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巴西矛头蝮蛇和杜氏侏膨蝰蛇的毒液在前列腺素E2和D2的产生以及环氧化酶的表达方面引发不同的反应。

Bothrops jararaca and Crotalus durissus terrificus venoms elicit distinct responses regarding to production of prostaglandins E2 and D2, and expression of cyclooxygenases.

作者信息

Moreira Vanessa, Zamuner Stella Regina, Wallace John L, Teixeira Catarina de Fátima Pereira

机构信息

Laboratory of Pharmacology, Butantan Institute, Ave Vital Brazil, 1500, 05503-900 Sao Paulo, Brazil.

出版信息

Toxicon. 2007 Apr;49(5):615-24. doi: 10.1016/j.toxicon.2006.09.006. Epub 2006 Sep 16.

Abstract

Prostaglandins (PGs), synthesized by cyclooxygenases, play important roles in many pathophysiological processes including inflammation and hyperalgesia. In this study the profiles of PGE(2) and PGD(2) production secondary to injection of Bothrops jararaca venom (BjV), with inflammatory activity or Crotalus durissus terrificus venom (CdtV), with anti-inflammatory and antinociceptive properties, into mice were evaluated, and the ability of these venoms to induce expression of cyclooxygenases-1 (COX-1) and -2 (COX-2) was investigated. Intraperitoneal injection of BjV but not of CdtV induced the release and PGD(2) at 30 min and of PGE(2) from 3 up to 12 h after injection. Moreover, BjV up-regulated expression of COX-2 but not of the constitutive COX-1, suggesting that expressed COX-2 provides more substrate for synthesis of PGs by the respective terminal synthases, being the critical enzyme for PGs production in the late periods of BjV effect. In contrast, CdtV does not have any effect on constitutive COX-1 and do not induce expression of COX-2. Therefore, differences between BjV and CdtV in the ability to regulate PGs synthesis can account for their distinct effects with regard to inflammation. Moreover, inhibition of COX-2 by selective drugs may be of value to counteract the severe local inflammation induced by BjV in the victims.

摘要

前列腺素(PGs)由环氧化酶合成,在包括炎症和痛觉过敏在内的许多病理生理过程中发挥重要作用。在本研究中,评估了向小鼠注射具有炎症活性的巴西矛头蝮蛇毒(BjV)或具有抗炎和镇痛特性的三色矛头蝮蛇毒(CdtV)后,PGE(2)和PGD(2)的产生情况,并研究了这些蛇毒诱导环氧化酶-1(COX-1)和-2(COX-2)表达的能力。腹腔注射BjV而非CdtV可在注射后30分钟诱导PGD(2)释放,并在注射后3至12小时诱导PGE(2)释放。此外,BjV上调了COX-2的表达,但未上调组成型COX-1的表达,这表明所表达的COX-2为各自的末端合酶合成PGs提供了更多底物,是BjV作用后期PGs产生的关键酶。相比之下,CdtV对组成型COX-1没有任何影响,也不诱导COX-2的表达。因此,BjV和CdtV在调节PGs合成能力上的差异可以解释它们在炎症方面的不同作用。此外,选择性药物抑制COX-2可能有助于对抗BjV在受害者体内引起的严重局部炎症。

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