Calycosin alleviates cerulein-induced acute pancreatitis by inhibiting the inflammatory response and oxidative stress via the p38 MAPK and NF-κB signal pathways in mice
Calycosin alleviates cerulein-induced acute pancreatitis by inhibiting the inflammatory response and oxidative stress via the p38 MAPK and NF-κB signal pathways in mice
复制标题
DOI：
10.1016/j.biopha.2018.05.080
复制
发表时间：
2018-09-01
影响因子：
7.5
通讯作者：
Wang, Fulai
中科院分区：
文献类型：
--
作者：
Ma, Ran;Yuan, Fang;Wang, Fulai
急性胰腺炎（AP）是一种常见的伴有全身性炎症反应综合征的急性腹部疾病，甚至可并发多器官损害。从黄芪中分离出一种具有抗氧化和抗炎活性的异黄酮——毛蕊异黄酮（calycosin），目的是研究其是否具有抗蓝蛋白诱导的AP作用。为此，我们给Balb/C小鼠注射毛蕊蛋白（50 μ g/kg），建立AP动物模型。在第一次注射毛蕊蛋白前1 h给药毛蕊异黄酮（25和50 mg/kg， p.o）。最后一次注射蓝蛋白后，处死小鼠，取血进行细胞因子分析。切除胰腺进行形态学检查、髓过氧化物酶（MPO）和丙二醛（MDA）分析、免疫组织化学和western blot分析。Calycosin治疗逆转了AP小鼠血清淀粉酶和脂肪酶升高的水平，减轻了胰腺的病理损伤，降低了肿瘤坏死因子(TNF)- α、白细胞介素(IL)-6和IL-1 β的水平。此外，Calycosin显著减轻了cerulein诱导的胰腺水肿，抑制了MPO活性，增加了超氧化物歧化酶（SOD）活性。抑制NF-kappa B/p65的表达和NF-kappa B抑制剂（I kappa B α）和p38 MAPK的磷酸化。这些结果表明，毛蕊异黄酮通过p38 MAPK和NF-kappa B信号通路发挥抗炎和抗氧化应激作用。毛蕊异黄酮对AP患者的益处有待进一步探讨。
Acute pancreatitis (AP) is a common acute abdominal disease accompanied by systemic inflammatory response syndrome, and could even be complicated by multiple-organ damage. This study aimed to examine whether calycosin, an isoflavone isolated from Radix astragali with antioxidant and anti-inflammatory activity, could protect against AP induced by cerulein. To this end, Balb/C mice were injected with cerulein (50 mu g/kg) to establish the animal model of AP. Calycosin (25 and 50 mg/kg, p.o.) was administered 1 h prior to the first cerulein injection. After the last injection of cerulein, the mice were sacrificed and blood was obtained for cytokine analysis. The pancreas was removed for morphological examination, myeloperoxidase (MPO) and malondialdehyde (MDA) analyses, immunohistochemistry, and western blot analysis. Calycosin treatment reversed the increased serum levels of amylase and lipase, alleviated the pathological damage in the pancreas, and decreased the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1 beta in mice with AP. Additionally, calycosin significantly reduced cerulein-induced pancreatic edema, inhibited MPO activity and increased superoxide dismutase (SOD) activity, and inhibited the expression of NF-kappa B/p65 and phosphorylation of the inhibitor of NF-kappa B (I kappa B alpha) and p38 MAPK. These results suggested that calycosin protects against AP by exerting anti-inflammatory and anti-oxidative stress effects via the p38 MAPK and NF-kappa B signal pathways. Calycosin's benefits for AP patients need to be explored further.