)Ⅰ~Ⅱ期子宫内膜异位症的异位及在位内膜中Hpa mRNA表达明显低于Ⅲ~Ⅳ期的异位与在位内膜表达(P<0.05)。结论:(1)Hpa与子宫内膜异位症和子宫腺肌病发病有关;(2)Hpa与子宫内膜异位症病情进展有关,是促进子宫内膜异位症病情进展的一个因素。     

E-cad、MMP-2在子宫腺肌病与子宫内膜癌中的表达及生物学行为相关性研究

目的:研究Ecad、MMP2在子宫腺肌病、子宫内膜癌中的表达,探讨其表达与子宫腺肌病发生及子宫腺肌病和子宫内膜癌生物学行为的相关性。方法:应用免疫组化SP染色法检测30例子宫腺肌病在位内膜、异位内膜,30例子宫内膜癌,16例对照组子宫内膜Ecad、MMP2的表达。结果:Ecad在子宫腺肌病在位内膜组和子宫内膜癌组中的表达显著低于对照组(P<0.05、P<0.01);Ecad在子宫腺肌病异位内膜组中的表达显著低于子宫腺肌病在位内膜组(P<0.01)。MMP2在子宫腺肌病异位内膜组中的表达显著高于子宫腺肌病在位内膜组及对照组(P<0.01、P<0.01);MMP2在子宫内膜癌组中的表达显著高于对照组(P<0.01)。Ecad、MMP2在子宫腺肌病异位内膜组与子宫内膜癌组中的表达差异均无显著性(P>0.05)。结论:Ecad、MMP2的异常表达可能与子宫腺肌病的发生有关;且可能与子宫腺肌病具有和子宫内膜癌相似的生物学行为有关。     

KISS-1及MMP-9在子宫内膜异位症患者异位及在位内膜的表达及意义

目的:探讨KISS-1及MMP-9在子宫内膜异位症患者在位及异位内膜组织的表达及意义。方法:用免疫组化方法检测46例患者异位子宫内膜组织及其中16例在位内膜组织和33例正常子宫内膜组织中KISS-1及MMP-9的表达情况。结果:KISS-1在子宫内膜异位症患者异位/在位内膜及正常子宫内膜组织中阳性表达率分别为30.43%、31.25%和63.64%,差异有统计学意义(P<0.05);MMP-9表达率分别为60.87%、56.25%和27.27%,差异有统计学意义(P<0.05);进一步比较KISS-1及MMP-9表达的阳性强度,3组间差异亦有统计学意义(P<0.01)。结论:KISS-1在子宫内膜异位症的表达降低,MMP-9的表达增高可能与内异症的侵袭有关。     

整合素连接激酶在子宫腺肌病中的表达及临床意义

目的:研究整合素连接激酶(ILK)在子宫腺肌症患者内膜及肌层组织中的表达及其临床意义。方法:选取2013年10月至2014年5月在山东大学齐鲁医院妇科行子宫切除术的53例患者,其中子宫腺肌病32例(腺肌病组),子宫肌瘤和宫颈上皮内瘤变21例(对照组)。采用免疫组化SP法检测ILK在对照组内膜、肌层,腺肌病组在位内膜、异位内膜及病灶肌层中的表达。采用Image-Pro Plus 6.0图像处理系统进行图像分析。结果:(1)腺肌病组在位内膜腺上皮及间质细胞中ILK表达均明显高于异位内膜及对照组正常内膜(P<0.05),且腺上皮细胞ILK的表达量与痛经程度呈明显正相关(r=0.571;P<0.05);异位内膜与对照组正常内膜比较,差异无统计学意义(P>0.05)。(2)腺肌病组内膜(在位及异位)腺上皮及间质细胞ILK的表达量均无周期性变化(P>0.05)。对照组内膜间质细胞ILK表达量增殖期较分泌期明显增加(P<0.05),腺上皮细胞ILK表达量无周期性变化(P>0.05)。(3)腺肌病组病灶肌层中ILK表达量明显高于对照组肌层(P<0.05),并与痛经程度及子宫大小呈正相关(r=0.362;P<0.05;r=0.555,P<0.05)。(4)腺肌病组病灶肌层增殖期的ILK表达水平明显高于分泌期(P<0.05),对照组肌层中ILK表达无周期性变化(P>0.05)。结论:子宫腺肌病患者在位内膜及病灶肌层组织中ILK表达显著增强,提示ILK在子宫腺肌病的发生发展中可能具有重要作用。     

