血小板活化因子在烧伤合并内毒素血症早期肺损伤中的作用及意义

目的　探讨血小板活化因子（ＰＡＦ） ,肿瘤坏死因子（ＴＮＦ）等在烧伤合并内毒素血症早期肺损伤中的作用及意义。方法　采用２０ ％ ＴＢＳＡⅢ度烧伤合并内毒素注射复制大鼠早期肺损伤模型,检测血浆ＰＡＦ、ＴＮＦ含量等,观察肺组织病理形态学变化并应用ＰＡＦ受体拮抗剂防治早期肺损伤。结果　ＰＡＦ是烧伤合并内毒素血症早期先于ＴＮＦ出现变化的炎症介质,血浆ＰＡＦ浓度与早期肺损伤程度呈正相关,注射ＰＡＦ受体拮抗剂ＢＮ５０７３９ 可使肺损伤程度减轻。结论　ＰＡＦ在烧伤合并内毒素血症早期肺损伤中起重要致病作用     

血小板活化因子在烧伤合并内毒素血症早期肺损伤中的作用及意义

目的探讨血小扳活化因子(PAF),肿瘤坏死因子(TNF)等在烧伤合并内毒素血症早期肺损伤中的作用及意义。方法采用20%TBSAⅢ度烧伤合并内毒素注射复制大鼠早期肺损伤模型,检测血浆 PAF、TNF 含量等,观察肺组织病理形态学变化并应用 PAF 受体拈抗剂防治早期肺损伤。结果 PAF 是烧伤合并内毒素血症早期先于 TNF 出现变化的炎症介质,血浆 PAF 浓度与早期肺损伤程度呈正相关,注射 PAF 受体拮抗剂 BN50739可使肺损伤程度减轻。结论 PAF 在烧伤合并内毒素血症早期肺损伤中起重要致病作用。     

烧伤并发内毒素血症早期肝损害与TNF-α mRNA表达的实验研究

目的观察ＴＮＦαｍＲＮＡ及其蛋白的组织分布和细胞定位,探讨烧伤并发内毒素血症早期肝损害的发生机理。方法选用２０％Ⅲ度ＴＢＳＡ烧伤大鼠合并腹腔内毒素（ＬＰＳ）注射造成烧伤复合内毒素血症肝损害模型,采用光镜,电镜及免疫组化原位杂交染色观察大鼠肝脏的形态功能变化、血清ＴＮＦα含量变化、肝组织ＴＮＦα和ＴＮＦαｍＲＮＡ的细胞定位及其分布。结果烧伤复合内毒素血症组,光镜下主要表现肝窦反应,枯否细胞（ＫＣｓ）激活与增生以及肝细胞（ＨＣｓ）变性坏死等;电镜下主要表现肝窦内血小板聚集、纤维素沉积与中性粒细胞（ＰＭＮｓ）扣押以及ＫＣｓ、肝细胞退变溶解等。血清丙氨酸氨基转氨酶（ＡＬＴ）显著升高（Ｐ＜０．０１）和白蛋白（ＡＬＢ）轻度下降。组织ＴＮＦα主要定位于肝窦内皮细胞（ＳＥＣｓ）、ＫＣｓ。ＴＮＦαｍＲＮＡ主要定位于ＫＣｓ、ＰＭＮｓ、巨噬细胞（ＭＰｓ）。而在单因素组主要特点为病变程度轻,肝功能损害不明显,血清ＴＮＦα峰值滞后以及组织ＴＮＦα和ＴＮＦαｍＲＮＡ表达相对较弱等。结论ＴＮＦα是参与烧伤复合内毒素血症早期肝脏损害的重要细胞因子。     

杀菌/通透性增加蛋白对休克大鼠肺组织细胞因子mRNA表达的影响

作者在大鼠失血性休克（４ｋＰａ，１８０分钟）模型上，观察了重组杀菌／通透性增加蛋白（ＢＰＩ）对肺组织肿瘤坏死因子（ＴＮＦ）、白介素－６（ＩＬ－６）ｍＲＮＡ表达及急性肺损伤的影响，并对肠源性内毒素血症与炎症细胞因子诱发的关系进行了探讨。结果显示：失血性休克可导致血浆内毒素含量显著升高，肺组织ＴＮＦ、ＩＬ－６ｍＲＮＡ表达分别在复苏后２、８小时明显增多（Ｐ＜０．０５～０．０１）；给予ＢＰＩ治疗则完全中和休克所致内毒素血症，并不同程度地抑制肺组织ＴＮＦ、ＩＬ－６ｍＲＮＡ的表达（Ｐ＜０．０５～０．０１）；肺毛细血管通透性与髓过氧化物酶活性均明显降低。作者认为，ＢＰＩ可有效防止失血性休克诱发的急性肺损伤，其作用机制可能与抑制肠源性内毒素血症所介导的局部组织炎症细胞因子基因表达有关。     

