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毛蕊异黄酮通过抑制 p38 MAPK 和 NF-κB 信号通路减轻小鼠雨蛙肽诱导的急性胰腺炎的炎症反应和氧化应激。

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.

机构信息

Department of Gastroenterology, Jining No.1 People's Hospital, Jining, 272011, PR China.

Department of Clinical Pharmacy, Jining No.1 People's Hospital, Jining, 272011, PR China.

出版信息

Biomed Pharmacother. 2018 Sep;105:599-605. doi: 10.1016/j.biopha.2018.05.080. Epub 2018 Jun 8.

Abstract

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 μg/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)-α, interleukin (IL)-6, and IL-1β 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-κB/p65 and phosphorylation of the inhibitor of NF-κB (IκBα) 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-κB signal pathways. Calycosin's benefits for AP patients need to be explored further.

摘要

急性胰腺炎(AP)是一种常见的急性腹部疾病,伴有全身炎症反应综合征,甚至可能并发多器官损伤。本研究旨在探讨具有抗氧化和抗炎活性的黄芪异黄酮毛蕊异黄酮是否可以预防胆酸钠诱导的 AP。为此,Balb/C 小鼠注射胆酸钠(50μg/kg)建立 AP 动物模型。在第一次胆酸钠注射前 1 小时给予毛蕊异黄酮(25 和 50mg/kg,po)。最后一次胆酸钠注射后,处死小鼠并取血进行细胞因子分析。取出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。毛蕊异黄酮治疗可逆转 AP 小鼠血清淀粉酶和脂肪酶水平的升高,减轻胰腺的病理损伤,降低 TNF-α、IL-6 和 IL-1β的水平。此外,毛蕊异黄酮可显著减轻胆酸钠诱导的胰腺水肿,抑制 MPO 活性,增加超氧化物歧化酶(SOD)活性,并抑制 NF-κB/p65 的表达和 NF-κB 抑制剂(IκBα)和 p38 MAPK 的磷酸化。这些结果表明,毛蕊异黄酮通过 p38 MAPK 和 NF-κB 信号通路发挥抗炎和抗氧化应激作用,从而保护 AP。需要进一步探索毛蕊异黄酮对 AP 患者的益处。

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