Pons L, Droy-Lefaix M T, Braquet P, Bueno L
Department of Pharmacology-Toxicology, Institut National de la Recherche Agronomique, Toulouse, France.
Gastroenterology. 1991 Apr;100(4):946-53. doi: 10.1016/0016-5085(91)90268-p.
The effects of IV administration of Escherichia coli endotoxin on intestinal myoelectric activity was investigated in conscious fasted rats chronically implanted with nichrome electrodes in the duodenojejunum. These effects were compared with those of platelet-activating factor and were evaluated in animals pretreated with a specific platelet-activating factor antagonist, BN 52021, indomethacin, a selective prostaglandin E2 antagonist, SC 19220, and several free radical scavengers. Intravenous administration of endotoxin (E. coli S.O111:B4) at a dose of 50 micrograms/kg suppressed the migrating myoelectric complexes, which were replaced by continuous rhythmic clusters of rapidly propagated spike bursts for 114.7 +/- 19.9 minutes. Intraperitoneal platelet-activating factor (25 micrograms/kg) also inhibited the migrating myoelectric complex pattern for 146.1 +/- 24.1 minutes. Previous IV administration of BN 52021 (50 mg/kg-1) abolished the motor alterations induced by platelet-activating factor and significantly reduced to 43.1 +/- 12.2 minutes those induced by endotoxin (P less than 0.01). Indomethacin (10 mg/kg IP), injected before endotoxin or platelet-activating factor, also significantly reduced the duration of migrating myoelectric complex inhibition to 45.6 +/- 7.8 and 47.7 +/- 8.3 minutes, respectively (P less than 0.01). SC 19220 significantly reduced the effects of platelet-activating factor from 151.8 +/- 26.4 to 67.4 +/- 14.7 min (P less than 0.01). Superoxide dismutase (15,000 U/kg IV) injected before either endotoxin or platelet-activating factor shortened the migrating myoelectric complex inhibition to 45.7 +/- 9.9 and 72.9 +/- 10.4 minutes, respectively (P less than 0.01). Allopurinol and dimethylsulfoxide administered orally at 50 mg/kg 1 hour before endotoxin reduced the migrating myoelectric complex inhibition to 42.5 +/- 6.5 and 38.2 +/- 6.4 minutes, respectively (P less than 0.01). They also reduced platelet-activating factor-induced intestinal myoelectric alterations to 68.5 +/- 10.6 and 31.7 +/- 6.1 minutes, respectively (P less than 0.01). It is concluded that endogenous release of platelet-activating factor is partly responsible for the intestinal motor alterations induced by endotoxin, these effects being also mediated through the release of prostaglandins and free radicals. However, prostaglandins, as well as free radicals, appear to be partly involved in the platelet-activating factor-induced action of E. coli endotoxin on intestinal motility.
在长期于十二指肠空肠植入镍铬合金电极的清醒禁食大鼠中，研究了静脉注射大肠杆菌内毒素对肠道肌电活动的影响。将这些影响与血小板活化因子的影响进行比较，并在预先用特异性血小板活化因子拮抗剂BN 52021、吲哚美辛（一种选择性前列腺素E2拮抗剂，SC 19220）和几种自由基清除剂处理的动物中进行评估。以50微克/千克的剂量静脉注射内毒素（大肠杆菌S.O111:B4）可抑制移行性肌电复合波，取而代之的是持续有节律的快速传播的棘波簇，持续114.7±19.9分钟。腹腔注射血小板活化因子（25微克/千克）也可抑制移行性肌电复合波模式146.1±24.1分钟。先前静脉注射BN 52021（50毫克/千克-1）可消除血小板活化因子诱导的运动改变，并将内毒素诱导的运动改变显著缩短至43.1±12.2分钟（P<0.01）。在内毒素或血小板活化因子之前注射吲哚美辛（10毫克/千克腹腔注射），也分别将移行性肌电复合波抑制的持续时间显著缩短至45.6±7.8分钟和47.7±8.3分钟（P<0.01）。SC 19220显著降低了血小板活化因子的作用，从151.8±26.4分钟降至67.4±14.7分钟（P<0.01）。在内毒素或血小板活化因子之前静脉注射超氧化物歧化酶（15,000单位/千克），分别将移行性肌电复合波抑制缩短至45.7±9.9分钟和72.9±10.4分钟（P<0.01）。在内毒素前1小时口服给予50毫克/千克的别嘌呤醇和二甲基亚砜，分别将移行性肌电复合波抑制降至42.5±6.5分钟和38.2±6.4分钟（P<0.01）。它们还分别将血小板活化因子诱导的肠道肌电改变降至68.5±10.6分钟和31.7±6.1分钟（P<0.01）。结论是，血小板活化因子的内源性释放部分导致了内毒素诱导的肠道运动改变，这些作用也通过前列腺素和自由基的释放介导。然而，前列腺素以及自由基似乎部分参与了血小板活化因子诱导的大肠杆菌内毒素对肠道运动的作用。