己酮可可碱对内毒素肺损伤肺组织TNFmRNA表达的影响

目的：观察己酮可可碱对内毒素血症引起的肺组织ＴＮＦｍＲＮＡ表达及血浆ＴＮＦ的影响。方法：选用ＳＤ大鼠６３只，分三组：①生理盐水组（Ｃ组）；②内毒素组（Ｅ组），大肠杆菌Ｏ５５Ｂ５内毒素１５ｍｇ／ｋｇ静注；③内毒素＋己酮可可碱组（Ｅ＋Ｐ组），１５ｍｇ／ｋｇ内毒素加２０ｍｇ／ｋｇ己酮可可碱静注，６ｍｇ／ｋｇ己酮可可碱维持。每组分１、３、６小时三个时间点，用差别聚合酶链反应测定肺组织ＴＮＦｍＲＮＡ的变化，双抗体夹心法测定血浆ＴＮＦ的变化。结果：内毒素组血浆ＴＮＦ在１小时达高峰，３小时仍升高，６小时接近生理盐水组水平，己酮可可碱组１小时和３小时血浆ＴＮＦ与相应内毒素组比明显下降（Ｐ分别＜０．０１，０．０５）；ＴＮＦｍＲＮＡ表达在内毒素组１小时和３小时明显升高，己酮可可碱治疗后ＴＮＦｍＲＮＡ表达和内毒素组比明显下降（Ｐ＜０．０１），己酮可可碱组病理损害明显减轻。结论：ＴＮＦ是一个早期的重要炎症介质，己酮可可碱能抑制ＴＮＦ的产生，通过抑制其转录而产生作用，己酮可可碱对内毒素肺损伤具有保护作用。     

杀菌／通透性增加蛋白对休克大鼠组织细胞因子mRNA表达的影响

作者在大鼠失血性休克模型上,观察了重组杀菌／通透性增加蛋白（ＢＰＩ）对肺组织肿瘤坏死因子（ＴＮＦ）、白人素－６（ＩＬ－６）ｍＲＮＡ表达及急性肺损伤的影响,并对肠源性内毒素血症与炎症细胞因子诱发的关系进行了探讨。结果显示：失血性休克可导致血浆内毒素含量显著升高,肺组织ＴＮＦ,ＩＬ－６ｍＲＮＡ表达分别在复苏后２、８小时明显增多（Ｐ〈０．０５－０．０１）;给予ＢＰＩ治疗则完全中和休克所致内毒素血症,并不     

利多卡因对兔内毒素性肺损伤后早期的治疗作用

目的：探讨利多卡因对兔内毒素性肺损伤后早期的治疗效应。方法：２４只大耳白兔随机分为对照组、内毒素（ＥＴ）致病组、ＥＴ致病加利多卡因治疗组。分别用酶联免疫法和硫代巴比妥酸反应法测量血浆和支气管肺泡灌洗液（ＢＡＬＦ）肿瘤坏死因子（ＴＮＦα）和丙二醛（ＭＤＡ）含量。结果：利多卡因治疗组于静注ＥＴ后３、５小时血浆和ＢＡＬＦ中ＴＮＦα和ＭＤＡ含量、肺湿干重比值、ＢＡＬＦ中性粒细胞数、白蛋白、Ｃ３ａ、Ｃ５ａ均显著低于ＥＴ致病组。提示利多卡因抑制肺内补体激活和中性粒细胞在肺内聚集，减轻脂质过氧化反应和炎症介质释放。结论：利多卡因对内毒素性肺损伤后早期有治疗作用。     

