前列腺素E_2，环氧化酶-2在功能失调性子宫出血及子宫内膜癌患者血浆中的表达及意义
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摘要
目的检测功能失调性子宫出血(Dysfunctional uterine bleeding,DUB)和子宫内膜癌(Endometrial cancer, EC)患者外周血浆中前列腺素E2(prostaglandin-E2, PGE2)与环氧化酶-2(Cyclooxygenase-2, COX-2)的表达水平,探讨其在功能失调性子宫出血及子宫内膜癌疾病发生发展中的价值。
方法采集40例35-60岁DUB患者,20例EC患者,20例正常月经妇女空腹血浆并收集其年龄、体重、月经情况等基本资料,采用酶联免疫吸附试验(ELISA)测定各组样本血浆中的PGE2及COX-2的含量,操作严格按照试剂盒说明进行,终止反应后在450nm处读取吸光度值,以标准品各孔吸光度值为纵坐标,以浓度为横坐标,用统计软件绘制出标准曲线并计算出直线方程,然后根据样品吸光度值计算出样本中对应的PGE2及COX-2浓度。
结果各组纳入人员在年龄,身高,体重以及正常月经情况差异无统计学意义,但DUB组及EC组近期的阴道流血时间以及出血量均比正常组高(P<0.001)；DUB患者外周循环中COX-2较正常月经妇女明显升高,但PGE2与正常组差异并没有统计学意义。EC患者COX-2及PGE浓度较正常月经妇女明显升高(P<0.001)。
结论此研究发现DUB患者外周血浆中COX-2较对照组明显升高(P<0.001),PGE2并没有明显升高,而COX-2作为PGE2合成的关键酶,其升高可能与子宫内膜血管的修复与重建有关,因DUB患者外周血.浆中PGE2表达和对照组之间无无统计学意义,也不能说明其透过血脑屏障诱发下丘脑促性腺激素的合成和分泌,因此我们认为在DUB的发生发展中没有起到明显作用。COX-2在DUB患者及EC患者的外周血中表达均出现升高,不排除EC患者外周循环中COX-2促进PGE2的表达,使得下丘脑GnRH的释放受到影响进而影响EC的发展,总之COX-2及PGE2在EC的发生及发展中的意义有待进一步深入的研究。
Objective:To study the expression and clinical significance of prostaglandin-E2(PGE2)and cyclooxygenase-2(COX-2) in the Plasma of Patients with dysfunctional uterine bleeding or endometrial carcinoma.
Method:We had randomly selected20normal women as control group,40dysfunctional uterine bleeding (DUB) patients and20endometrial cancer (EC) patients were randomly selected as experimental group between the years of2010and2012. Basic information was collected by machine and registrars inquiring in person. The level of PGE2and COX-2in the plasma of patients in different groups was detected by enzyme linked immune-sorbent assay (ELISA). All the steps are in accordance with the instructions of kits. Optical density was read at450nm after the reaction terminated. Optical density values of standard product for longitudinal coordinates, concentration values of standard product for the abscissa, then draw the standard curve and calculate the equation of the straight line with statistical software software. Finally, to identify corresponding PGE2and COX-2content.
Results:The basic information such as age, height, weight and the normal menstrual condition have no statistically significant in these three groups. But the recent vaginal bleeding time and amount of bleeding in the DUB group and the EC group are higher than those of normal group (P<0.001). The expression of COX-2in DUB group and EC group was significantly higher than the control one (P<0.001).The expression of PGE2in the20endometrial cancer patients was much higher than the control (P <0.001).
Conclusion:The study found that PGE2in peripheral blood plasma of DUB patients had no obvious rise, which can also not induce the synthesis and secretion of hypothalamus gonadotropin. In peripheral blood plasma, PGE2didn't play a leading role in the happening and developing of DUB. The quantity of circulating COX-2and PGE2in EC patients increased significantly (P<0.001) compared to the normal menstrual women. COX-2in the DUB and EC happening and developing needs further study.
