부산대학교 도서관

Background The effects of atorvastatin on SDF-1[alpha] expression under acute myocardial infarction (AMI) are still unclear. Therefore, our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1[alpha] expression in rats with AMI. Methods Male Sprague-Dawley rats were underwent permanent coronary artery ligation and randomly assigned into four groups as follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME), and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d body weight) was administrated by gavage to rats in three atorvastatin treated groups, and L-NAME (40mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively. Results Comparing with group B, NO production, SDF-1[alpha] and CXCR4 expression were significantly up-regulated in three atorvastatin treated groups at the seventh day. However, the increments of SDF-1[alpha] and CXCR4 expression in group A+L-NAME were reduced when NO production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects of atorvastatin were offset either by decrease of SDF-1[alpha] and CXCR4 expression (by L-NAME) or blockage of SDF-1[alpha] coupling with CXCR4 (by AMD3100). Expression of STAT3, a cardioprotective factor mediating SDF-1[alpha]/CXCR4 axis induced cardiac protection, was up-regulated most significantly in group A. The effects of atorvastatin therapy on cardiac function were also abrogated either when SDF-1[alpha] and CXCR4 expression was diminished or the coupling of SDF-1[alpha] with CXCR4 was blocked. Conclusion SDF-1[alpha] upregulation by atorvastatin in rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF-1[alpha] upregulation and SDF-1[alpha] coupling with CXCR4 conferred anti-inflammatory and anti-apoptotic effects under AMI setting which we speculated that ultimately contributed to cardiac function improvement. Keywords: Acute myocardial infarction, Atorvastatin, Stromal cell derived factor-1alpha
Author(s): Ruofeng Qiu[sup.1] , Anping Cai[sup.2] , Yugang Dong[sup.1] , Yingling Zhou[sup.2] , Danqing Yu[sup.2] , Yuli Huang[sup.1] , Dongdan Zheng[sup.1] , Shaoqi Rao[sup.3] , Yingqing Feng[sup.2] and Weiyi Mai[sup.1] [...]