Effects and potential mechanisms of short-term use of simvastatin on myocardial no-reflow after ischemia-reperfusion in rats
10.3321/j.issn:0253-3758.2008.08.014
- VernacularTitle:短期应用辛伐他汀对大鼠缺血再灌注后心肌无复流的影响及其潜在机制
- Author:
Yan-Hong LIU
1
;
Mei ZHANG
;
Ling-Mei LIU
;
Xin ZHOU
;
Zhan-Quan JIAO
;
Yu-Ming LI
;
Wei PANG
Author Information
1. 天津市第三中心医院
- Keywords:
Myocardial reperfusion injury;
Endothelium,vascular;
Simvastatin
- From:
Chinese Journal of Cardiology
2008;36(8):729-734
- CountryChina
- Language:Chinese
-
Abstract:
Objective The main objective of this study is to assess the the effect of simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential mechanisms. Methods Adult male Wistar rats were randomized into sham group (n = 12 ), L/R (90 min ischemia via coronary ligntion/120 min reperfusion, n = 18) and I/R plus sim group (20 mg · kg-1·d-1 sim pretreated via garage beginning 3 days before I/R, n = 18). After reperfusion, area at risk/area of left ventricular ( RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at risk (NA/RA) and area of myocardial infarction/area at risk (MLA/RA) were measured. Myocardium homogenate was used to determine the activity of Enos,Inos and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was performed to determine the positive index of NF-Кb p65 in cardiomyocytes and arteriole. Results The NR and myocardial infarction areas in I/R plus sim group were significantly smaller than those in I/R group (34. 10±7. 05 vs. 52. 09±6. 89, 78. 80±7. 60 vs. 90. 13±5.72, each P <0. 05) while the ischemia area was similar between the 2 groups (P 0. 05). The myocardial activities of Inos and MPO, the contents of NO and MDA were significantly lower while Enos activity was significantly higher in I/R plus sim group than those in I/R group (5. 02±1.64 vs. 9. 19±2. 89, 586. 21±126. 97 vs. 744. 49±137.53, 257.72± 93.43 vs. 384. 10±40. 68, 72. 10±18.56 vs. 111.84±38. 58, 7. 08±1.74 vs. 3.72±0. 98, all P < 0. 05). The positive index of NF-Кb p65 in cardiocytes and arteriole at left ventricular wall near the area of myocardial infarction was significantly lower in I/R plus sim group than that in I/R group (21.59±10. 5 vs. 34. 32±9. 55, 27.27±13.19 vs. 44. 91±15.06, each P < 0. 05). Conclusion Simvastatin could improve myocardial NR after ischemia-reperfusion by attenuating endothelial dysfunction and inhibiting inflammation and neutrophil activation.
