黏着斑激酶抑制药Y15在中心静脉导管联合5-氟尿嘧啶诱导的血管内皮细胞损伤中的抗炎作用  

Anti-inflammatory effects of focal adhesion kinase inhibitor Y15 on vascular endothelial cell injury induced by central venous catheter combined with 5-fluorouracil

作　　者：王彦茹 常健[5] 蒋萍[3] 冯莺[6] 李青青[1] 赵艳杰 李新霞[4] WANG Yan-ru;CHANG Jian;JIANG Ping;FENG Ying;LI Qing-qing;ZHAO Yan-jie;LI Xin-xia(School of Nursing,Zhejiang Chinese Medical Unitersiy,Hangzhou 310053,Zhejiang Prorince,China;School of Nursing,Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;School of Basic Medicine,Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;College of Pharmacy,Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;Department of Nursing,Shanghai General Hospital,Shanghai 201620,China;Department of Nursing,Hangzhou Hospial of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang Prouince,China)

机构地区：[1]浙江中医药大学护理学院,浙江杭州310053 [2]新疆医科大学护理学院,新疆维吾尔自治区乌鲁木齐830011 [3]新疆医科大学基础医学院,新疆维吾尔自治区乌鲁木齐830011 [4]新疆医科大学药学院,新疆维吾尔自治区乌鲁木齐830011 [5]上海市第一人民医院护理部,上海201620 [6]杭州市中医院护理部,浙江杭州310007

出　　处：《中国临床药理学杂志》2022年第20期2449-2453,共5页The Chinese Journal of Clinical Pharmacology

基　　金：新疆维吾尔自治区自然科学基金资助项目(2020D01C150);新疆乌鲁木齐市科技局应用开发计划基金资助项目(H161318002)。

摘　　要：目的研究黏着斑激酶(focal adhesion kinase,FAK)抑制药(Y15)对中心静脉导管(central venous catheter,CVC)联合5-氟尿嘧啶(5-fluorouracil,5-FU)诱导的血管内皮细胞损伤的抗炎作用及其机制。方法将EA.hy926细胞随机分为正常对照组、模型组和实验组。正常对照组用10%胎牛血清的DMEM高糖完全培养基2 mL培养细胞,无其他干预措施;模型组是用3道划痕(每道2 cm)、留置的3根CVC(1 cm)节断和1 mg·mL^(-1)5-FU 80μL共同诱导的细胞炎性损伤模型;模型组中加入2 mmol·L^(-1)Y1550μL,即为实验组。用实时荧光定量聚合酶链反应检测白细胞介素-6(interleulcin 6,IL-6)mRNA的表达水平,用蛋白质印迹法检测磷酸化黏着斑激酶Y397(phosphorylated focal adhesion kinase Y397,pY397 FAK)和核因子κB(nuclear factor kappa B,NF-κB)的表达水平。结果干预48 h后,正常对照组、模型组和实验组的IL-6 mRNA表达水平分别为1.07±0.11,5.34±0.65和1.58±0.13,pY397 FAK相对表达水平分别为0.20±0.04,1.27±0.04和0.74±0.03,NF-κB相对表达水平分别为0.32±0.02,1.72±0.07和1.05±0.14。实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.001)。结论FAK抑制药Y15通过调节FAK-NF-κB信号通路对CVC联合5-FU诱导的EA.hy926细胞损伤产生抗炎作用。Objective To explore the anti-inflammatory effects of focal adhesion kinase(FAK)inhibitor(Y15)on vascular endothelial cell injury induced by central venous catheter(CVC)combined with 5-fluorouracil(5-FU)and its mechanism.Methods EA.hy926 cells were randomly divided into normal control group,model group and experimental group.Normal control group was cultured with 2 mL of DMEM high glucose complete medium containing 10%fetal bovine serum,without other interventions.Model group was a cell inflammatory injury model induced by 3 scratches(2 cm each),3 CVC(1 cm)segments and 1 mg·mL^(-1)5-FU 80μL.2 mmol·L^(-1)Y1550μL was added to the model group to form the experimental group.The mRNA level of interleukin 6(IL-6)was measured via real-time fluorescence quantitative polymerase chain reaction.Western blotting was used to detect the expression levels of phosphorylated focal adhesion kinase Y397(p Y397 FAK)and nuclear factor kappa B(NF-κB)in EA.hy926 cells.Results After treatment 48 hours,the levels of IL-6m RNA in the normal control,model and experimental groups were 1.07±0.11,5.34±0.65 and 1.58±0.13;the relative expression levels of p Y397 FAK were 0.20±0.04,1.27±0.04 and 0.74±0.03;the relative expression levels of NF-κB were 0.32±0.02,1.72±0.07 and 1.05±0.14,respectively.The above indexes in the experimental group were compared with those in model group,and the differences were statistically significant(all P<0.001).Conclusion FAK inhibitor Y15 have anti-inflammatory effects on EA.hy926 cell damage induced by CVC combined with 5-FU by regulating the FAK-NF-κB signaling pathway.

关 键 词：黏着斑激酶抑制药 中心静脉导管 5-氟尿嘧啶 EA.hy926细胞 炎症反应 黏着斑激酶-核因子κB信号通路 

分 类 号：R97[医药卫生—药品]