热毒清对家兔内毒素性DIC急性肺损伤的保护作用

采用间隔２４小时两次注射大肠杆菌内毒素方法复制家兔急性肺损伤模型，检测血浆、肺组织及支气管肺泡灌洗液（ＢＡＬＦ）中白细胞介素８（ＩＬ－８）、硝酸盐／亚硝酸盐（ＮＯ２／ＮＯ３）水平及有关指标改变，观察中药制剂热毒清（ＲＤＱ）对家兔内毒素性肺损伤的保护作用。发现ＲＤＱ可降低肺系数及通透指数，减少ＢＡＬＦ中白细胞计数；ＩＬ－８、ＮＯ２－／ＮＯ３－水平、酸性磷酸酶（ＡＣＰ）活性亦显著降低（Ｐ＜０．０１），肺组织学损伤减轻。证实ＲＤＱ对内毒素所致的家兔急性肺损伤具有一定的保护作用。     

肿瘤坏死因子mRNA在严重烫伤大鼠小肠中的表达及细胞定位的研究

为探讨严重烫伤后肿瘤坏死因子（ＴＮＦ）在大鼠小肠中的表达及细胞定位，应用斑点杂交及原位杂交方法，结合血浆ＴＮＦ、内毒素浓度的变化，探讨了ＴＮＦｍＲＮＡ的表达及细胞定位规律。结果发现，烧伤后小肠ＴＮＦｍＲＮＡ的表达量迅速升高，在伤后６小时达峰值，是正常值的５．５６倍。门静脉血浆ＴＮＦ、内毒素的变化与之类似。正常大鼠小肠有少量的细胞表达ＴＮＦｍＲＮＡ，主要是小肠固有层内的单核吞噬细胞。烧伤后固有层内的阳性细胞明显增多，而且固有层毛细管内皮细胞表达也是阳性，隐窝内也出现大量的阳性细胞。提示：ＴＮＦ的表达分泌，在烧伤早期与肠源性内毒素血症有非常密切的联系。固有层及粘膜下层间质中的内皮细胞及单核吞噬细胞是肠道分泌ＴＮＦ的主要细胞。ＴＮＦ分泌量明显增加，其结果是造成小肠局部微循环障碍或诱导自由基的产生，从而导致肠粘膜屏障的破坏。     

烧伤休克微循环障碍及其与TNF的关系

为了探讨大鼠烧伤休克早期血浆ＴＮＦ含量和微循环的变化，以及虎杖４号对上述变化的影响，我们采用复制的大鼠ＴＢＳＡ３５％～４０％烧伤休克模型。用Ｌ９２９细胞株生物法测定了血浆ＴＮＦ含量的变化。在显微电视放大４０００倍条件下观察大鼠脊斜肌微循环变化，对部分动物的肺做了病理形态学观察，并观察了虎杖４号对上述改变的影响。结果表明，大鼠烧伤休克早期血浆肿瘤坏死因子（ＴＮＦ）含量即明显升高，其升高程度与微循环中ＷＢＣ附壁粘着及毛细血管的关闭程度呈明显的正相关。应用虎杖４号可明显抑制烫伤后血浆ＴＮＦ的升高，同时亦明显减轻ＷＢＣ的附壁粘着和肺损伤。提示烫伤后血浆ＴＮＦ的升高参与了ＷＢＣ的粘着和微循环紊乱的发生。     

Platelet activating factor receptor antagonist improves survival and attenuates eicosanoid release in severe endotoxemia.

Exogenous platelet activating factor (PAF) causes hypotension, plasma extravasation, metabolic acidosis, and death. These effects are similar to those of endotoxin as well as the eicosanoids. A specific PAF receptor antagonist, BN52021, was used to determine its effects on the hemodynamic events, the eicosanoid production, and on survival in severe rat endotoxemia. Endotoxin alone significantly produced hypotension, prostaglandins (TxB2, PGE2) release, and death. In contrast pretreatment with BN52021, a specific PAF receptor antagonist, significantly altered the hypotension, significantly attenuated the eicosanoid release, and improved the survival rate (p less than 0.01). These findings suggest that PAF receptor activation is an early event in endotoxemia. Eicosanoid release in endotoxemia could be related to PAF synthesis and PAF receptor activation. These findings support the hypothesis that there may be an intimate relationship between PAF and the eicosanoids and that in endotoxemia some of the effects of PAF may be mediated via the cyclo-oxygenase pathway.     

