中国免疫学杂志2023，Vol.39Issue(12)：2501-2506,2512,7.DOI:10.3969/j.issn.1000-484X.2023.12.007
环孢素A减轻急性胰腺炎模型小鼠心脏损伤的机制研究
Mechanistic study of Cyclosporin A in alleviating cardiac injury in model mice with acute pancreatitis
摘要
Abstract
Objective:To observe whether Cyclosporin A(CSA)treatment may protect acute pancreatitis(AP)mice and related cardiac injury by consequent attenuation of systemic inflammation via regulating macrophage polarization.Methods:RAW264.7 cells were used for in vitro experiments,stimulated with 0,5,10 and 20 nmol/L CSA for 24 hours,and M2 markers were detected by flow cytometry.C57BL/6J mice were used for experiments in vivo.The mice were randomly divided into 3 groups(n=15):control group,AP model group(intraperitoneal injection of L-arginine)and AP+CSA(20 mg/kg)group,CSA was administered in a pre-treated manner.ELISA kit was used to detect the indexes of pancreatic and myocardial injury in mice;HE staining was used to detect the pathological changes of pancreas and heart tissue;TUNEL method was used to detect apoptosis in tissue sections;CETSA was used to determine the relationship between CSA and PKM;The expressions of PKM2,HIF1α,p-STAT1 and p-STAT6 were detected by Western blot.Results:CSA increased the number of M2 macrophages and decreased the number of M1 macrophages in a dose-dependent manner in vitro.CSA pretreatment significantly improved pancreatic structure and myocardial injury in AP mice,decreased pancreatic histopathological score and serum amylase,lipase,TNF-α,CK-MB,LDH and cTnT levels.CSA pretreatment significantly reduced the number of TUNEL positive cells in myocardium of AP mice.Flow cytometry analysis showed that CSA pretreatment significantly inhibited the proportion of CD11c+F4/80+ and promoted the ratio of CD206+F4/80+ in AP induced myocardial macrophages.CETSA analysis showed that PKM2 was the target of CSA.Conclusion:CSA can significantly improve the severity of L-arginine-induced cardiac damage in AP model mice,and its mechanism of action is related to increasing the number of M2 macro-phages and inhibiting the production of proinflammatory cytokines.关键词
环孢素A/巨噬细胞/极化/急性胰腺炎/心脏损伤Key words
Cyclosporin A/Macrophage/Polarization/Acute pancreatitis/Cardiac injury分类
医药卫生引用本文复制引用
吴童,高雪飞,贾迎丽,杨静..环孢素A减轻急性胰腺炎模型小鼠心脏损伤的机制研究[J].中国免疫学杂志,2023,39(12):2501-2506,2512,7.基金项目
本文为河北省卫生厅科研基金项目(20201495). （20201495）