方法采集40例35-60岁DUB患者,20例EC患者,20例正常月经妇女空腹血浆并收集其年龄、体重、月经情况等基本资料,采用酶联免疫吸附试验(ELISA)测定各组样本血浆中的PGE2及COX-2的含量,操作严格按照试剂盒说明进行,终止反应后在450nm处读取吸光度值,以标准品各孔吸光度值为纵坐标,以浓度为横坐标,用统计软件绘制出标准曲线并计算出直线方程,然后根据样品吸光度值计算出样本中对应的PGE2及COX-2浓度。
结果各组纳入人员在年龄,身高,体重以及正常月经情况差异无统计学意义,但DUB组及EC组近期的阴道流血时间以及出血量均比正常组高(P<0.001)；DUB患者外周循环中COX-2较正常月经妇女明显升高,但PGE2与正常组差异并没有统计学意义。EC患者COX-2及PGE浓度较正常月经妇女明显升高(P<0.001)。
结论此研究发现DUB患者外周血浆中COX-2较对照组明显升高(P<0.001),PGE2并没有明显升高,而COX-2作为PGE2合成的关键酶,其升高可能与子宫内膜血管的修复与重建有关,因DUB患者外周血.浆中PGE2表达和对照组之间无无统计学意义,也不能说明其透过血脑屏障诱发下丘脑促性腺激素的合成和分泌,因此我们认为在DUB的发生发展中没有起到明显作用。COX-2在DUB患者及EC患者的外周血中表达均出现升高,不排除EC患者外周循环中COX-2促进PGE2的表达,使得下丘脑GnRH的释放受到影响进而影响EC的发展,总之COX-2及PGE2在EC的发生及发展中的意义有待进一步深入的研究。
Objective:To study the expression and clinical significance of prostaglandin-E2(PGE2)and cyclooxygenase-2(COX-2) in the Plasma of Patients with dysfunctional uterine bleeding or endometrial carcinoma.
Method:We had randomly selected20normal women as control group,40dysfunctional uterine bleeding (DUB) patients and20endometrial cancer (EC) patients were randomly selected as experimental group between the years of2010and2012. Basic information was collected by machine and registrars inquiring in person. The level of PGE2and COX-2in the plasma of patients in different groups was detected by enzyme linked immune-sorbent assay (ELISA). All the steps are in accordance with the instructions of kits. Optical density was read at450nm after the reaction terminated. Optical density values of standard product for longitudinal coordinates, concentration values of standard product for the abscissa, then draw the standard curve and calculate the equation of the straight line with statistical software software. Finally, to identify corresponding PGE2and COX-2content.
Results:The basic information such as age, height, weight and the normal menstrual condition have no statistically significant in these three groups. But the recent vaginal bleeding time and amount of bleeding in the DUB group and the EC group are higher than those of normal group (P<0.001). The expression of COX-2in DUB group and EC group was significantly higher than the control one (P<0.001).The expression of PGE2in the20endometrial cancer patients was much higher than the control (P <0.001).
Conclusion:The study found that PGE2in peripheral blood plasma of DUB patients had no obvious rise, which can also not induce the synthesis and secretion of hypothalamus gonadotropin. In peripheral blood plasma, PGE2didn't play a leading role in the happening and developing of DUB. The quantity of circulating COX-2and PGE2in EC patients increased significantly (P<0.001) compared to the normal menstrual women. COX-2in the DUB and EC happening and developing needs further study.
引文
[1]Munro MG, Broder M, Critchley HO, et al. An international response to questions about terminologies, investigation, and management of abnormal uterine bleeding:use of an electronic audience response system[J]. Semin Reprod Med,2011.29(5):436-445.
[2]Tu X, Huang G,Tan S. Chinese Herbal Medicine for Dysfunctional Uterine Bleeding:a Meta-analysis[J]. Evid Based Complement Alternat Med,2009,6(1):99-105.
[3]Maness DL, Reddy A, Harraway-smith CL, et al. How best to manage dysfunctional uterine bleeding[J]. J Fam Pract,2010.59(8):449-458.
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[7]李继俊.妇产科内分泌治疗学[M].第一版.北京：人民军医出版社,2005：129-133.
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[12]Jensen DV, AnderseN KB,Wagner G. Prostaglandins in the menstrual cycle of women. A review[J]. Dan Med Bull,1987.34(3):178-182.
[13]Maroni D,Davis JS. TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum[J]. J Cell Sci,2011.124(Pt 14):2501-2510.
[14]Mondal M, Schilling B, Folger J, et al. Deciphering the luteal transcriptome:potential mechanisms mediating stage-specific luteolytic response of the corpus luteum to prostaglandin F(2)alpha[J]. Physiol Genomics,2011.43(8):447-456.
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[20]Makarainen L,Ylikorkala O. Primary and myoma-associated menorrhagia:role of prostaglandins and effects of ibuprofen[J]. Br J Obstet Gynaecol,1986.93(9):974-978.
[21]薛凤霞,李卉,焦书竹.雌激素依赖型与非雌激素依赖型子宫内膜癌临床病理特征的研究[J].中国肿瘤临床,2000.(09)：42-45.
[22]徐澈,赖爱鸾.子宫内膜癌的分子病理学机制与研究进展[J].现代妇产科进展,2010.(02)：140-142.