MMP-2、TIMP-2在子宫内膜异位症组织中的表达及其意义

目的研究基质金属蛋白酶-2(MMP-2)及其抑制因子-2(TIMP-2)mRNA在子宫内膜异位症异位和在位内膜组织中的表达及临床意义。方法分别选取子宫内膜异位症异位内膜组织50例、在位内膜组织26例和对照组正常子宫内膜组织22例为研究对象,应用半定量逆转录聚合酶链反应技术(RT-PCR)检测MMP-2、TIMP-2mRNA的表达。结果(1)MMP-2mRNA在异位症异位内膜组织中相对表达量明显高于正常子宫内膜组织和在位内膜,差异均有显著性(P<0.01,P<0.01);TIMP-2mRNA在子宫内膜异位症异位内膜和在位内膜组织中均低表达,其相对表达量分别明显低于正常子宫内膜,差异均有显著性(P<0.01;P<0.01);(2)异位症异位内膜组织中MMP-2mRNA、TIMP-2的表达与r-AFS临床分期无关,差异无显著性(P>0.05)。结论异位和在位内膜组织中MMP-2高表达,TIMP-2低表达,使MMP-2与TIMP-2平衡失调,异位内膜组织侵袭降解ECM的能力增强,从而在子宫内膜异位症中的发生发展中起了重要作用。     

血管内皮生长因子在子宫腺肌病中的表达及意义

目的:研究血管内皮生长因子(VEGF)在子宫腺肌病中的组织定位和表达,以探讨VEGF与子宫腺肌病发生的关系。方法:用免疫组化染色法检测13例子宫腺肌病患者在位及异位子宫内膜中VEGF的表达。结果:在位和异位子宫内膜组织均有VEGF阳性染色。经计算机扫描图像处理,异位组织的腺上皮和间质VEGF表达高于在位组织的腺上皮及间质(P<0.05)。结论:高表达的VEGF可能与子宫腺肌病的发生和发展有关。     

基质金属蛋白酶-9及其组织抑制剂TIMP-3在子宫内膜异位症的表达

目的 :探讨基质金属蛋白酶 9(MMP 9)及其抑制剂TIMP 3在子宫内膜异位症发生发展中的作用。方法 :采用免疫组化链霉菌抗生物素蛋白 过氧化物酶染色法 (SP法 )检测 4 3例子宫内膜异位症的异位内膜和在位内膜中MMP 9、TIMP 3的表达 ,以 19例正常子宫内膜为对照组 ,并用银染法观察腺上皮基底膜的完整性。结果 :在异位内膜组织的腺上皮细胞MMP 9呈高表达状态 ,与子宫内膜异位症在位内膜和正常子宫内膜相比 ,差异有高度显著性 (P <0 .0 1)。子宫内膜异位症的在位内膜和异位内膜TIMP 3均呈低表达 ,与正常内膜相比 ,差异有高度显著性 (P <0 .0 1) ,异位内膜较在位内膜TIMP 3的表达降低 ,差异有显著性 (P <0 .0 5 )。子宫内膜腺上皮的基底膜银染结果显示 :MMP 9与TIMP 3的染色强度比值与基底膜的阳性率呈负相关 (P <0 .0 1)。MMP 9、TIMP 3的表达强度与子宫内膜异位症的严重程度无显著相关性。结论 :异位内膜组织中MMP 9过度表达 ,而TIMP 3的表达下降 ,导致MMP 9/TIMP 3的比例增高 ,使子宫内膜异位症患者的异位内膜更具侵袭性 ,在子宫内膜异位症的发生发展中起重要作用     

Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase,and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium

OBJECTIVE: To investigate expression of matrix metalloproteinase-2 (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in ectopic and eutopic endometrium from women with and without endometriosis throughout the menstrual cycle. DESIGN: Molecular studies in human tissue. SETTING: Reproductive immunology laboratory of a university medical center. PATIENT(S): Fifty-three premenopausal woman (23 with endometriosis and 30 without endometriosis) undergoing laparoscopic surgery. Endometrium and ectopic endometriosis tissue were obtained at the time of surgery. MAIN OUTCOME MEASURE(S): Messenger RNA and protein expression from eutopic and ectopic endometrium was analyzed by using quantitative competitive polymerase chain reaction, zymography, and Western blot assay. RESULT(S): Uterine endometrium from women with endometriosis expressed higher levels of MMP-2 and MT1-MMP and lower levels of TIMP-2 than did endometrium from normal women. CONCLUSION(S): Eutopic endometrium from patients with endometriosis may be more invasive and prone to peritoneal implantation because of greater expression of MMP-2 and MT1-MMP and lower expression of TIMP-2 messenger RNA, compared with endometrium from women without endometriosis. Thus, increased proteolytic activity may help to explain the invasive factors that result in endometriosis.     