Role of platelet-activating factor in leukocyte-independent plasma extravasation and mast cell activation during endotoxemia

BACKGROUND: Independently from leukocyte adherence, endothelial factors and mast cell activation seems to promote microvascular permeability. Platelet-activating factor (PAF) has been shown to play a significant role in endotoxin-induced leukocyte adherence. The aim of our study was to investigate if there is also a role for PAF in mediating leukocyte-independent microvascular permeability changes and activation of mast cells during endotoxemia. Therefore, during endotoxemia microvascular permeability and mast cell activation were determined after inhibition of L-selectin-mediated leukocyte adherence by fucoidin and after inhibition of PAF effects by the PAF receptor antagonist BN52021. MATERIALS AND METHODS: In male Wistar rats, red cell velocity (V(RBC)), venular wall shear rate, microvascular permeability, leukocyte adherence, and mast cell activation were determined in mesenteric postcapillary venules using intravital microscopy at baseline and 60 and 120 min after start of a continuous infusion of endotoxin (ETX; 2 mg/kg/h, Escherichia coli O26:B6) (ETX group). Animals in the FUCO/ETX group received fucoidin (25 mg/kg body wt) in addition to the procedure described above. Animals in the FUCO/ETX/PAF-ANT group received fucoidin and the PAF receptor antagonist BN52021 (5 mg/kg body wt) prior to the continuous endotoxin infusion. Control animals (control group) received only equivalent volumes of NaCl 0.9%. RESULTS: There were no microhemodynamic and macrohemodynamic differences between groups. In all endotoxin-challenged groups macromolecular leakage and mast cell activity increased significantly, starting at 60 min. Both macromolecular leakage and mast cell activity were significantly higher in the FUCO/ETX group than in the FUCO/ETX/PAF-ANT group and control group. Differences in macromolecular leakage between groups were significant at 120 min. Differences in mast cell activity between groups were significant at 60 and 120 min. CONCLUSIONS: The results of our study demonstrate a leukocyte-independent plasma extravasation that can be inhibited by the PAF receptor antagonist BN52021, indicating the involvement of PAF in the pathophysiology of leukocyte-independent microvascular damage during early endotoxemia. Mast cell activity seems to precede leukocyte-independent macromolecular leakage.     

急性坏死性胰腺炎大鼠血浆内皮素的改变及其意义

为了解急性坏死性胰腺炎（ａｃｕｔｅ ｎｅｃｒｏｔｉｚｉｎ ｐａｎｃｒｅａｔｉｔｉｓ,ＡＮＰ）时血浆内皮素（ｅｎｄｏｔｈｅｌｉｎ,ＥＴ）的变化及其病理意义,进行了前瞻性动物实验。即将ＳＤ大鼠随机分为３组：急性坏死性胰腺炎组（ＡＮＰ组,ｎ＝２）,组胆胰管注入５％牛磺胆酸钠（ＳＴＣ １ｍｌ／ｋｇ）制造ＡＮＰ模型,假手术组（ＳＯ组,ｎ＝２４）和血小板激活因子拮抗剂ＢＮ５０７３９组（ＢＮ组,ｎ＝２４）。测定     

Platelet-activating factor and progressive brain damage following focal brain injury

The effects of a platelet-activating factor (PAF) antagonist on brain edema, cortical microcirculation, blood-brain barrier (BBB) disruption, and neuronal death following focal brain injury are reported. A neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used to induce highly reproducible focal cortical lesions in anesthetized rats. Secondary brain damage in this model was characterized by progressive cortical hypoperfusion, edema, and BBB disruption in the vicinity of the hemispheroid lesion occurring acutely after injury. The histopathological evolution was followed for up to 4 days. Neuronal damage in the cortex and the hippocampus (CA-1) was assessed quantitatively, revealing secondary and progressive loss of neuronal tissue within the first 24 hours following injury. Pretreatment with the PAF antagonist BN 50739 ameliorated the severe hypoperfusion in 12 rats (increasing local cerebral blood flow from a mean +/- standard error of the mean of 40.5% +/- 8.3% to 80.2% +/- 7.8%, p less than 0.01) and reduced edema by 70% in 10 rats (p less than 0.05) acutely after injury. The PAF antagonist also reduced the progression of neuronal damage in the cortex and the CA-1 hippocampal neurons (decrease of neuronal death from 88.0% +/- 3.9% to 49.8% +/- 4.2% at 24 hours in the cortex and from 40.2 +/- 5.0% to 13.2% +/- 2.1% in the hippocampus in 30 rats; p less than 0.05). This study provides evidence to support progressive brain damage following focal brain injury, associated with secondary loss of neuronal cells. In this latter process, PAF antagonists may provide significant therapeutic protection in arresting secondary brain damage following cerebral ischemia and neurological trauma.     

