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血小板活化因子拮抗剂对猪急性重症胰腺炎后肺和气管粘膜损伤的影响

d in grinding tubes. The homogenate was centrifuged and the supernatants were collected for the assays of NE, PLA2, MPO and PAF. Results The activities of NE, PLA2 and MPO and the levels of PAF in lung and tracheal mucosa increased significantly in ASP pigs. There are significantly positive relationships between PAF and NE, PLA2, MPO or W/D in lung and tracheal mucosa. The PAF levels in lung and tracheal mucosa and the severity of acute lung injury induced by PMN sequestration, NE and activated PLA2 reduced remarkably by the pre-and post-treatment with BN50739. Conclusions PAF plays an important role in acute lung injury in porcine ASP, which may be associated with the increments of PMN sequestration, NE and the highly activated PLA2 in lung and tracheal mucosa. The pre-and post-treatment with BN50739 can effectively reduce the PAF levels in lung and tracheal mucosa and the severity of acute lung injury following ASP via reducing the PMN sequestration and the amount of elastase, and by inhibiting PLA2 activities in lung and tracheal mucosa.

  【Key words】 Acute severe pancreatits; Platelet-activating factor; BN50739; Acute lung injury; Elastase

  血小板活化因子(PAF)在诸多炎症反应如急性重症胰腺炎(ASP)的病理损伤过程中起着重要作用[1-3],而预防性应用PAF受体拮抗剂如WEB21270、BN5021可以明显减轻胰腺炎性肺损伤[2]。但有关PAF拮抗剂对ASP后肺损伤的保护机制仍不很清楚。BN50739是一种新型PAF特异性受体拮抗剂。有研究显示,BN50739对缺血再灌注后脑损伤[4]、心肌损伤和心律失常[5-8],内毒素介导性肝损伤[9,10]、红细胞膜损伤[11],嗜中性粒细胞(PMN)介导性心肌损伤有明显的保护作用[12,13]。但尚未见有关BN50739对猪ASP后PMN、嗜中性粒细胞弹性蛋白酶(NE)、磷脂酶A2(PLA2)介导性肺损伤保护作用研究的报道。

  材料与方法

  一、动物分组

  选健康长白种猪28只(南京军区动物实验中心提供),体重16~22 kg,雌雄不限,随机分为5组:Ⅰ组(假手术对照组,5只);Ⅱ组(ASP对照组,6只);Ⅲ组[二甲亚砜(DMSO)对照组5只];Ⅳ组(ASP+PAF受体拮抗剂预防组,6只);Ⅴ组(ASP+PAF受体拮抗剂治疗组,6只)。在麻醉状态下,进腹向胰总管内注入1 ml/kg 5%牛磺胆酸钠混合液(内含40~50 IU/ml胰蛋白酶,pH7.6)诱导ASP。以0.9% NaCl磷酸盐缓冲液取代5%牛磺酸钠混合液即为假手术对照组。

  二、BN50739配制和使用

  PAF特异性受体拮抗剂BN50739由法国Braquet P博士惠赠。Ⅳ组即ASP+PAF受体拮抗剂预防组,按10 mg/kg BN50739于ASP诱导前30 min溶于64%~66% DMSO,配成3.2%~3.3%浓度,缓慢从腔静脉内注

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