基质金属蛋白酶MMP-2 MMP-9及其抑制因子TIMP-1TIMP-2在子宫内膜异位症中的表达及意义

目的　研究基质金属蛋白酶MMP 2、9和组织抑制因子TIMP 1、2在子宫内膜异位症中的表达及意义。方法　 2 0 0 0年 3月至 2 0 0 2年 4月应用免疫组化S P法检测卵巢巧克力囊肿 4 5例的异位内膜和其中 2 0例在位内膜 ,以及 2 2例正常子宫内膜中MMP 2、9及TIMP 1、2的表达。结果　异位内膜组织中MMP 2、9和TIMP 1、2的表达均显著高于在位内膜和正常内膜 (P <0 0 1)。在位内膜和正常子宫内膜组织细胞中的表达率比较 ,差异无显著性 (P >0 0 5 )。子宫内膜异位症组织中MMP 2、9的表达与侵袭程度正相关。TIMP 1、2的表达则与侵袭程度呈负相关。结论　MMP 2、9是检测子宫内膜异位症较好的分子标志 ,人工诱导TIMP 1、2或阻断MMP 2、9的表达可能抑制内异症的发生发展 ,有望成为子宫内膜异位症治疗新的辅助手段     

基质金属蛋白酶-9及基质金属蛋白酶组织抑制物-1表达失衡与宫颈癌局部肿瘤血管生成的关系

目的 :探讨基质金属蛋白酶 - 9(MMP 9)和基质金属蛋白酶组织抑制物 - 1(TIMP 1)在宫颈癌局部肿瘤血管生成中的作用。方法 :采用免疫组织化学SP法检测 75例早期宫颈癌 (ICC)、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮 (NCE)中MMP 9和TIMP 1的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )。结果 :从NCE组到CIN组再到ICC组 ,MMP 9的阳性表达率显著升高 (P <0 0 5 )而TIMP 1未见升高 (P >0 0 5 ) ,并且TIMP 1在ICC组的阳性表达率显著低于MMP 9(P <0 0 1)。MMP 9在ICC组中表达与MVD显著正相关 (r =0 2 87,P <0 0 5 ) ,而TIMP 1与MVD无显著相关性 (r=0 195 ,P >0 0 5 )。宫颈癌中MMP 9表达高于TIMP 1者 ,其MVD显著高于MMP 9表达低于TIMP 1者 (P <0 0 5 )。结论 :MMP 9和TIMP 1表达失衡可能在宫颈癌局部肿瘤血管生成中起重要作用 ,MMP 9表达增强而TIMP 1表达降低 ,其血管生成能力可能显著增强 ,但并非唯一决定因素。检测宫颈癌中MMP 9和TIMP 1表达对进一步了解宫颈癌局部血管生成情况有一定的应用价值。     

Matrix metalloproteinases and their tissue inhibitors in antegradely shed menstruum and peritoneal fluid

OBJECTIVE: To investigate the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in antegradely shed menstruum and peritoneal fluid. DESIGN: A cell biological and immunohistochemical study. SETTING: Tertiary care university medical center. INTERVENTION(s): Immunohistochemistry was performed on cryostat sections and cultures of menstrual endometrium. Zymography was used to characterize MMP activity in peritoneal fluid, in menstrual serum, and in conditioned medium. Western blot analysis was used to further identify the MMPs in these fluids. MAIN OUTCOME MEASURE(s): Staining of MMPs and TIMPs in cryostat sections and cultures and MMP expression and activity in peritoneal fluid and menstrual blood serum. RESULT(s): Strong staining for MMP-1 and MMP-3 was observed in stroma and for MMP-7 in epithelium. Matrix metalloproteinase-2 and MMP-9 were weakly expressed in stroma. Both TIMP-1 and TIMP-2 were expressed in menstrual endometrium. Menstrual serum showed a pattern of MMP activity on zymography different from peritoneal fluid. Western blot analysis showed the presence of MMP-7 and MMP-9 in menstrual serum. CONCLUSION(s): Antegradely shed menstrual endometrium expresses several MMPs and TIMPs, even after culturing for 24 hours. MMP activity in menstrual serum is different from and more intense than MMP activity in peritoneal fluid. These enzymes may be involved in the early invasion of menstrual endometrium into the extracellular matrix of the peritoneum.     

