灯盏乙素对心肌缺血/再灌注损伤的保护作用及机制  

Protective effect of scutellarin on myocardial ischemia/reperfusion injury and its mechanism

作　　者：季宇彬 马晓玉 陈荣昌[2] 杨龙坡 孙桂波[2] 孙晓波[2] JI Yu-bin;MA Xiao-yu;CHEN Rong-chang;YANG Long-po;SUN Gui-bo;SUN Xiao-bo(Research Center on Pharmaceutical Engineering Technology,Harbin University of Commerce,Harbin150076,China;Pharmacology and Toxicology Center,Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences,Beijing100094,China)

机构地区：[1]哈尔滨商业大学药物工程技术研究中心,黑龙江哈尔滨150076 [2]中国医学科学院北京协和医学院药用植物研究所药理毒理中心,北京100094

出　　处：《中国药理学通报》2019年第5期648-653,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年基金项目(No 81603334);协和青年基金和中央高校基本科研业务费专项资金资助项目(No 3332016070)

摘　　要：目的研究灯盏乙素对大鼠离体心脏缺血/再灌注损伤的保护作用及机制。方法 SD大鼠随机分为空白组、模型组、灯盏乙素低、中、高剂量组(0.3、3、30 mg·kg^(-1)),预给药7 d,应用Langendorff离体灌流大鼠心脏复制急性心肌缺血/再灌注损伤模型。离体灌注时,给药组用含灯盏乙素的K-H液进行灌流(0. 3、3、30 mg·L^(-1))。记录心肌收缩功能;试剂盒检测大鼠心肌组织中AST、CK、LDH的活性; ELISA检测炎性因子ICAM-1、IL-1β、IL-6、IL-18、TNF-α的含量; HE染色观察心肌组织形态学的改变; Western blot检测IL-1β、NLRP3、NF-кB相关蛋白表达。结果与空白组相比,模型组大鼠离体心脏收缩功能明显降低,心肌组织AST、CK、LDH活性明显升高,ICAM-1、IL-1β、IL-6、IL-18、TNF-α等炎性因子的含量明显升高,IL-1β、NLRP3蛋白表达水平及NF-кB核转位明显升高。灯盏乙素能明显改善上述病理改变。结论灯盏乙素对心肌缺血/再灌注损伤的保护作用可能与抑制NF-кB/NLRP3/IL-1β通路有关。Aim To study the protective effect of scutellarin (Scu) on ischemia/reperfusion (I/R) injury in isolated rat hearts and its mechanism. Methods Acute myocardial I/R injury was induced by Langendorff perfusion in isolated rat hearts.SD rats were randomly divided into five groups: blank group,model group,low,medium and high dose group of Scu (0.3,3,30 mg·kg-1 ).The drug experimental group was perfused with K-H solution containing Scu (0.3,3,30 mg·L-1 ) in vitro perfusion.Myocardial contractile function was recorded;AST,CK and LDH activities in rat myocardium were detected by kit;ICAM-1,IL-1β,IL-6,IL-18 and TNF-α were detected by ELISA;the morphological changes of myocardium were observed by HE staining;and the expressions of IL-1β,NLRP3 and NF-кB were detected by Western blot. Results Compared with blank group,the contractile function of isolated rat heart in model group significantly decreased,the activities of AST,CK and LDH in myocardium significantly increased,and the contents of inflammatory factors such as ICAM-1,IL-1β,IL-6,IL-18 and TNF-α significantly increased.The expression of IL-1β and NLRP3 and the nuclear translocation of NF-кB significantly increased.Scu significantly improved the above pathological changes. Conclusion The protective effect of Scu on myocardial I/R injury may be related to the inhibition of NF-кB/NLRP3/IL-1β pathway.

关 键 词：灯盏乙素 大鼠 心肌缺血/再灌注 炎症 NF-κB NLRP3 

分 类 号：R-332[医药卫生] R284.1