Pulmonary microcirculatory changes in acute lung injury in rats induced by burns and endotoxin administration

An animal model of acute pulmonary injury similar to adult respiratory distress syndrome (ARDS) was produced by intravenous injection of E. coli endotoxin to burned rats. The changes in pulmonary microcirculation were observed in vivo with "pleura window" method and the cast of the lung capillaries was studied using scanning electron microscope. The histological changes in the lung in these rats were observed with transmission electron microscope. It was shown that lung vessels constricted, microvascular permeability increased, pulmonary edema occurred and leukocytes and aggregated platelets accumulated in lung capillaries. This study suggested that pulmonary microcirculatory changes are the pathological basis of acute lung injury induced by burns accompanied with endotoxemia.     

血小板活化因子及其受体对颈髓损伤后血脊髓屏障损害的分子机制研究

目的：探讨血小板活化因子（ＰＡＦ）及其受体对颈髓损伤后血脊髓屏障损害的分子机制。方法：采用蛛网膜下腔注射ＰＡＦ及静脉注射ＰＡＦ受体拮抗剂ＢＮ５２０２１，应用地高辛标记ｃＤＮＡ探针原位杂交技术检测颈髓损伤后颈髓血管内皮细胞细胞间粘附分子－１ｍＲＮＡ（ＩＣＡＭ－１ｍＲＮＡ）和内皮细胞白细胞粘附分子－１ｍＲＮＡ（ＥＬＡＭ－１ｍＲＮＡ）表达。观察ＰＡＦ及其受体拮抗剂对颈髓损伤后血脊髓屏障、ＩＣＡＭ－１ｍＲＮＡ、ＥＬＡＭ－１ｍＲＮＡ表达的影响。结果：伤后颈髓血管内皮细胞ＩＣＡＭ－１ｍＲＮＡ、ＥＬＡＭ－１ｍＲＮＡ表达、伊文思蓝含量、水含量呈不同程度的增加；ＰＡＦ可使伤后血管内皮细胞ＩＣＡＭ－１ｍＲＮＡ、ＥＬＡＭ－１ｍＲＮＡ表达、伊文思蓝含量、水含量增加更为显著，ＰＡＦ受体拮抗剂可抑制ＩＣＡＭ－１ｍＲＮＡ、ＥＬＡＭ－１ｍＲＮＡ表达，降低颈髓组织伊文思蓝含量及水含量。结论：ＰＡＦ通过增加伤后颈髓血管内皮细胞粘附分子的表达是导致血脊髓屏障损害的重要分子基础。ＰＡＦ受体对伤后血管内皮细胞细胞粘附分子的表达具有调控作用。     

Impact of PAF antagonist BN 52021 (Ginkolide B) on post-ischemic graft function in clinical lung transplantation.

BACKGROUND: Platelet activating factor (PAF) is associated with ischemia/reperfusion injury (I/R) after lung transplantation. Following promising experimental results, this prospective trial investigated the potential effect of PAF antagonist BN 52021 (ginkolide B) on clinical Euro-Collins (EC)-based lung preservation. METHODS: We analyzed 8 double-lung transplant patients in each of 3 groups. In the low-dose group (LDG), donor lungs were perfused with EC containing 2 mg/kg BN 52021, whereas we used 10 mg/kg in the high-dose group (HDG) and placebo in the control group (CG). Before reperfusing the first lung, we administered intravenously 120 mg BN 52021 (LDG), 600 mg BN 52021 (HDG), or placebo (CG). Hemodynamics in terms of pulmonary arterial pressure, pulmonary vascular resistance and serial determinations of the alveolo-arterial oxygen difference (AaDO(2)) were recorded. We measured blood levels of PAF pre-operatively and post-operatively, after 10 minutes and after 3, 8, 24, 48, and 144 hours. RESULTS: Within 32 hours, we noted a tendency toward better AaDO(2) in the LDG and the HDG compared with the CG (p > 0.05). We observed a significant improvement of AaDO(2) after 3 hours (HDG, p = 0.033) and 8 hours (LDG, p = 0.024), with poorest values in the CG. The PAF concentrations were lowest in the HDG, with significant deterioration 10 minutes after reperfusion. In contrast, placebo led to higher PAF levels. We measured significantly lower PAF concentrations (HDG vs CG) at 10 minutes and at 6 days post-operatively. CONCLUSIONS: Use of high-dose PAF antagonist BN 52021 can easily be combined with clinical preservation methods and may help optimize pulmonary function with reduced PAF levels, in the early post-ischemic period.     