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 mRNA expression in ectopic and eutopic endometrium in women with endometriosis: a rationale for endometriotic invasiveness

OBJECTIVE: To investigate mRNA expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in ectopic endometriosis tissue and uterine endometrium from women with and without endometriosis throughout the menstrual cycle. DESIGN: Molecular studies in human tissue. SETTING: Department of Gynecology and Obstetrics, Reproductive Immunology Laboratory, Stanford University Medical Center. PATIENT(S): Fifty-three premenopausal woman (23 women with endometriosis and 30 women without endometriosis undergoing laparoscopic surgery). Endometrium and ectopic endometriosis tissue were obtained at the time of surgery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): mRNA expression from eutopic and ectopic endometrium was analyzed by quantitative, competitive PCR. RESULT(S): Both uterine endometrium and ectopic endometriotic tissue from women with endometriosis expressed significantly (P<.05) lower levels of TIMP-3 than endometrium from normal women. Also, ectopic endometrium expressed higher levels of MMP-9 and a higher ratio of MMP-9/TIMP-3 than eutopic endometrium from normal and endometriosis patients. CONCLUSION(S): These results suggest that ectopic and eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater MMP and less TIMP-3 mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one of the reasons for the invasive properties of the endometrium, resulting in the development of endometriosis.     

Matrix metalloproteinase-2 and -9 expression correlated with angiogenesis in human adenomyosis

BACKGROUND: Adenomyosis is an important cause of dysmenorrhea and infertility for women all over the world, however, the pathogenesis has not been completely elucidated. The purpose of the study was to investigate the role of matrix metalloproteinases (MMPs) and their relation to angiogenesis in human adenomyosis. METHODS: Adenomyotic endometrial specimens were removed by hysterectomy from 68 women with adenomyosis. The control group consisted of 26 normal endometrial specimens. Immunohistochemistry was used to demonstrate expression of MMP-2, -9, vascular endothelial growth factor (VEGF) and microvessel density (MVD). Staining intensity was analyzed by computerized image analysis system. RESULTS: In both eutopic and ectopic endometrium of adenomyosis, the expression of MMP-2, -9 as well as VEGF was significantly greater than in normal endometrium (p < 0.05). MVD was higher in ectopic endometrium than eutopic endometrium with or without adenomyosis (p < 0.05). In adenomyosis, a positive correlation was observed between VEGF expression and MMP-2 (p < 0.001, r = 0.583) as well as MMP-9 expression (p = 0.002,r = 0.490). A positive correlation was also found between MVD and MMP-2 (p < 0.001,r = 0.589) or MMP-9 expression (p < 0.001,r = 0.589). CONCLUSION: Our results indicate that the elevation of MMP-2, -9 expression may have an important role in the development of adenomyosis, probably through contributing to invasion of endometrial tissues into the myometrium and angiogenesis in adenomyotic implants.     

Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs

OBJECTIVE: To establish the effect of hormone replacement therapy (HRT) on the expression of matrix metalloproteinase 9 (MMP-9) and the tissue inhibitor of MMPs, TIMP-1, in the endometrium of postmenopausal and perimenopausal women. DESIGN: Prospective observational study. SETTING: United Kingdom teaching hospital. PATIENT(S): Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT. INTERVENTION(S): Prospective record of bleeding patterns and endometrial biopsy. MAIN OUTCOME MEASURE(S): Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression. RESULT(S): MMP-9 and TIMP-1 are expressed in benign postmenopausal endometrium. Expression of both molecules is reduced in HRT recipients compared with non-HRT recipients. CONCLUSION(S): Exposure to HRT appears to alter endometrial expression of MMP-9 and TIMP-1 and also the local balance between these molecules. This alteration may promote breakdown of the endometrial extracellular matrix and blood vessels and hence bleeding.