Pharmacological postconditioning with lactic acid and low dose edaravone could attenuate myocardial reperfusion injury through mitochondrial pathway
10.3760/cma.j.issn.0253-3758.2013.08.005
- VernacularTitle:乳酸和低剂量依达拉奉联合药物后适应通过线粒体途径减轻大鼠心肌缺血再灌注损伤
- Author:
Guo-Ming ZHANG
1
;
Yu WANG
;
Xiao-Yan LI
;
Lin XU
;
Yuan-Yuan SUN
;
Yu-Zhen LI
;
Li-Feng LIU
Author Information
1. 250031,济南军区总医院心内科
- Keywords:
Myocardial reperfusion injury;
Mitochondria,heart;
Lactic acid;
Free radical scavengers
- From:
Chinese Journal of Cardiology
2013;41(8):647-653
- CountryChina
- Language:Chinese
-
Abstract:
Objective To test the hypothesis that pharmacological postconditioning with lactic acid and low dose edaravone could mimic the upper trigger of mechanical postconditioning and relieve reperfusion injury through mitochondrial pathway.Methods Rats were randomly divided into 6 groups (n =18 each):sham,reperfusion/injury (I/R),postconditioning (IP),lactic acid (Lac,60 μl),low dose edaravone (Eda,3 μg/kg),and Lac + Eda.After 45 min myocardial ischemia,different drugs or saline were administrated around the infarct border according to different groups using micro syringe at the time of reperfusion.After 10 min reperfusion,right atrial plasma pH value was determined in all rats.Then the rats were sacrificed at 1,6 and 24 h (n =6 each),apoptotic index was measured by TUNEL,infarct area and ischemic area were measured through Evans blue-TTC double staining,mitochondrial absorbance,the contents of MDA and SOD in ischemic myocardium were detected by spectrophotometry,and the expression of apoptotic pathway molecules,such as Bcl-2,Bax and Cytochrome c (Cyt-c),were detected by Western blot.Results Right atrial plasma pH value was significantly lower,the content of MDA was significantly lower,and the content of SOD was significantly higher in IP and Lac + Eda groups than in I/R group (all P ＜ 0.05).The mitochondrial absorbance in Lac + Eda group at all time points were all significantly higher than those in I/R group (all P ＜ 0.05).The level of Bcl-2 in ischemic myocardium in Lac + Eda group was significantly higher than in I/R group (1.02 ±0.19 vs.0.02 ±0.01,P ＜0.05),the level of Bax (0.38 ±0.07 vs.2.40 ± 0.45,P ＜ 0.05) and Cyt-c (0.78 ± 0.05 vs.6.54 ± 1.86,P ＜ 0.05) were all lower than those in I/R group.The content of CK[(849 ±228) vs.(1249 ±211) U/L,P ＜0.05] and CK-MB [(470 ±266) vs.(966 ±263) U/L,P ＜0.05] in Lac + Eda group were all significantly lower than in I/R group,apoptotic index [(10.51 ±1.52)％ vs.(15.00±1.90)％,P＜0.05] and infarct area [(27.12±5.55) ％ vs.(45.66 ± 10.81) ％,P ＜ 0.05] in Lac + Eda group were all significantly lower than those in I/R group.Conclusion Pharmacological postconditioning with lactic acid and low dose edaravone could mimic the upper triggers of mechanical postconditioning and attenuate myocardial reperfusion injury through mitochondrial pathway.