[23]刘曼华,陶潜,郑艳莉,等Surviving雌激素受体、孕激素受体在子宫内膜癌中表达的意义[J].南通大学学报(医学版),2007.(05)：346-348.
[24]Haring J, Skrzypczak M, Stegerer A, et al. Estrogen receptor beta transcript variants associate with oncogene expression in endometrial cancer[J]. International journal of molecular medicine,2012.29(6):1127-36.
[25]Zhang Z, Zhou D, Lai Y, et al. Estrogen induces endometrial cancer cell proliferation and invasion by regulating the fat mass and obesity-associated gene via PI3K/AKT and MAPK signaling pathways[J]. Cancer Letters,2012,319(1):89-97.
[26]王敏,马志红,史春雪.子宫内膜癌组织COX-2和VEGF及KDR蛋白表达临床意义的探讨[J].中华肿瘤防治杂志,2009.(22)：1782-1785.
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[1]Munro MG, Broder M, Critchley HO, et al. An international response to questions about terminologies, investigation, and management of abnormal uterine bleeding:use of an electronic audience response system[J]. Semin Reprod Med,2011,29(5):436-445.
[2]Tu X, Huang G, Tan S. Chinese herbal medicine for dysfunctional uterine bleeding:a meta-analysis[J]. Evid Based Complement Alternat Med,2009,6(1):99-105.
[3]Casablanca Y. Management of dysfunctional uterine bleeding[J]. Obstet Gynecol Clin North Am,2008,35(2):219-234.
[4]Maness DL, Reddy A, Harraway-smith CL, et al. How best to manage dysfunctional uterine bleeding[J]. J Fam Pract,2010,59(8):449-458.
[5]Bresson E, Boucher-Kovalik S, Chapdelaine P, et al. The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium[J]. J Clin Endocrinol Metab, 2011,96(1):210-219.
[6]Maybin JA, Hirani N, Jabbour HN, et al. Novel roles for hypoxia and prostaglandin E2 in the regulation of IL-8 during endometrial repair[J]. Am J Pathol,2011,178(3):1245-1256.
[7]Maybin JA, Hirani N, Brown P, et al. The regulation of vascular endothelial growth factor by hypoxia and prostaglandin F(2)alpha during human endometrial repair[J]. J Clin Endocrinol Metab,2011,96(8):2475-2483.
[8]李继俊.妇产科内分泌治疗学[M].第一版.北京：人民军医出版社,2005：129-133.
[9]Rivest S. Interactions between the immune and neuroendocrine systems[J], Prog Brain Res, 2010,181:43-53.
[10]Mori d, Ogino N, Yonezawa T, et al. Anti-ovulatory effects of RU486 and trilostane involve impaired cyclooxygenase-2 expression and mitotic activity of follicular granulosa cells in rats[J]. Prostaglandins Other Lipid Mediat,2011,94(3-4):118-123.
[11]Abe T, Toida D, Satoh H, et al. An early single dose of progesterone agonist attenuates endogenous progesterone surge and reduces ovulation rate in immature rat model of induced ovulation[J].Steroids,2011,76(10-11):1116-1125.
[12]Bridges PJ,Fortune JE. Regulation, action and transport of prostaglandins during the periovulatory period in cattle[J]. Mol Cell Endocrinol,2007,263(1-2):1-9.
[13]Jensen DV AK, Wagner G. Prostaglandins in the menstrual cycle of women. A review.[J]. Dan Med Bull,1987,34(4):4.
[14]Maroni D,Davis JS. TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum[J]. J Cell Sci,2011,124(Pt 14):2501-2510.
[15]Mondal M, Schilling B, Folger J, et al. Deciphering the luteal transcriptome:potential mechanisms mediating stage-specific luteolytic response of the corpus luteum to prostaglandin F(2)alpha[J]. Physiol Genomics,2011,43(8):447-456.
[16]Lindner HR, Zor U, Kohen F, et al. Significance of prostaglandins in the regulation of cyclic events in the ovaryand uterus[J]. Adv Prostaglandin Thromboxane Res,1980,8:19.
[17]Maybin JA, Battersby S, Hirani N, et al. The expression and regulation of adrenomedullin in the human endometrium:a candidate for endometrial repair[J]. Endocrinology,2011, 152(7):2845-2856.
[18]Smith OP, Jabbour HN,Critchley HO.Cyclooxygenase enzyme expression and E series prostaglandin receptor signalling are enhanced in heavy menstruation[J]. Hum Reprod,2007, 22(5):1450-1456.
