硫辛酸对快速起搏兔心房诱发的心房肌电与结构重构的抑制作用

Inhibitory effects of lipoic acid on atrial electrical and structural remodeling induced by rapid atrial pacing in rabbits

目的:探讨硫辛酸对快速起搏兔心房诱发的急性心房肌电重构以及结构重构的抑制作用及其可能机制。方法:将45只健康新西兰大耳白兔随机分为3组:假手术组(n=10)、起搏组(RAP组,n=10)、起搏+硫辛酸注射组(LA组,n=10)。起搏频率为600次·min^(-1),在起搏0、4、8、12 h分别进行程序刺激,测定心房有效不应期(AERP),并计算AERP频率适应性。刺激结束后,取左心房组织,通过HE染色和Masson染色观察心房组织结构重构情况;通过检测丙二醛(MDA)、活性氧自由基(ROS)水平以及超氧化物歧化酶(SOD)活性观察各组心房肌氧化应激水平。结果:假手术组在不同基础刺激周长(即S1S1周长)作用下,各时间点AERP无显著性改变(P>0.05);与假手术或LA组比较,RAP组AERP逐渐缩短(P<0.05);RAP组起搏开始后8、12 h与起搏前(0 h)比较,AERP_(200~150)频率适应性不良(P<0.05);LA组各时段频率适应性无明显变化(P>0.05)。心房组织HE染色:假手术组心房肌纤维排列整齐、有序;RAP组心房肌纤维排列紊乱,部分区域肌纤维溶解、断裂;LA组心房肌的病理学改变轻于RAP组。心房组织Masson染色:假手术组心房肌纤维呈红色,仅可见少量蓝色的胶原纤维;RAP组心房肌间质中胶原纤维显著增多,分布紊乱;LA组心房肌间质中的胶原纤维含量较RAP组明显减少。氧化应激指标:与假手术相比,RAP组心房组织中丙二醛、ROS含量明显增加(P<0.05),SOD活性下降(P<0.05);与RAP组相比,LA组心房中丙二醛、ROS含量明显减少,SOD活性升高(P<0.05)。结论:在兔心房快速起搏模型中,LA干预能够有效抑制心房肌电重构和结构重构。

Objective: To study the inhibitory effects of lipoic acid on rapid atrial pacing( RAP) induced atrial electrical remodeling and structural remodeling and its possible mechanism in rabbits. Methods: Forty-five New Zealand white rabbits were randomly divided into 3 groups: Sham operated group( sham group,n = 10),RAP group( n = 10),pacing + lipoic acid group( LA group,n = 10). Pacemaker frequency was 600 times per min. Programmed electrical stimulation( PES) was performed in pacing 0,4,8 and 12 h,Atrial effective refractory period( AERP) was monitored,and the AERP frequency adaptability was calculated. The left atrial tissue was taken in the end of stimulus,the levels of the pathological atrial structural remodeling was observed by HE stainingand and the levels of oxidative stress in the atrium of each group was observed by measuring the levels of malondialdehyde( MDA),manganese superoxide dismutase( SOD) and reactive oxygen species( ROS). Results: The AERP at each time point in sham group did not change significantly at different base perimeter stimulation( P > 0. 05); compared with the sham group or RAP group,AERP in RAP group was gradually reduced( P < 0. 05); the rate adaptation of AERP were remarkably shortened in RAP group in pacing 8,12 h compared with 0 h( P < 0. 055). The rate adaptation of AERP did not change significantly in LA group( P > 0. 05). Atrial HE staining showed that atrial muscle fibers arranged in neat and orderly in the sham group,atrial muscle fibers were disordered and some were dissociated and ruptured in the RAP group. Atrial pathological changes of the LA group was lighter than the RAP group. Masson staining showed that red atrial fibers predominated,and only a small amount of blue collagen fibers were founed in the sham group,the content of collagen fibers in the interstitium of atrium was significantly increased and the distribution was disorder in the RAP group; the content of collagen fibers in the interstitium of atrium was improved in the LA group compared with the in RAP group. In the RAP group,the levels of atrium MDA and ROS were significantly increased and the SOD activity was significantly decreased compared with sham group( all P < 0. 05); In the LA group the levels of atrium MDA and ROS were decreased significantly,SOD activity was increased compared with the RAP( all P < 0. 05). Conclusion: LA intervention can inhibit atrial electrical remodeling and structural remodeling in rabbits rapid atrial pacing model.