老龄化家兔左心房重构对房性心律失常的影响

发布时间：2018-06-23 00:57

本文选题：老龄化左心房 + 心肌重构　；参考：《中国病理生理杂志》2017年02期

【摘要】：目的:探讨老龄化左心房(LA)电和结构重构对房性心律失常的影响及机制。方法:选用健康雄性新西兰大耳白兔,分为青龄LA组[兔龄(8±2)月]和老龄LA组[兔龄(25±2)月]。记录在体左心房肌单相动作电位(MAP)和短阵快速刺激方法观察2组动作电位的静息膜电位(RMP)、幅度(APA)、最大上升速率(dv/dt_(max)、平台期电位、复极化到30%、50%和90%时程(APD_(30)、APD_(50)和APD_(90))以及心律失常诱发率和持续时间;全细胞膜片钳技术记录各组L型钙电流(I_(Ca,L);Masson染色观察各组左心房组织间质胶原纤维及其蛋白含量,透射扫描电镜观察左心房细胞内超微结构;Western blot技术测定各组左心房组织Cav1.2蛋白的表达水平。结果:与青龄LA组比较老龄LA组心房肌动作电位的dv/dt_(max)和平台期电位显者降低,APD_(30)和APD_(50)明显缩短,APD_(90)显者延长(P0.01);其房性心律失常的诱发率明显增高,持续时间显著延长(P0.01)。在电压钳制方式下,与青龄LA组比较,老龄LA组左心房肌细胞I_(Ca,L)密度在各钳制电压下均明显减小,其电流-电压曲线显著上抬;当钳制电位为+20 mV时老龄LA组心肌细胞I_(Ca,L)密度由青龄LA组的(11.72±1.39)pA/pF减小为(6.08±0.98)pA/pF(P0.01)。与青龄LA组比较,老龄LA组心肌组织中胶原纤维明显增多,胶原蛋白含量显著增加(P0.01),心房肌组织排列不规则。老龄LA组心房肌细胞超微结构异常改变,心房肌细胞核固缩,线粒体排列杂乱,肿胀或出现空泡,肌小节损伤严重。老龄LA组织中的Cav1.2蛋白表达水平明显小于青龄LA(P0.01),其表达量与老龄LA组I_(Ca,L)密度减小呈显著正相关(r=0.83,P0.01)。结论:老龄LA发生了明显的病理生理特征性改变而增加了老龄化房颤发生的易损性和易感性,其机制与老龄化LA的I_(Ca,L)减小、超微结构改变和Cav1.2蛋白表达水平下降密切相关。
[Abstract]:Aim: to investigate the effect and mechanism of left atrial (LA) electrical and structural remodeling on atrial arrhythmias. Methods: healthy male New Zealand white rabbits were divided into two groups: young LA group (8 卤2 months old) and aged LA group (25 卤2 months old). Left atrial monophasic action potential (map) and short array rapid stimulation were recorded to observe the resting membrane potential (RMP), amplitude (APA), maximum rise rate (DVD / DT _ (max), plateau potential) of action potential in both groups. 50% and 90% of the time course (APD _ (30) and APD _ (90) and the rate and duration of arrhythmias were recorded by whole-cell patch clamp technique, and the contents of collagen fibers and their proteins in the interstitial tissue of left atrium were observed by Masson staining. The expression of Cav1.2 protein in left atrium tissue was measured by Western blot technique. Results: compared with the young LA group, in the aged LA group, the ADV / DT _ (max) and the plateau potential of the atrial muscle action potential decreased significantly (P0.01), and the atrial arrhythmia induction rate increased significantly (P0.01), and the duration of the atrial arrhythmia was significantly prolonged (P0.01) in the aged LA group, which decreased the APD_ (30) and APD50 (P _ (0.01), significantly shortened the APD90 (P _ (0.01), and significantly increased the atrial arrhythmia (P _ (0.01). Compared with the young LA group, the ICaL density of left atrial myocytes in the aged LA group decreased significantly under each clamp voltage, and the current-voltage curve increased significantly under the voltage clamping mode. When the clamp potential was 20 MV, the density of I _ (CaAL) in aged LA group decreased from (11.72 卤1.39) Pa / PF to (6.08 卤0.98) Pa / PF (P0.01). Compared with the young LA group, the collagen fibers in the myocardium and the collagen content in the aged LA group were significantly increased (P0.01), and the arrangement of atrial muscle tissue was irregular. In the aged LA group, the ultrastructure of atrial myocytes was abnormal, the nucleus of atrial muscle was constricted, the mitochondria arranged in disorder, swelling or vacuole appeared, and the injury of muscle section was serious. The expression level of Cav1.2 protein in aged LA was significantly lower than that in young LA (P0.01), and there was a significant positive correlation between the expression of Cav1.2 protein and the decrease of ICaL density in aged LA group (r = 0.83, P 0.01). Conclusion: aging LA has obvious pathophysiological changes and increases vulnerability and susceptibility to aging atrial fibrillation. Its mechanism is closely related to the decrease of I _ (CaFL), ultrastructural changes and the decrease of Cav1.2 protein expression level in aging LA.
【作者单位】：武汉大学人民医院心内科武汉大学心血管病研究所;
【基金】：湖北省自然科学基金资助项目(No.2011CDB504) 湖北省卫计委科研基金资助项目(No.JX6B67;No.WJ2015MB088)
【分类号】：R541.75

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