Sharpe-Timms K L, Zimmer R L, Jolliff W J, Wright J A, Nothnick W B, Curry T E
University of Missouri, Columbia 65212, USA.
Fertil Steril. 1998 May;69(5):916-23. doi: 10.1016/s0015-0282(98)00032-6.
To evaluate the effects of a gonadotropin-releasing hormone agonist (GnRH-a) on plasminogen activator (PA), matrix metalloproteinase (MMP), plasminogen activator inhibitor (PAI) and matrix metalloproteinase inhibitor (MMPI) activities in peritoneal fluid relative to GnRH-a-induced reduction of adhesion formation.
Continuation of prospective randomized study using surgical models for adhesion formation.
Department of Obstetrics and Gynecology research laboratory at the University of Missouri School of Medicine.
PATIENT(S): Forty reproductively cycling female Sprague-Dawley rats.
INTERVENTION(S): Female rats were injected with depot GnRH-a or diluent and randomly assigned to adhesion and endometriosis surgeries. Peritoneal fluid was collected prior to (time 1) and 7 weeks from (time 2) initial surgery.
MAIN OUTCOME MEASURE(S): Peritoneal fluid was analyzed for PA, PAI, MMP, and MMPI activities.
RESULT(S): At time 1, MMP and MMPI activities were similar in all rats; however, PA and PAI activities were less in rats pretreated with GnRH-a than with diluent. Between time 1 and time 2, GnRH-a-treated rats showed an increase in PAI and MMPI activities without significant changes in PA or MMP activities, whereas rats receiving diluent showed a significant increase in PAI and MMP activities but no significant changes in PA or MMPI activities. At time 2, rats receiving GnRH-a had less PA and MMP activities than those receiving diluent. Adhesion scores showed a positive correlation with MMP activity.
CONCLUSION(S): In the absence of GnRH-a therapy, surgical tissue manipulation increased peritoneal fluid MMP and PAI activity. Gonadotropin-releasing hormone agonist therapy decreased PA and MMP activities and also increased PAI and MMPI activities. This GnRH-a-induced shift to a less invasive phenotype may alter fibrinolysis and extracellular matrix remodeling and thereby play a role in the mechanism of GnRH-a-induced reduction in adhesion formation.
评估促性腺激素释放激素激动剂（GnRH-a）对腹腔液中纤溶酶原激活物（PA）、基质金属蛋白酶（MMP）、纤溶酶原激活物抑制剂（PAI）和基质金属蛋白酶抑制剂（MMPI）活性的影响，以及其与GnRH-a诱导的粘连形成减少之间的关系。
采用手术模型形成粘连的前瞻性随机研究的延续。
密苏里大学医学院妇产科研究实验室。
40只处于生殖周期的雌性斯普拉格-道利大鼠。
给雌性大鼠注射长效GnRH-a或稀释剂，并随机分配接受粘连和子宫内膜异位症手术。在初次手术前（时间1）和初次手术后7周（时间2）收集腹腔液。
分析腹腔液中的PA、PAI、MMP和MMPI活性。
在时间1时，所有大鼠的MMP和MMPI活性相似；然而，用GnRH-a预处理的大鼠的PA和PAI活性低于用稀释剂预处理的大鼠。在时间1和时间2之间，接受GnRH-a治疗的大鼠的PAI和MMPI活性增加，而PA或MMP活性无显著变化，而接受稀释剂的大鼠的PAI和MMP活性显著增加，但PA或MMPI活性无显著变化。在时间2时，接受GnRH-a的大鼠的PA和MMP活性低于接受稀释剂的大鼠。粘连评分与MMP活性呈正相关。
在未进行GnRH-a治疗的情况下，手术组织操作会增加腹腔液中MMP和PAI活性。促性腺激素释放激素激动剂治疗可降低PA和MMP活性，并增加PAI和MMPI活性。这种GnRH-a诱导的向侵袭性较小表型的转变可能会改变纤维蛋白溶解和细胞外基质重塑，从而在GnRH-a诱导粘连形成减少的机制中发挥作用。
