联合抗介质治疗大鼠严重破坏性急性坏死性胰腺炎

Q3 Pharmacology, Toxicology and Pharmaceutics
T. Firsova, S. A. Alekhin, D. P. Nazarenko, L. Danilenko, Antonina G. Chub, E. Malyutina, T. Lazareva, L. V. Druzhikin
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引用次数: 0

摘要

简介:炎症介质在急性胰腺炎发病中起重要作用,其中肿瘤坏死因子(TNF)是最重要的炎症介质。开发有效的联合疗法可以帮助减少组织损伤,改善结果,并最终降低这种严重病理的死亡率。材料与方法:实验选用雌性Wistar大鼠120只,体重250±25g。急性胰腺炎由胆盐化合物静脉注射引起。结果与讨论:在研究过程中所获得的关于英夫利昔单抗明显的胰腺保护作用的数据可以通过其在全身炎症反应发生中的关键作用来解释,因此,在早期阻断肿瘤坏死因子α的情况下,胰腺没有明显的继发性损伤,这体现在水肿从模型中的4.87±0.03显著降低到2.75±0.04,因此,腺泡组织血供从182.38±15.92 PU提高到287.92±14.64 PU,表现为坏死区域的减少和死亡率的降低,最后,效率系数从13480.000提高到4283.348。选择性半胱氨酸白三烯阻滞剂对胰腺细胞损伤的保护作用不那么明显,但比奥曲肽的保护作用要大得多。孟鲁司特组的效率系数为8621.18,奥曲肽组的效率系数为12767.30。另一方面,英夫利昔单抗的使用效果并没有超过孟鲁司特,两者联合使用具有明显的加性效应,效率系数在2390.33水平证明了这一点。这一反应可以解释为TNF α介导的白三烯生物合成激活途径是主要的,但不是唯一的。结论:联合抗介质治疗为提高急性胰腺炎的标准治疗提供了良好的契机。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combined anti-mediator therapy for severe destructive forms of acute necrotizing pancreatitis in rats
Introduction: Inflammatory mediators play a major role in pathogenesis of acute pancreatitis with TNF (tumor necrosis factor) as the most important one. Development of effective combined therapy could help to decrease tissue damage, improve results and, finally, diminish the mortality rate in this severe pathology. Materials and methods: All the studies were performed on 120 female white Wistar rats, weighing 250±25g. Acute pancreatitis reproduced by an intracanalicular injection of bile salts compound. Results and discussion: The data obtained in the course of the study on the pronounced pancreatoprotective effect of infliximab are explained by its key role in the onset of the systemic inflammatory response, and, therefore, with the blockade of tumor necrosis factor alpha in the early stages, there is no pronounced secondary damage to the pancreas, which is reflected in a significant decrease in edema from 4.87±0.03 in the model up to 2.75±0.04, and as a consequence, an improvement in the blood supply of the acinar tissue from 182.38±15.92 PU up to 287.92±14.64 PU, which is expressed in a decrease in the zones of necrosis and in a decrease in mortality and, finally, efficiency coefficient from 13480.000 to 4283.348. A selective blocker of cysteinyl leukotrienes has a less pronounced protective reaction against damage to pancreatocytes, but to a much greater extent than octreotide. That is expressed by changes in the efficiency coefficient to the level of 8621.18 in montelukast group and 12767.30 in octreotide group, respectively. On the other hand, the effect of the use of infliximab does not surpass that of montelukast, and their combined use has a pronounced additive effect, which is proved by the efficiency coefficient at the level of 2390.33. This reaction is explained by the fact that TNF alpha-mediated pathway of activation of leukotriene biosynthesis is the main, but not the only one. Conclusion: The combined anti-mediator therapy provides a great opportunity to improve the standard therapy of acute pancreatitis.
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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