羟氯喹对心肌梗死后心室重塑的影响

Effect of hydroxychloroquine on ventricular remodeling after myocardial infarction in rats

目的:探讨羟氯喹对心肌梗死后心室重塑的影响.方法:按Maisel方法建立心肌梗死与假手术模型,将术后3d仍存活的SD大鼠按不同干预条件再分为心肌梗死羟氯喹组(n=11,A组),心肌梗死安慰剂组(n=15,B组),假手术羟氯喹组(n=7,C组),假手术安慰剂组(n=7,D组).计算术后3～87d各组死亡率.多普勒超声仪测定心脏结构指标舒张末期室间隔厚度(IVSd),舒张末期左室后壁厚度(LVPWd),左室舒张末期内径(LVDd)和功能指标短轴缩短率(FS),射血分数(EF).WesternBlot测定心肌梗死周边组织P-Akt,P53蛋白表达.结果:A,B,C,D各组死亡率分别为9%,40%,0%,0%.B组IVSd,LVPWd先变厚尔后逐渐变薄,LVDd逐渐变大,FS,EF逐渐下降;A组IVSd,LVPWd逐渐变厚,LVDd无明显变化,FS,EF逐渐升高.术后87d,A组与B组IVSd分别为(0.11±0.01),(0.12±0.01)cm;LVPWd分别为(0.15±0.01),(0.13±0.01)cm;LVDd分别为(0.64±0.01),(0.72±0.01)cm;FS分别为(29.44±2.13)%,(20.39±1.83)%;EF分别为(62.23±2.33)%,(47.99±1.89)%;P-Akt蛋白IOD分别为(1.12±0.21),(0.58±0.18)(P均<0.05),而2组间P53蛋白IOD差异无统计学意义.C组与D组IVSd分别为(0.13±0.01),(0.12±0.01)cm;LVPWd分别为(0.15±0.01),(0.14±0.01)cm(P均<0.05);LVDd分别为(0.60±0.01),(0.57±0.01)cm;FS分别为(34.33±2.13)%,(35.57±1.78)%;EF分别为(69.82±2.91)%,(71.15±2.11)%;P-Akt蛋白IOD分别为(0.78±0.20),(0.62±0.23);P53蛋白IOD分别为(0.49±0.22),(0.32±0.19).结论:羟氯喹可通过调控心肌Akt蛋白表达及活性,明显改善心肌梗死后心室重塑.

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.