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英夫利昔单抗抗 TNF-α 治疗对重症急性坏死性胰腺炎胰腺组织损伤的作用。

Effect of Anti-TNFα Therapy by Infliximab against Pancreatic Tissue Damage in Severe Acute Necrotizing Pancreatitis.

机构信息

Belgorod State University, Pobedy St., 85, Belgorod, 308015, Russia.

出版信息

Arch Razi Inst. 2021 Nov 30;76(5):1237-1244. doi: 10.22092/ari.2021.355845.1726. eCollection 2021 Nov.

Abstract

Nowadays, it is difficult to find a more complicated inflammatory disease of the abdominal organs in its pathogenesis than acute pancreatitis (AP). The application of antimediatory drugs and antimetabolites is the most promising direction in the correction of inflammatory pathological processes. The study of possible applications of a new group of drugs (monoclonal antibodies) that may trigger inflammation is also of great interest. The present study aimed to study the effect of infliximab on the lethality, volume, and nature of pancreatic lesions in severe necrotizing ductal pancreatic necrosis. The study was conducted on female Wistar rats (n=30) of similar age in the weight range of 200-250g. All manipulations were performed under general anesthesia by intraperitoneal injection of zoletil at a dose of 60 mg/kg, as well as chloral hydrate at a dose of 125 mg/kg. Model of severe acute necrotizing pancreatitis was performed through the injection of 0.5 ml of a buffer solution containing a bile acid salt-sodium taurocholate introductory. The animals were divided into the following groups: Group A (n=6): normal values; Group B (n=6): the mortality study was conducted in acute destructive pancreatitis in a period of 24 h; Group C (n=6): the simulation of acute severe necrotic pancreatitis was performed in this group along with the study of the volume of pancreatic lesions for a period of 6 h from the moment of modeling; Group D (n=6): in this group, the effect of infliximab (at a dose of 60 mkg/kg) was studied on mortality in severe destructive pancreatitis for a period of 24 h from the moment of modeling; Group E (n=6): in this group, the effect of infliximab (at a dose of 120 mkg/kg) was studied on the volume of pancreatic lesions in severe destructive pancreatitis for a period of 6 h from the moment of modeling. During the assessment of pancreatic damage, the mean±SD volume of pancreatic lesions was determined to be 34.8%±1.2% in a period of 6 h after modeling. Assessment of pancreatic damage in group E and the protective effect of infliximab at a dose of 60 mg/kg showed that the total volume of the necrotic pancreatic lesion was determined to be 21.3%±1.4% after a period of 6 h from the moment of AP modeling. In the course of this study, it was revealed that the application of infliximab at a dose of 60 mcg/kg led to a pronounced positive effect on the pancreatic lesion, manifested by up to 50% decrease in mortality for one day in group D. Infliximab had a definite protective effect in AP, decreasing the volume of the injury, as well as the mortality rate by half for 24 h. Therapy with anti-tumor necrosis factor with infliximab could significantly reduce the volume of pancreatic lesions in severe forms of pancreatic necrosis, which contributed to a pronounced decrease in mortality for 1 day from the moment of pathology reproduction.

摘要

如今,在发病机制方面,很难找到比急性胰腺炎(AP)更复杂的腹部器官炎症性疾病。抗炎药物和代谢物的应用是纠正炎症病理过程的最有前途的方向。研究新的一组药物(单克隆抗体)可能引发炎症的可能应用也非常有意义。本研究旨在研究英夫利昔单抗对严重坏死性导管性胰腺炎的致死率、胰腺病变体积和性质的影响。该研究在年龄相似、体重在 200-250g 范围内的雌性 Wistar 大鼠(n=30)上进行。所有操作均在全身麻醉下通过腹腔内注射佐替利(剂量为 60mg/kg)和水合氯醛(剂量为 125mg/kg)进行。通过注射含有胆汁酸盐-牛磺胆酸钠的缓冲溶液来建立严重急性坏死性胰腺炎模型。动物被分为以下几组:A 组(n=6):正常值;B 组(n=6):在 24 小时的急性破坏性胰腺炎中进行死亡率研究;C 组(n=6):在该组中,在建模后 6 小时内对急性严重坏死性胰腺炎进行模拟,并研究胰腺病变的体积;D 组(n=6):在该组中,在建模后 24 小时内,研究英夫利昔单抗(剂量为 60mkg/kg)对严重破坏性胰腺炎的致死率的影响;E 组(n=6):在该组中,研究英夫利昔单抗(剂量为 120mkg/kg)对建模后 6 小时内严重破坏性胰腺炎胰腺病变体积的影响。在评估胰腺损伤时,建模后 6 小时胰腺病变的平均±SD 体积为 34.8%±1.2%。在 E 组中评估胰腺损伤和英夫利昔单抗(剂量为 60mg/kg)的保护作用表明,在 AP 建模后 6 小时,坏死性胰腺病变的总体积确定为 21.3%±1.4%。在本研究过程中,发现英夫利昔单抗(剂量为 60μg/kg)的应用对胰腺病变具有显著的积极作用,在 D 组中,在一天内死亡率降低了 50%。英夫利昔单抗对 AP 具有明确的保护作用,将损伤体积降低一半,24 小时内死亡率降低一半。用英夫利昔单抗进行抗肿瘤坏死因子治疗可显著减少严重胰腺坏死形式的胰腺病变体积,从而使从发病到第 1 天的死亡率显著降低。

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