[19]Smith SK AM, kelly RW, Baird DT. A role for prostacyclin (PGi2) in excessive menstrual bleeding[J]. Lancet,1981,1(8219):3.
[20]Makarainen L,Ylikorkala O. Primary and myoma-associated menorrhagia:role of prostaglandins and effects of ibuprofen[J]. BJOG:An International Journal of Obstetrics & Gynaecology,1986,93(9):974-978.
[2]Tu X, Huang G,Tan S. Chinese Herbal Medicine for Dysfunctional Uterine Bleeding:a Meta-analysis[J]. Evid Based Complement Alternat Med,2009,6(1):99-105.
[3]Maness DL, Reddy A, Harraway-smith CL, et al. How best to manage dysfunctional uterine bleeding[J]. J Fam Pract,2010.59(8):449-458.
[4]Casablanca Y. Management of dysfunctional uterine bleeding[J]. Obstet Gynecol Clin North Am,2008.35(2):219-34, viii.
[5]肖伟忠.环氧化酶调制血管功能的研究进展[J].医学综述,2003.(05)：307-308.
[6]Smith OP, Jabbour HN,Critchley HO. Cyclooxygenase enzyme expression and E series prostaglandin receptor signalling are enhanced in heavy menstruation[J]. Hum Reprod, 2007.22(5):1450-1456.
[7]李继俊.妇产科内分泌治疗学[M].第一版.北京：人民军医出版社,2005：129-133.
[8]Rivest S. Interactions between the immune and neuroendocrine systems[J]. Prog Brain Res, 2010,181:43-53.
[9]Mori D, Ogino N, Yonezawa T, et al. Anti-ovulatory effects of RU486 and trilostane involve impaired cyclooxygenase-2 expression and mitotic activity of follicular granulosa cells in rats[J]. Prostaglandins Other Lipid Mediat,2011.94(3-4):118-123.
[10]Abe T, Toida D, Satoh H, et al. An early single dose of progesterone agonist attenuates endogenous progesterone surge and reduces ovulation rate in immature rat model of induced ovulation[J]. Steroids,2011.76(10-11):1116-1125.
[11]Bridges PJ,Fortune JE. Regulation, action and transport of prostaglandins during the periovulatory period in cattle[J]. Mol Cell Endocrinol,2007,263(1-2):1-9.
[12]Jensen DV, AnderseN KB,Wagner G. Prostaglandins in the menstrual cycle of women. A review[J]. Dan Med Bull,1987.34(3):178-182.
[13]Maroni D,Davis JS. TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum[J]. J Cell Sci,2011.124(Pt 14):2501-2510.
[14]Mondal M, Schilling B, Folger J, et al. Deciphering the luteal transcriptome:potential mechanisms mediating stage-specific luteolytic response of the corpus luteum to prostaglandin F(2)alpha[J]. Physiol Genomics,2011.43(8):447-456.
[15]Lindner HR, Zor U, Kohen F, et al. Significance of prostaglandins in the regulation of cyclic events in the ovary and uterus[J]. Adv Prostaglandin Thromboxane Res,1980. 8:1371-1390.
[16]Maybin JA, Battersby S, Hirani N, et al. The expression and regulation of adrenomedullin in the human endometrium:a candidate for endometrial repair[J]. Endocrinology,2011. 152(7):2845-2856.
[17]Maybin JA, Hirani N, Brown P, et al. The regulation of vascular endothelial growth factor by hypoxia and prostaglandin F(2)alpha during human endometrial repair[J]. J Clin Endocrinol Metab,2011.96(8):2475-2483.
[18]Maybin JA, Hirani N, Jabbour HN, et al. Novel roles for hypoxia and prostaglandin E2 in the regulation of IL-8 during endometrial repair[J]. Am J Pathol,2011.178(3):1245-1256.
[19]Smith SK, Abel MH, Kelly RW, et al. Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding[J]. Br J Obstet Gynaecol,1981. 88(4):434-442.
[20]Makarainen L,Ylikorkala O. Primary and myoma-associated menorrhagia:role of prostaglandins and effects of ibuprofen[J]. Br J Obstet Gynaecol,1986.93(9):974-978.
[21]薛凤霞,李卉,焦书竹.雌激素依赖型与非雌激素依赖型子宫内膜癌临床病理特征的研究[J].中国肿瘤临床,2000.(09)：42-45.
[22]徐澈,赖爱鸾.子宫内膜癌的分子病理学机制与研究进展[J].现代妇产科进展,2010.(02)：140-142.
[23]刘曼华,陶潜,郑艳莉,等Surviving雌激素受体、孕激素受体在子宫内膜癌中表达的意义[J].南通大学学报(医学版),2007.(05)：346-348.
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