Li Wei-min, Xue Hong-jie, Li Yue, Zhang Li, Gong Yong-tai, Sheng Li, Chu Shan
Department of Cardiology, The First Clinical Hospital of Harbin Medical University, Harbin 150001, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2007 Feb;35(2):132-6.
To study the relation of the structural remodeling processes and activation of calpain I.
Fifteen dogs were randomly divided into three groups. The dogs in pacing group (n=5) and inhibitor group (n=5) were subjected to 3 weeks of rapid atrial pacing at 600 beats/min, control dogs (n=5) were in sham-operated group. The dogs in inhibitor group were administered intravenous N-Acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, and in pacing group and sham-operated group were administered intravenous DMSO. The activity of calpain I was measured by hydrolyzing Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. The ultrastructure of atrium was examined by light and electron microscopy. TnT expression was assessed by Western blot. Echocardiography examination was performed in all the three groups.
Calpain I activity was significantly increased in pacing group (2.3-fold, P<0.01), and decreased in inhibitor group (1.1-fold, P>0.05), compared to sham-operated group respectively. The percentages of myolysis were (76.7 +/- 5.9)% and (20.8 +/- 8.1)% in pacing group and inhibitor group respectively (P<0.01). TnT expression decreased in the rapid pacing-induced persistent atrial fibrillation, and these effects were inhibited by calpain I inhibitor ALLM. The area and volume of left atrium tended to increase after 3 weeks ALLM treatment in inhibitor group, but the change was not as prominent as in pacing group (P<0.05).
ALLM can decrease calpain I activity, and prevent canine atrial cardiomyocyte structural remodeling during atrial fibrillation. This study provided a capacity of atrial cardiomyocyte protection.
研究结构重塑过程与钙蛋白酶I激活之间的关系。
将15只犬随机分为三组。起搏组（n = 5）和抑制剂组（n = 5）的犬接受为期3周的600次/分钟快速心房起搏，对照组犬（n = 5）为假手术组。抑制剂组的犬静脉注射钙蛋白酶抑制剂N - 乙酰 - 亮氨酰 - 亮氨酰 - 甲硫氨酸（ALLM），起搏组和假手术组静脉注射二甲基亚砜。通过水解琥珀酰 - 亮氨酰 - 亮氨酰 - 缬氨酰 - 酪氨酸 - 7 - 氨基 - 4 - 甲基香豆素测定钙蛋白酶I的活性。用光镜和电镜检查心房的超微结构。通过蛋白质印迹法评估肌钙蛋白T（TnT）的表达。对三组均进行超声心动图检查。
与假手术组相比，起搏组钙蛋白酶I活性显著增加（2.3倍，P < 0.01），抑制剂组降低（1.1倍，P > 0.05）。起搏组和抑制剂组的肌溶解百分比分别为（76.7 ± 5.9）%和（20.8 ± 8.1）%（P < 0.01）。快速起搏诱导的持续性心房颤动中TnT表达降低，而这些作用被钙蛋白酶I抑制剂ALLM抑制。抑制剂组在ALLM治疗3周后左心房面积和容积有增加趋势，但变化不如起搏组显著（P < 0.05）。
ALLM可降低钙蛋白酶I活性，并预防犬心房颤动期间心房心肌细胞结构重塑。本研究提供了一种心房心肌细胞保护能力。
