水飞蓟素对急性胰腺炎大鼠急性肺损伤及MAPK/NF-κB信号通路的影响  

Effect of silymarin on acute lung injury and MAPK/NF-κB signaling pathway in rats with acute pancreatitis

作　　者：陈彩云[1] 许秋霞[1] 张吟[1] 庄奕筠[1] 高雅莉[1] CHEN Cai-yun;XU Qiu-xia;ZHANG Yin;ZHUANG Yi-jun;GAO Ya-li(Dept of Pharmacy, the Second Affiliated Hospital of Fujian Medical University, Quanzhou Fujian 362000, China)

机构地区：[1]福建医科大学附属第二医院药学部,福建泉州362000

出　　处：《中国药理学通报》2019年第2期192-197,共6页Chinese Pharmacological Bulletin

基　　金：福建省科技厅社会发展引导性基金资助项目(No 2015Y0055);福建省卫计委青年科研课题(No 2015-1-60)

摘　　要：目的探究水飞蓟素对急性胰腺炎大鼠急性肺损伤的保护作用,以及与丝裂原活化蛋白激酶(MAPK)/核因子κB(NF-κB)信号通路的关系。方法将SD大鼠分为假手术组、模型组、水飞蓟素低、中、高剂量组(50、100、200 mg·kg^(-1))、地塞米松组(2 mg·kg^(-1)),酶联免疫法测定炎症指标;苏木精-伊红染色法(HE)观察胰腺、肺部组织病理学变化;免疫印迹法检测MAPK/NF-κB通路蛋白表达。结果建模后,模型组PaO_2、OI降低,PaCO_2、胰腺、肺组织病理评分、淀粉酶活性、TNF-α和IL-1β水平均升高,与假手术组相比差异有显著性(P<0.05);给药后,水飞蓟素各组、阳性组的PaO_2、OI升高,PaCO_2、胰腺、肺组织病理评分、淀粉酶活性、TNF-α、IL-1β水平、胰腺、肺组织W/D、PMN降低,p-JNK、p-p38、p-ERK1/2、p-IκBα蛋白表达降低,呈剂量依赖性,与模型组相比差异有显著性(P<0.05)。结论水飞蓟素可能通过抑制MAPK/NF-κB通路,发挥对重症急性胰腺炎大鼠急性肺损伤的保护作用。Aim To explore the protective effect of silymarin on acute lung injury in rats with severe acute pancreatitis and its relationship with mitogen activated protein kinase (MAPK)/nuclear factor κB (NF-κB) signaling pathway. Methods SD rats were divided into sham operation group, model group, silymarin low, medium and high dose group (50, 100, 200 mg·kg^-1 ), and dexamethasone group (2 mg·kg^-1 ). Enzyme-linked immunosorbent assay was used to detect inflammatory markers. Hematoxylin eosin staining (HE) was used to observe the histopathological changes of pancreas and lung. Western blot was used to detect the protein expression of MAPK/NF-κB pathway. Results After modeling, PaO2 and OI decreased, PaCO2, pancreas, lung histopathological score, amylase activity, TNF-α, IL-1β levels all increased in model group, compared with sham operation group, the differences were significant ( P <0.05). After administration of silymarin, PaO2 and OI increased, PaCO2, pancreas, lung histopathological score, amylase activity, TNF-α, IL-1β levels, W/D and PMN in pancreas, lung tissues decreased, p-JNK, p-p38, p-ERK1/2, p-IκBα protein expression decreased in a dose-dependent manner, which was significantly different from those of model group ( P <0.05). Conclusions Silymarin may play a protective role in acute lung injury in rats with severe acute pancreatitis by inhibiting MAPK/NF-κB pathway.

关 键 词：重症急性胰腺炎 胰腺损伤 肺损伤 水飞蓟素 丝裂原活化蛋白激酶 核因子ΚB 

分 类 号：R332[医药卫生—人体生理学] R329.25[医药卫生—基础医学]