Effect of hydroxychloroquine on ventricular remodeling after myocardial infarction in rats
AIM:To investigate the effect of hydroxychloroquine on ventricular remodeling after myocardial infarction (MI) in rats. METHODS: MI and sham-operation were established by Maisel's method. Three days after operation,surviving Sprague-Dawley (SD)rats were divided into MI hydroxychloroquine group ( n = 11,group A),MI placebo group (n =15,group B),sham-operation hydroxychloroquine group (n = 7,group C) and sham-operation placebo group ( n = 7,group D),which were treated with hydroxychloroquine and physiological saline respectively. The mortality rate of each group was calculated after the treatments. Cardiac structure index (IVSd,LVPWd and LVDd)and function index ( FS and EF)were examined by Doppler ultrasonograph and protein expression of P-Akt and P53 around the infarction zones was detected by Western blot. RESULTS: The mortality rate in MI hydroxychloroquine group,MI placebo group,sham-operation hydroxychloroquine group and sham-operation placebo group was 9%,40%,0% and 0% respectively. In MI placebo group,IVSd and LVPWd grew thicker and then became thinner,and LVDd grew bigger,while FS and EF became smaller. In MI hydroxychloroquine group,IVSd and LVPWd grew thicker,and LVDd remained unchanged,while FS and EF grew bigger. Eighty seven days after treatment,IVSd was (0. 11 ±0.01)and (0.12 ± 0.01)cm;LVPWd (0.15 ±0.01) and (0.13 ±0.01 )cm;LVDd (0.64±0.01) and (0. 72 ±0. 01 )cm;FS (29.44 ±2.13)% and (20.39±1.83)%;EF (62.23 ±2.33)% and (47.99 ± 1. 89)%;IOD of P-Akt (1. 12 ±0.21) and (0.58 ±0. 18) (P<0.05), and IOD of P53 ( 1. 01 ± 0. 20) and (0. 98 ± 0. 19) in MI hydroxychloroquine group and MI placebo group. In sham-operation hydroxychloroquine group and sham-operation placebo group,IVSd was (0.13 ±0.01)and (0.12 ±0.01)cm;LVPWd (0. 15 ± 0.01)and (0.14±0.01)cm (P<0.05);LVDd (0.60±0.01) and (0.57 ±0.01)cm;FS (34.33 ±2.13)% and (35.57 ± 1.78)%;EF (69. 82 ±2.91)% and (71.15 ±2.11)%;IOD of P-Akt (0.78±0.20)and (0. 62 ±0.23),and IOD of P53 (0.49± 0.22) and (0.32 ±0.19). CONCLUSION: Hydroxychloroquine prevents ventricle remodeling after MI by modulating the protein expressions and activities of Akt in myocardium.