摘要
目的观察慢性充血性心力衰竭(CHF)兔左心室三层心肌间跨室壁缝隙连接蛋白43(Cx43)分布的差异,探讨CHF易发恶性室性心律失常(MVA)的蛋白机制。方法将24只新西兰大白兔随机分成假手术组(Sham组,n=12)和CHF组(n=12)。CHF组通过腹主动脉缩窄建立CHF模型,Sham组开腹未结扎,术后同等条件饲养8周。在体检查超声心动图比较两组兔左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、室间隔厚度(IVS)、左心室后壁厚度(LVPW)和左室射血分数(LVEF);在体血流动力学检查比较两组外周血收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)、左心室最大上升速度和最大下降速度(±dp/dtmax)等参数。将兔处死后制作左心室心肌病理切片,经HE染色后光镜下观察心肌病理改变。分别切取左心室心内膜下心肌(Endo)、中层心肌(Mid)、心外膜下心肌(Epi),采用Western blotting、RT-PCR及免疫组化方法检测三层心肌间Cx43蛋白(Cx43-pro)和mRNA(Cx43-Cq)的表达,计算三层心肌间最大Cx43-pro与最小Cx43-pro之差(ΔCx43-pro)以及最大Cx43-Cq与最小Cx43-Cq之差(ΔCx43-Cq)。结果与Sham组相比,CHF组SBP、DBP、MAP、±dp/dtmax、LVEF明显降低,LVEDD、LVESD明显升高(P<0.05),而IVS、LVPW两组比较差异无统计学意义(P>0.05)。CHF组三层心肌的Cx43蛋白及mRNA表达均低于Sham组(P<0.05);两组中层心肌的Cx43蛋白及mRNA表达均低于心内膜下及心外膜下心肌组织,但CHF组的ΔCx43-pro和ΔCx43-Cq明显高于较Sham组(P<0.05)。结论CHF兔左心室三层心肌的Cx43蛋白发生重构,含量明显减少,跨室壁Cx43表达的异质性增大。
Objective To observe the transmural distributed heterogeneity of the expression of connexin 43(Cx43) in three layers of left ventricle myocardium, and explore the physiological mechanisms of malignant ventricular arrhythmia(MVA) in a rabbit model with chronic congestive heart failure(CHF). Methods Twenty four New Zealand white rabbits were randomly divided into sham operation group(n=12) and CHF group(n=12) which were established with traditional abdominal aorta constriction. After operation, all rabbits were fed under the same conditions for 8 weeks. The left ventricular end diastolic diameter(LVEDD), left ventricular end systolic diameter(LVESD), thickness of the ventricular septum(IVS), thickness of the left ventricular posterior wall(LVPW) and the left ventricular ejection fraction(LVEF) were compared by in vivo echocardiography;the parameters of systolic blood pressure(SBP), diastolic blood pressure(DBP), mean arterial pressure(MAP), and maximum velocity of left ventricle and maximum descending speed(±dp/dtmax) were assessed by haemodynamic measurements between the two groups. The histopathological changes of left ventricular myocardium were observed by optical microscopy. The subendocardial myocardium(Endo), middle myocardium(Mid) and subepicardial myocardium(Epi) of left ventricular were resected, and the expression levels of Cx43 protein(Cx43-pro) and mRNA(Cx43-Cq) in all the three layers were measured by Western blotting, RTPCR and immunohistochemical methods. Results Compared with sham operation group, the SBP, DBP, MAP and ±dp/dtmaxdecreased significantly(P<0.05) in CHF group. The LVEF were obviously decreased, and LVEDD and LVESD were significantly increased(P<0.05) in CHF group when compared with that in sham operation group, while no significant difference existed on IVS and LVPW(P>0.05). The expression levels of Cx43-pro and Cx43-Cq in all the three layers of myocardium decreased in CHF group than in Sham group(P<0.05). The expressions of Cx43-pro and Cx43-Cq in Mid were markedly decreased than i
作者
吴美霞
刘亚军
陆士娟
孙定军
吴淼
张伟
黄康
钟江华
WU Mei-xia;LIU Ya-jun;LU Shi-juan;SUN Ding-jun;WU Miao;ZHANG Wei;HUANG Kang;ZHONG Jiang-hua(Department of Cardiology,Haikou Hospital Affiliated to Xiangya School of Medicine,Central South University,Haikou 570208, China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2018年第11期910-916,共7页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金(81660057)
海南省自然科学基金(2018CXTD349)~~
