Protective Effects of Fucoidan, a P- and L-Selectin Inhibitor, in Murine Acute Pancreatitis
Protective Effects of Fucoidan, a P- and L-Selectin Inhibitor, in Murine Acute Pancreatitis
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DOI：
10.1097/mpa.0b013e3182a63b9d
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发表时间：
2014-01-01
期刊：
影响因子：
2.9
通讯作者：
de Souza, Marcellus H. L. P.
中科院分区：
文献类型：
--
作者：
Carvalho, Ana C. S.;Sousa, Rhamon B.;de Souza, Marcellus H. L. P.
目的探讨L-和P-选择素调节剂褐藻糖胶（fucoidan）对2种急性胰腺炎小鼠模型的保护作用。实验组在胰腺炎诱导前接受岩藻依聚糖（25 mg/kg，静脉注射），而对照组仅接受生理盐水。24小时后检测血清淀粉酶、脂肪酶、白细胞介素1（IL-1）、肿瘤坏死因子（TNF-α）和亚硝酸盐。结果与对照组相比，急性胰腺炎牛磺石胆酸组和蛙皮素组血清淀粉酶、脂肪酶、亚硝酸盐、TNF-α、IL-1、胰腺和肺髓过氧化物酶（MPO）活性均升高。褐藻糖胶显着降低了淀粉酶，脂肪酶，胰腺和肺MPO，TNF-α，IL-1，和亚硝酸盐在两种模型中的水平增加。在两种急性胰腺炎模型中观察到的胰腺组织学变化显着衰减褐藻糖胶。结论褐藻糖胶通过减少中性粒细胞浸润和全身炎症减轻小鼠急性胰腺炎的严重程度，表明选择素的调制可能构成一个有前途的治疗方法。
Objective The objective of this study was to investigate the potential protective effects of fucoidan, an L- and P-selectin modulator, in 2 murine models of acute pancreatitis.Methods Acute pancreatitis was induced in mice either by the retrograde infusion of taurolithocholic acid sulfate into the pancreatic duct or by intraperitoneal injections of cerulein (50 g/kg per hour). The experimental groups received fucoidan (25 mg/kg, intravenously) before pancreatitis induction, whereas control groups received only saline. After 24 hours, serum amylase, lipase, interleukin 1 (IL-1), tumor necrosis factor (TNF-), and nitrite were measured. In addition, myeloperoxidase (MPO) activity (lung and pancreas) and histological assessment (pancreas) were determined.Results Serum amylase, lipase, nitrite, TNF-, and IL-1, and pancreatic and lung MPO were increased in both taurolithocholic acid sulfate and cerulein acute pancreatitis compared with the respective control groups. Fucoidan significantly decreased the augmented levels of amylase, lipase, pancreatic and lung MPO, TNF-, IL-1, and nitrite in both models. Pancreas histological changes observed in both acute pancreatitis models were significantly attenuated by fucoidan.Conclusions Fucoidan reduced the severity of acute pancreatitis in mice by decreasing neutrophil infiltration and systemic inflammation, suggesting that modulation of selectins may constitute a promising therapeutic approach.