Cardioprotection of Ginkgolide B on Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Regulation of A20-NF-kappa B Pathway
作者
Zhang, R;Xu, L;Zhang, D;Hu, B;Luo, Q;Han, D;Li, JB;Shen, CW
作者单位
[Zhang, Rui; Luo, Qi; Shen, Chengwu] Shandong Univ, Shandong Prov Hosp, Dept Pharm, Jinan, Shandong, Peoples R China.;-;[Xu, Lin] Shandong Univ, Shandong Prov Hosp, Dept Thorac Surg, Jinan, Shandong, Peoples R China.;-;[Zhang, Dong] Shandong Univ, Shandong Prov Hosp, Dept Urol, Jinan, Shandong, Peoples R China.;-;[Hu, Bo] Shandong Univ, Shandong Prov Hosp, Minimally Invas Urol Ctr, Jinan, Shandong, Peoples R China.;-;[Han, Dan] Nanjing Univ, Sch Med, Affiliated Hosp, Dept Pharm,Nanjing Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China.;-;[Li, Jiangbing] Shandong Univ, Shandong Prov Hosp, Dept Cardiol, Jinan, Shandong, Peoples R China.
摘要
Inflammation urges most of the characteristics of plaques involved in the pathogenesis of myocardial ischemia/reperfusion injury (MI/RI). In addition, inflammatory signaling pathways not only mediate the properties of plaques that precipitate ischemia/reperfusion (I/R) but also influence the clinical consequences of the post-infarction remodeling and heart failure. Here, we studied whether Ginkgolide B (GB), an effective anti-inflammatory monomer, improved MI/RI via suppression of inflammation. Left anterior descending (LAD) coronary artery induced ischemia/reperfusion (I/R) of rats or A20 silencing mice, as well as hypoxia/reoxygenation (H/R) induced damages of primary cultured rat neonatal ventricular myocytes or A20 silencing ventricular myocytes, respectively, served as MI/RI model in vivo and in vitro to discuss the anti-I/R injury properties of GB. We found that GB significantly alleviated the symptoms of MI/RI evidently by reducing infarct size, preventing ultrastructural changes of myocardium, depressing Polymorphonuclears (PMNs) infiltration, lessening histopathological damage and suppressing the excessive inflammation. Further study demonstrated that GB remarkably inhibited NF-kappa B p65 subunit translocation, I kappa B-alpha phosphorylation, IKK-beta activity, as well as the downstream inflammatory cytokines and proteins expressions via zinc finger protein A20. In conclusion, GB could alleviate MI/RI-induced inflammatory response through A20-NF-kappa B signal pathway, which may give us new insights into the preventive strategies for MI/RI disease.
关键词
NF-KAPPA-B; REPERFUSION INJURY; TNF-ALPHA; INHIBITION; ACTIVATION; PROMOTES; A20; INFARCTION; ISCHEMIA; PROTECTS
基本信息
