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Mesna Alleviates Cerulein-Induced Acute Pancreatitis by Inhibiting the Inflammatory Response and Oxidative Stress in Experimental Rats
Mesna 通过抑制炎症反应和氧化应激减轻雨蛙肽诱导的大鼠急性胰腺炎
- 影响因子:2.46
- DOI:10.1007/s10620-020-06072-1
- 作者列表:"Hagar, Hanan H.","Almubrik, Sarah A.","Attia, Nada M.","Aljasser, Sarah N.
- 发表时间:2020-02-22
Abstract
Background Acute pancreatitis (AP) is a sudden inflammation of the pancreas that may be life-threatening disease with high mortality rates, particularly in the presence of systemic inflammatory response and multiple organ failure. Oxidative stress has been shown to be involved in the pathophysiology of acute pancreatitis. Aim This study is designed to investigate the possible effect of mesna on an experimental model of cerulein-induced acute pancreatitis. Methods Animals were divided into five groups: Group 1 served as a control group given the saline; group II (mesna group) received mesna at a dose of (100 mg/kg per dose, i.p.) four times; group III (acute pancreatitis group) received cerulein at a dose of (20 µg/kg/dose, s.c.) four times with 1-h intervals; group VI, cerulein + mesna, was treated with mesna at a dose of (100 mg/kg, i.p.) 15 min before each cerulein injection. Results Animals with acute pancreatitis showed elevated serum amylase and lipase levels. Biochemical parameters showed increased pancreatic tumor necrosis factors- α (TNF- α ) and interleukin-1 β (IL-1 β ) levels. A disturbance in oxidative stress markers was evident by elevated pancreatic lipid peroxides (TBARS) and decline in pancreatic antioxidants’ concentrations including reduced glutathione (GSH); superoxide dismutase (SOD); and glutathione peroxidase (GSH-Px). Histological examination confirmed pancreatic injury. Pre-treatment with mesna was able to abolish the changes in pancreatic enzymes, oxidative stress markers (TBARS, SOD, GSH and GSH-Px), pancreatic inflammatory markers (TNF- α , IL-1 β ) as well as histological changes. Conclusions Mesna mitigates AP by alleviating pancreatic oxidative stress damage and inhibiting inflammation.
摘要
背景急性胰腺炎 (Acute pancreatitis,AP) 是一种突发的胰腺炎症性疾病,死亡率高,尤其是在存在全身炎症反应和多器官功能衰竭的情况下。氧化应激已被证明参与急性胰腺炎的病理生理过程。目的探讨美斯纳对雨蛙肽诱导的急性胰腺炎模型的影响。方法动物分为 5 组: 第 1 组为对照组,给予生理盐水; 第 ⅱ 组 (mesna 组) 给予 mesna,剂量为 (100 mg/kg/剂, 我。 p.) 4 次; ⅲ 组 (急性胰腺炎组) 按 (20 µ g/kg/剂量,s.C.) 4 次,间隔 1 h; ⅵ 组,cerulein + mesmesna,按 (100 mg/kg,i.p.) 的剂量给予 mesna 治疗。每次注射雨蛙素前 15 min。结果急性胰腺炎动物血清淀粉酶和脂肪酶水平升高。生化指标显示胰腺肿瘤坏死因子-α (TNF-α) 和 interleukin-1 β (IL-1 β) 水平升高。氧化应激标志物的紊乱明显表现为胰腺脂质过氧化物 (TBARS) 升高,胰腺抗氧化物浓度下降,包括还原型谷胱甘肽 (GSH); 超氧化物歧化酶 (SOD); 和谷胱甘肽过氧化物酶 (GSH-Px)。组织学检查证实为胰腺损伤。Mesna 预处理能够消除胰腺酶、氧化应激标志物 (TBARS 、 SOD 、 GSH 和 GSH-Px) 、胰腺炎症标志物 (TNF-α 、 IL-1 β) 以及组织学改变。结论 Mesna 通过减轻胰腺氧化应激损伤和抑制炎症反应减轻 AP。
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