Tawfik O W, Dey S K
Department of Obstetrics and Gynecology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103.
Prostaglandins. 1988 Mar;35(3):379-86. doi: 10.1016/0090-6980(88)90129-3.
Inhibitors of leukotrienes were utilized to investigate the role of leukotrienes (LTs) in the induction of decidualization in the rat. Alzet osmotic minipumps, filled with either FPL 55712 (FPL, a specific antagonist of peptidoleukotrienes), nordihydroguaiaretic acid (NDGA, an inhibitor of LT synthesis) or in combination with leukotriene C4 (LTC4) and/or prostaglandin E2 (PGE2), were instilled at the ovarian end of uterine horns of day 5 pseudopregnant rats. Intraluminal infusion of FPL or NDGA, for 4 days, induced a dose dependent decrease in the uterine wet weights when compared to that induced by the infusion of their corresponding vehicles (1 microliter/h). Furthermore, simultaneous infusion of LTC4 (10 ng/h) with different doses of FPL (1, 0.5, or 0.25 microgram/h) produced an increase in uterine weights as compared to that produced by FPL alone. Maximum response, however, was noted when LTC4 (10 ng/h) was infused with FPL at a rate of 0.5 microgram/h. The infusion of LTC4 (10 ng/h) or PGE2 (1 microgram/h) with NDGA, at 1 and 5 micrograms/h, could not overcome its inhibitory effect on decidualization. On the contrary, a combination of LTC4 (10 ng/h) and PGE2 (1 microgram/h) along with NDGA (5 micrograms/h) significantly increased the uterine weight to a level that was comparable to that induced by the infusion of the vehicle. To determine if the synthesis of PGs and LTs was inhibited by NDGA, one uterine horn was infused with NDGA (5 micrograms/h) and the other horn with the vehicle. The intrauterine infusion of NDGA for 24 h inhibited the release of PGE2, PGF2 alpha, LTC4 and LTB4 as compared to those released by the vehicle-infused horns. These data suggest that both PGs and LTs are required for the induction and progression of decidualization.
利用白三烯抑制剂来研究白三烯（LTs）在大鼠蜕膜化诱导过程中的作用。将充满FPL 55712（FPL，一种肽白三烯的特异性拮抗剂）、去甲二氢愈创木酸（NDGA，一种LT合成抑制剂）或与白三烯C4（LTC4）和/或前列腺素E2（PGE2）联合的Alzet渗透微型泵，注入第5天假孕大鼠子宫角的卵巢端。与注入相应赋形剂（1微升/小时）相比，腔内注入FPL或NDGA 4天可导致子宫湿重呈剂量依赖性降低。此外，与单独注入FPL相比，同时注入LTC4（10纳克/小时）和不同剂量的FPL（1、0.5或0.25微克/小时）可使子宫重量增加。然而，当LTC4（10纳克/小时）与FPL以0.5微克/小时的速率注入时，观察到最大反应。以1和5微克/小时的速率将LTC4（10纳克/小时）或PGE2（1微克/小时）与NDGA一起注入，不能克服其对蜕膜化的抑制作用。相反，LTC4（10纳克/小时）和PGE2（1微克/小时）与NDGA（5微克/小时）的组合可使子宫重量显著增加至与注入赋形剂诱导的水平相当。为了确定PGs和LTs的合成是否被NDGA抑制，一个子宫角注入NDGA（5微克/小时），另一个子宫角注入赋形剂。与注入赋形剂的子宫角相比，子宫内注入NDGA 24小时可抑制PGE2、PGF2α、LTC4和LTB4的释放。这些数据表明，PGs和LTs都是蜕膜化诱导和进展所必需的。
