摘要
目的观察西拉普利和缬沙坦对心房颤动（房颤）犬心房肌钙激活蛋白酶（calpains）mR-NA和蛋白表达及心房结构重构的影响。方法27只犬随机分为假手术组、对照组、西拉普利组和缬沙坦组。对照组、西拉普利组和缬沙坦组犬以400次／min心房快速起搏6周，建立房颤犬模型。假手术组犬埋植起搏器后不起搏。测量左心房容积及收缩功能变化，记录房颤诱发及维持情况，检测心房肌calpains mRNA和蛋白表达，观察心房肌病理组织学和超微结构改变。结果西拉普利组和缬沙坦组犬心房肌calpain I mRNA和蛋白表达较假手术组增多（P〈0．05），但较对照组显著减少（P〈0．01）。各组犬心房肌calpain I蛋白表达与肌溶解高度相关（r=0．89，P〈0．01）。各组犬心房肌calpain Ⅱ mRNA和蛋白表达差异无统计学意义。与对照组相比，西拉普利组和缬沙坦组犬心房肌病理组织学和超微结构改变显著减轻，左心房及左心耳容积明显减小，左心房收缩功能显著增强，房颤诱发率和持续时间明显降低。结论房颤犬心房肌calpain I mRNA和蛋白表达显著上调。西拉普利和缬沙坦能明显抑制房颤犬心房肌calpain I表达，防治心房结构重构，减少房颤发生。
Objective The present study was designed to evaluate the effects of cilazapril and valsar-tan on the mRNA and protein expressions of atrial calpain Ⅰ and calpain Ⅱ , and atrial structural remodeling in dogs with atrial fibrillation （AF） induced by chronic, rapid atrial pacing. Methods Twenty-seven dogs were randomly divided into the sham-operated group （ n = 6 ）, control group （ n = 7 ）, cilazapril group （ n = 7 ） and val- sartan group（ n = 7 ）. The dogs in the control group, cilazapril group and valsartan group were subjected to rapid atrial pacing at 400 bpm for 6 weeks, whereas the pacemakers in the sham-operated group were not operational. The dogs in the cilazapril and valsartan groups were given cilazapril（ 1 mg·kg^-1·d^-1 ） or valsartan（30 mg·kg^-1·d^-1） respectively from 1 week before pacing until pacing was stopped. Transthoracic and transoesopha-geal echocardiographic examinations were performed to detect the changes in left atrium volume and contractile function. The inducibility and dtiration of AF were measured in all groups. The mRNA expressions of atrial calpain Ⅰ and calpain Ⅱ were semi-quantified by reverse transcription polymerase chain reaction. The protein levels of calpain Ⅰ and calpain Ⅱ in atrial myocardium were measured by Western-blot method. Patho- histological and ultrastructural changes in atrial tissue were assessed by light and electron microscopy. Results After 6-week pacing, the mRNA and protein expressions of calpain I were up-regulated dramatically in the control group compared to those in the sham-operated group, and the protein expressions of calpain I in all groups correlated closely with the myalysis （r = 0. 89 ,P 〈 0.01 ）. Cilazapril and valsartan could significantly inhibit the mRNA and protein expressions of calpain I. No differences were found in the mRNA and protein expressions of calpain Ⅱ among the groups. Compared with the control group, dramatically smaller left atrium and left atrial appendage volumes and markedly
出处
《中华心律失常学杂志》
2008年第4期292-297,共6页
Chinese Journal of Cardiac Arrhythmias
基金
中国博士后基金（2005038210）,黑龙江省教育厅新世纪创新人才基金（1152-NCET-011）,黑龙江省科技攻关项目（GB07C32401）,哈尔滨市科技攻关项目（2004AA9CS196-8）,黑龙江省博士后基金（LRB04-269）
