Cicardi M, Testoni P, Bergamaschini L, Guzzoni S, Cugno M, Buizza M, Bagnolo F
Istituto di Medicina Interna, Università degli Studi, Ospedale Maggiore di Milano.
Ann Ital Med Int. 1994 Jul-Sep;9(3):180-2.
Kallikrein is a protease involved in the inflammatory process causing acute pancreatitis. Attempts to prevent this process with antiprotease agents have been successful in experimental animal models but disappointing in humans. We studied 40 consecutive patients undergoing endoscopic papillosphincterotomy. This procedure can induce a transient, moderate pancreatic inflammatory reaction, characterized by hyperamylasemia, which in 1-6% of the patients may evolve to acute pancreatitis. To assess the capacity of C1 inhibitor, the main physiological inhibitor of kallikrein, to prevent such complications, we pretreated 20 patients with 3000 U of C1 inhibitor plasma concentrate i.v.; 20 patients served as controls. Serum levels of amylase and functional C1 inhibitor were determined before the procedure and after 2, 4, 8 and 24 hours. Serum levels of amylase in the control group (146 +/- 21 IU) and in the group treated with C1 inhibitor (158 +/- 25 IU) were similar before treatment. Four and 8 hours after the end of the procedure, amylase levels were significantly lower (p < 0.001) in the treated group (231 +/- 46 and 355 +/- 104 IU) than in the control subjects (969 +/- 229 and 923 +/- 207 IU). After 24 hours both groups had normal amylase levels. In treated patients, functional levels of C1 inhibitor increased from 104 +/- 30 to 175 +/- 30% and remained elevated throughout the observation period. These data indicate that C1 inhibitor plasma concentrate can prevent hyperamylasemia following pancreas injury, probably, by inhibiting the kallikrein-mediated inflammatory process. C1 inhibitor might benefit patients at high risk of pancreatitis who undergo endoscopic papillosphincterotomy.
激肽释放酶是一种参与导致急性胰腺炎的炎症过程的蛋白酶。在实验动物模型中，使用抗蛋白酶药物预防这一过程已取得成功，但在人类身上却令人失望。我们研究了40例连续接受内镜乳头括约肌切开术的患者。该手术可诱发短暂的、中度的胰腺炎症反应，其特征为高淀粉酶血症，在1% - 6%的患者中可能会发展为急性胰腺炎。为了评估激肽释放酶的主要生理抑制剂C1抑制剂预防此类并发症的能力，我们对20例患者静脉注射3000 U的C1抑制剂血浆浓缩物进行预处理；20例患者作为对照。在手术前以及术后2、4、8和24小时测定淀粉酶和功能性C1抑制剂的血清水平。治疗前，对照组（146 ± 21 IU）和接受C1抑制剂治疗组（158 ± 25 IU）的淀粉酶血清水平相似。手术结束后4小时和8小时，治疗组（231 ± 46和355 ± 104 IU）的淀粉酶水平显著低于对照组（969 ± 229和923 ± 207 IU）（p < 0.001）。24小时后，两组的淀粉酶水平均恢复正常。在接受治疗的患者中，功能性C1抑制剂水平从104 ± 30%升高至175 ± 30%，并在整个观察期内保持升高。这些数据表明，C1抑制剂血浆浓缩物可能通过抑制激肽释放酶介导的炎症过程来预防胰腺损伤后的高淀粉酶血症。C1抑制剂可能会使接受内镜乳头括约肌切开术的胰腺炎高危患者受益。