烧伤并发内毒素血症早期肝损害与TNF—αmRNA表达的实验研究

目的 观察TNF－αmRNA及其蛋白的组织分布和细胞定位,探讨烧伤并发内毒素血症早期肝损害的发生机理。方法 选用20％Ⅲ度TBSA烧伤大鼠合并腹腔内毒素（LPS）注射造成烧伤复合内毒素血症肝损害模型,采用光镜,电镜及免疫组化原位杂交染色观察产肝脏的形态功能变化、血清TNF－α含量变化、肝组织TNF－α和TNF－α mRNA的细胞定位及其分布。结果 烧伤复合内毒素血症组,光镜下主要表现肝窦反应,枯否细胞（KCs)激活与增生以及肝细胞（HCs)变性坏死等;电镜下主要表现肝窦内血小板聚集、纤维素沉积与中性粒细胞（PMNs)扣押以及KCs、肝细胞退变溶解等。血清丙氨酸氨基转氨酶（ALT）显著升高（P＜0．01）和白蛋白（ALB）轻度下降。组织TNF－α主要定位于肝窦内皮细胞（SECs)、KCs。TNF－αmRNA主要定位于KCs、PMNs、巨噬细胞（MPs)。而在单因素组主要特点为病变程度轻,肝功能损害不明显,血清TNF－α峰值滞后以及组织TNF－α和TNF－αmRNA表达相对较弱等。结论 TNF－α是参与烧伤复合内毒素血症早期肝脏损害的重要细胞因子。     

Platelet-activating factor antagonists do not attenuate delayed posttraumatic cerebral edema in rats

Platelet-activating factor (PAF) receptor antagonists reportedly improve early postischemic neurological recovery and cerebral blood flow in selected experimental models. Their effects on posttraumatic cerebral edema have, however, not been examined. In a rat model of right hemispheric percussive cerebral trauma, we examined the effects of two PAF receptor antagonists on posttraumatic edema formation. Two groups of rats received either BN 52021 (n = 14) or WEB 2086 (n = 11), 10 mg/kg i.v. at 15 min posttrauma. Two other groups treated with the BN 52021 (n = 17) and WEB 2086 (n = 10) vehicles served as controls. Hemispheric percent brain water was determined at 24 h. Edema occurred in all groups. Neither PAF receptor antagonist significantly reduced right hemispheric percent brain water (81.08 +/- 0.25 and 81.04 +/- 0.15 in Bn 52021 and WEB 2086-treated rats, respectively, versus 81.31 +/- 0.23 and 81.14 +/- 0.17% brain water in BN 52021 vehicle and WEB 2086 vehicle-treated rats). Mortality was not statistically different between groups. These data do not support a major role for PAF in the development of posttraumatic cerebral edema.     

Beneficial effects of recombinant platelet-activating factor acetylhydrolase and BN 52021 on bacterial translocation in cerulein-induced pancreatitis

BACKGROUND: Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after acute pancreatitis (AP). The aim of this study was to investigate the effects of the platelet-activating factor (PAF) inactivator, recombinant PAF-acetylhydrolase (rPAF-AH), and the PAF receptor antagonist, BN 52021, in AP. METHODS: Forty-eight male Wistar rats were divided into 4 groups: the sham group received saline intraperitoneally every hour for 6 h; the control group received cerulein 50 g/kg i.p. every hour for 6 h; the rPAF-AH group received AP plus rPAF-AH (5 mg/kg i.v. bolus), and the BN52021 group received AP plus BN 52021 (5 mg/kg i.v. bolus). The animals were sacrificed 12 h after the first cerulein injection. RESULTS: Supramaximal cerulein stimulation induced an increase in serum pancreatic enzymes, interleukin (IL)-6, pancreatic edema, and produced histologic evidence of AP. Compared with the control group, the addition of PAF receptor antagonists had a significant effect on serum pancreatic enzymes, pancreatic edema, and the histologic score of the pancreatitis. AP caused significant increases in BT in mesenteric lymph nodes (MLNs), pancreas, liver, spleen and blood. Compared with the control group, both rPAF-AH and BN 52021 decreased BT in the pancreas and blood. In addition, rPAF-AH decreased BT in the MLNs. We also found that PAF receptor antagonists suppressed the elevation in IL-6 levels. CONCLUSION: PAF antagonists attenuated the severity of experimental AP and reduced pancreatitis-induced BT to distant sites.