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目的观察钙激活蛋白酶Ⅰ(calpain Ⅰ)抑制剂对长期心房快速起搏致心房颤动犬的心房结构重构的影响。方法杂种犬15只,分为假手术组、起搏组、抑制剂组各5只。于犬右心耳缝置电极,起搏3周(600次/min)。起搏后抑制剂组每日给以 calpain Ⅰ抑制剂 N-Acetyl-Leu-Leu-Met(ALLM)1.0 mg·kg~(-1)·d~(-1)静脉注射,起搏组和假手术组给予等量溶剂二甲亚砜。采用荧光光度法测定心房肌 calpain Ⅰ活性,光镜观察肌溶解程度,电镜观察超微结构的变化,Western blot 技术测定心肌肌钙蛋白 T 蛋白含量,超声测定左心房容积的变化。结果起搏3周后,起搏组 calpain Ⅰ活性增加至假手术组的2.3倍(P<0.01),抑制剂组 calpain Ⅰ活性为假手术组的1.1倍(P>0.05);起搏组左心房肌溶解的比率为(76.7±5.9)%,抑制剂组左心房肌溶解的比率为(20.8±8.1)%,两组比较,P<0.01。calpain Ⅰ活性与肌溶解的比率呈高度正相关(r=0.89)。肌钙蛋白 T 蛋白含量在抑制剂组高于起搏组(P<0.01)。抑制剂组左心房容积的变化较起搏组显著减轻。结论 ALLM 通过抑制心房快速起搏犬心肌 calpain Ⅰ活性,防止了心房肌结构的改变,为心房颤动后心肌的保护提供了一种可能的有效途径。
Objective To investigate the effect of calpain Ⅰ inhibitor on atrial structural remodeling in atrial fibrillation dogs with chronic atrial pacing. Methods 15 dogs were divided into sham operation group, pacing group and inhibitor group. Right electrode in the dog suture electrode, pacing for 3 weeks (600 beats / min). The rats in the pacing group were injected with 1.0 mg · kg -1 (-1) calpain Ⅰ inhibitor of N-Acetyl-Leu-Leu-Met (ALLM) The operation group was given the same amount of solvent dimethyl sulfoxide. The activity of calpain Ⅰ in atrial myocardium was determined by fluorescence spectrophotometry. The degree of myosin staining was observed with light microscope. The ultrastructure was observed with electron microscopy. The content of cardiac troponin T protein was determined by Western blot and the left atrium volume was measured by ultrasound. Results After 3 weeks of pacing, the activity of calpain Ⅰ in pacing group was increased 2.3 times (P <0.01), and the activity of calpain Ⅰ in inhibitor group was 1.1 times that of sham group (P> 0.05) The rate of atrial lysis was (76.7 ± 5.9)% in the inhibitor group and (20.8 ± 8.1)% in the inhibitor group, P <0.01. The ratio of calpain I activity to muscle lysis was highly positively correlated (r = 0.89). Troponin T protein levels in the inhibitor group were higher than those in the pacing group (P <0.01). Left atrial volume changes in the inhibitor group were significantly reduced compared with those in the pacing group. Conclusion ALLM can prevent the atrial myocardium from changing rapidly by inhibiting the activity of calpain Ⅰ in canine atrial pacing rapidly and provide a possible and effective way to protect myocardium after atrial fibrillation.