Camargo Enilton A, Esquisatto Laura C M, Esquisatto Marcelo A, Ribela Maria Teresa C P, Cintra Adélia C, Giglio José R, Antunes Edson, Landucci Elen C T
Departament of Pharmacology, Faculty of Medical Sciences, State University of Campinas, UNICAMP, P.O. Box 6111, SP, Brazil.
Toxicon. 2005 Dec 15;46(8):921-6. doi: 10.1016/j.toxicon.2005.09.001. Epub 2005 Nov 2.
Acute pancreatitis (AP) is an inflammatory disease of the pancreas characterized by local inflammation and extrapancreatic effects such as lung injury. Secretory phospholipases A(2) (PLA(2)s) have been implicated in triggering AP, but their exact role to evoke AP is largely unknown. Therefore, we have tested the ability of sPLA(2)s to induce AP in rats, using venom sPLA(2)s with residual or high enzymatic activity (bothropstoxin-II and Naja mocambique mocambique venom PLA(2), respectively), as well as sPLA(2) devoid of catalytic activity (piratoxin-I). The injection of Naja m. mocambique venom PLA(2), bothropstoxin-II or piratoxin-I (300 microg/kg each) into the common bile duct increased significantly the pancreatic plasma extravasation and myeloperoxidase activity. The lung myeloperoxidase and serum amylase were also increased for all groups, although the Naja mocambique mocambique venom PLA(2) induced higher lung myeloperoxidase and serum amylase values, compared with piratoxin-I and/or bothropstoxin-II. Histopathology of pancreas and lungs in piratoxin-I-injected rats showed interstitial oedema in both tissues, and neutrophil infiltration with acinar cell necrosis in pancreas. In conclusion, sPLA(2)s induce AP in rats and the catalytic activity is not essential to induce the local effects in pancreas, although it appears to contribute partly to the remote lung injury.
急性胰腺炎（AP）是一种胰腺炎症性疾病，其特征为局部炎症和诸如肺损伤等胰腺外效应。分泌型磷脂酶A2（PLA2s）被认为与AP的触发有关，但其诱发AP的确切作用在很大程度上尚不清楚。因此，我们使用具有残留或高酶活性的蛇毒sPLA2s（分别为矛头蝮毒素-II和莫桑比克眼镜蛇毒PLA2）以及缺乏催化活性的sPLA2（pir毒素-I），测试了sPLA2s在大鼠中诱导AP的能力。向胆总管注射莫桑比克眼镜蛇毒PLA2、矛头蝮毒素-II或pir毒素-I（各300微克/千克）显著增加了胰腺血浆外渗和髓过氧化物酶活性。所有组的肺髓过氧化物酶和血清淀粉酶也均升高，不过与pir毒素-I和/或矛头蝮毒素-II相比，莫桑比克眼镜蛇毒PLA2诱导的肺髓过氧化物酶和血清淀粉酶值更高。注射pir毒素-I的大鼠胰腺和肺的组织病理学显示，两种组织均有间质水肿，胰腺有中性粒细胞浸润和腺泡细胞坏死。总之，sPLA2s可在大鼠中诱导AP，催化活性对于诱导胰腺局部效应并非必不可少，尽管它似乎部分促成了远处的肺损伤。
