Mechanisms of lipopotysaccharide-induced changes in effects of contractile agonists on pregnant rat myometrium
Mechanisms of lipopotysaccharide-induced changes in effects of contractile agonists on pregnant rat myometrium
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DOI：
10.1016/s0002-9378(03)00949-9
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发表时间：
2004-02-01
影响因子：
9.8
通讯作者：
Prakash, VR
中科院分区：
文献类型：
--
作者：
Ross, RG;Sathishkumar, K;Prakash, VR
目的：本研究旨在探讨脂多糖（LPS）诱导的妊娠大鼠子宫收缩力增强的机制。研究设计：Wistar大鼠在妊娠第17天子宫内给予LPS（50 μ g）或生理盐水溶液（0.05 mL）。第19天处死动物，分离子宫进行等长收缩记录、Ca-45（++）内流测定和质膜Na+-K+-ATP酶测定。与对照组相比，大鼠的自发节律性收缩幅度显着增加。在用LPS处理的大鼠中还观察到子宫条对激动剂如催产素、5-羟色胺（5-HT）和BAY K8644的敏感性增强。环氧化酶-2抑制剂尼美舒利（10 μ mol/L）对LPS诱导的自发节律性收缩的增加无明显影响。另一方面，尼美舒利减弱LPS诱导的子宫条对催产素的敏感性增加。尼美舒利显着抑制5-HT诱导的子宫收缩在对照组和LPS治疗的大鼠。然而，增强的敏感性，子宫条5-HT是明显的，即使在尼美舒利的存在下，用LPS治疗的大鼠。在基础状态和高K+（80 mmol/L）和5-HT（1 mumol/L）刺激下，LPS组子宫肌条对硝苯地平敏感的Ca-45（++）-内流均高于对照组。与对照组相比，LPS处理引起子宫质膜Na+-K+-ATP酶活性的显著抑制。结论：LPS可能通过释放内源性β-雌二醇和增加L-型Ca++通道Ca+内流而增强孕鼠子宫收缩力。LPS对钠泵的抑制可能是其增强子宫兴奋性的另一机制。(C)2004年爱思唯尔公司All rights reserved.
Objective: The study was undertaken to investigate the mechanisms underlying enhanced uterine contractility induced by lipopolysaccharide (LPS) in pregnant rats.Study design: Wistar rats were administered intrauterine either LPS (50 mug) or normal saline solution (0.05 mL) on day 17 of gestation. On day 19, the animals were killed and uterus was isolated for isometric recording, Ca-45(++) influx measurement, and determination of plasma membrane Na+-K+-ATPase.Results: Uterine strips, taken from LPS-treated. rats, displayed a marked increase in amplitude of spontaneous rhythmic contractions compared with controls. Enhancement in the sensitivity of uterine strips to agonists such as oxytocin, 5-hydroxytryptamine (5-HT), and BAY K8644 was also observed in rats treated with LPS. Cyclo-oxygenase-2 inhibitor, nimesulide (10 mumol/L) had no significant effect on the LPS-induced increase in spontaneous rhythmic contractions. On the other hand, nimesulide attenuated the increased sensitivity of uterine strips to oxytocin induced by LPS. Nimesulide significantly inhibited 5-HT-induced uterine contractions in both control and LPS-treated rats. However, the enhanced sensitivity of uterine strips to 5-HT was evident even in the presence of nimesulide in rats treated with LPS. Nifedipine-sensitive Ca-45(++)-influx into uterine strips both in the basal state as well as those stimulated by high K+ (80 mmol/L) and 5-HT (1 mumol/L) was greater in LPS-treated group compared with the controls. LPS treatment caused a marked inhibition in the Na+-K+-ATPase activity of the uterine plasma membrane compared with controls. LPS had no effect on plasma 17beta-estradiol levels.Conclusion: LPS appears to increase uterine contractility of pregnant rats both through the release of endogenous prostaglandins and increased influx of Ca++ through L-type Ca++ channels. Inhibition of sodium pump by LPS may be an additional mechanism in augmentation of uterine excitability. (C) 2004 Elsevier Inc. All rights reserved.