阿达木单抗对大鼠实验性急性胰腺炎的改善作用。

Ameliorative effect of adalimumab on experimentally induced acute pancreatitis in rats.

机构信息

Department of Internal Medicine, Faculty of Medicine, University of Pamukkale, Denizli, Turkey.

出版信息

Pancreas. 2010 Nov;39(8):1238-42. doi: 10.1097/MPA.0b013e3181dec1a6.

DOI:10.1097/MPA.0b013e3181dec1a6

PMID:20531239

Abstract

OBJECTIVES

In this study, the effects of adalimumab (ADA), a fully humanized IgG1 monoclonal antibody to tumor necrosis factor α, on experimentally acute pancreatitis (AP) were examined.

METHODS

Healthy Wistar rats (n = 32) were randomly divided into 4 groups: group 1, AP; group 2, AP + ADA; group 3, control (physiologic saline), and group 4, physiologic saline + ADA (n = 8/group). Acute pancreatitis was induced with a retrograde injection of 3% sodium (Na)-taurocholate into the common biliopancreatic duct. Adalimumab was simultaneously administered at 50 mg/kg intraperitoneally for groups 2 and 4. Physiologic saline was administered instead of Na-taurocholate for non-AP groups. After 24 hours, serum amylase, lactate dehydrogenase, pancreatic myeloperoxidase, and malondialdehyde activities, along with pancreatic histopathology, were examined.

RESULTS

Adalimumab treatment significantly decreased serum amylase activity (AP, 2778.25 ± 298.80; AP + ADA, 2143.13 ± 221.69; control, 1541.00 ± 148.39; ADA, 1143.00 ± 256.30 U/L; P < 0.001), lactate dehydrogenase activity (AP, 2978.37 ± 364.65; AP + ADA, 2582.75 ± 164.23; control 931.25 ± 135.93; ADA, 582.62 ± 99.37 U/L; P < 0.001), myeloperoxidase activity (AP, 1.44 ± 0.20; AP + ADA, 0.86 ± 0.01; control, 0.60 ± 0.17; ADA, 0.41 ± 0.00 U/g of wet tissue; P < 0.001), malondialdehyde activity (AP, 16.94 ± 3.98; AP + ADA, 7.66 ± 2.27; control, 9.07 ± 1.00; ADA, 3.58 ± 0.30 nmol/g; P < 0.01), and total histopathologic scores (AP, 2.75 ± 0.16; AP + ADA, 1.50 ± 0.19; control, 0.00 ± 0.00; ADA, 0.00 ± 0.00; P < 0.001).

CONCLUSIONS

These results support the idea that adalimumab might be beneficial for severity of AP.

摘要

目的

本研究旨在探讨阿达木单抗（一种完全人源化的肿瘤坏死因子 α IgG1 单克隆抗体）对实验性急性胰腺炎（AP）的影响。

方法

将 32 只健康 Wistar 大鼠随机分为 4 组：AP 组、AP+ADA 组、对照组（生理盐水）和 ADA 组（生理盐水+ADA），每组 8 只。通过逆行注射 3%牛磺胆酸钠至胰胆管诱发急性胰腺炎。AP+ADA 组和 ADA 组同时给予 50mg/kg 的阿达木单抗腹腔内注射。非 AP 组给予生理盐水代替牛磺胆酸钠。24 小时后，检测血清淀粉酶、乳酸脱氢酶、胰腺髓过氧化物酶和丙二醛活性，并进行胰腺组织病理学检查。

结果

阿达木单抗治疗可显著降低血清淀粉酶活性（AP 组：2778.25±298.80；AP+ADA 组：2143.13±221.69；对照组：1541.00±148.39；ADA 组：1143.00±256.30 U/L；P<0.001）、乳酸脱氢酶活性（AP 组：2978.37±364.65；AP+ADA 组：2582.75±164.23；对照组：931.25±135.93；ADA 组：582.62±99.37 U/L；P<0.001）、髓过氧化物酶活性（AP 组：1.44±0.20；AP+ADA 组：0.86±0.01；对照组：0.60±0.17；ADA 组：0.41±0.00 U/g 湿组织；P<0.001）、丙二醛活性（AP 组：16.94±3.98；AP+ADA 组：7.66±2.27；对照组：9.07±1.00；ADA 组：3.58±0.30 nmol/g；P<0.01）和总组织病理学评分（AP 组：2.75±0.16；AP+ADA 组：1.50±0.19；对照组：0.00±0.00；ADA 组：0.00±0.00；P<0.001）。