程序性细胞死亡因子4与猪冠状动脉微栓塞致心功能损伤的关系及机制研究  

Relationship Between Coronary Micro Embolism Incurred Myocardial Dysfunction and Dynamic Changes of PDCD4 Expression in Experimental Pigs

作　　者：苏强[1] 李浪[1] 周游[1] 王江友[1] 

机构地区：[1]广西医科大学第一附属医院心血管内科,广西壮族自治区南宁市530021

出　　处：《中国循环杂志》2015年第2期176-181,共6页Chinese Circulation Journal

基　　金：国家自然科学基金资助项目(81260042);2014年广西研究生教育创新计划项目(YCBZ2014023)

摘　　要：目的:探讨巴马系小型猪冠状动脉(冠脉)微栓塞(CME)致心功能损伤与程序性细胞死亡因子4(PDCD4)表达的动态变化及关系。方法:60头巴马系小型猪经微导管左前降支注入微栓塞球构建冠脉微栓塞组;注射生理盐水构建假手术组,每组小型猪均为30只。每组小型猪随机分为0 h、3 h、6 h、9 h、12 h、24 h六个不同时间点观察(每个时间点小型猪均为5头)。应用心脏超声心动图检测心功能指标;组织病理切片苏木素-伊红(HE)染色和苏木素碱性复红苦味酸(HBFP)染色进行梗死区域测量;荧光定量多聚酶链反应(PCR)检测心肌组织PDCD4与肿瘤坏死因子-α(TNF-α)mR NA表达;蛋白免疫印迹法(Western blot)检测心肌组织PDCD4与TNF-α蛋白表达。结果:超声心动图参数显示,冠脉微栓塞组除0 h、24 h外其余时间点左心室射血分数(LVEF)均较假手术组明显降低(P<0.05),伴随着LVEF显著下降,心脏超声心动图表现为左心室短轴缩短率(LVFS)和心排血量(CO)下降及左心室舒张末期内径(LVEDd)增加。病理学显示,冠脉微栓塞组3 h、6 h、9 h、12 h、24 h五个时间点均可见微梗死灶,但各时间点之间的微梗死面积比较差异无统计学意义(P>0.05)。荧光定量PCR结果显示,冠脉微栓塞组心肌组织PDCD4与TNF-αmR NA表达都是在3 h开始升高,9 h达高峰,12 h和24 h下降(P<0.05);与假手术组比较,冠脉微栓塞组除0 h外其他时间点心肌组织PDCD4与TNF-αmR NA的表达量均显著增加(均P<0.05)。蛋白免疫印迹结果显示,冠脉微栓塞组心肌组织PDCD4与TNF-α的蛋白表达都是在3 h开始升高,9 h达高峰,12 h和24 h下降(P<0.05);与假手术组比较,冠脉微栓塞组除0 h外其他时间点心肌组织PDCD4与TNF-α蛋白表达水平均显著增加(P均<0.05),差异均有统计学意义。结论:PDCD4参与了冠脉微栓塞致心功能的损伤,并呈现出明显的时间变化规律,可能是通过调控心肌TNF-α的表达实现。Objective： To explore the relationship between coronary micro embolism （CME） incurred myocardial dysfunction and dynamic changes of a programmed cell death 4 （PDCD4） expression in experimental pigs. Methods： A total of 60 Bema miniature pigs were randomly divided into 2 groups： CME group, the animal model was established by injecting polyethylene microspheres into pigs’ left anterior descending artery （LAD） and Sham group, the animals received normal saline injection in LAD. n=30 in each group. Each group was further divided into 5 time points as 0h, 3h, 6h, 9h, 12h and 24h to observe the relevant indexes, n=5 in each time point. The myocardial function was detected by echocardiography, the area of infarction was examined by HIM and HBFP staining, the expressions of mRNA and protein of myocardial PDCD4 and TNF-α were measured by RT-PCR and Western blot analysis at different time points in each group. Results： ① Compared with Sham group, CME group presented decreased LVEF at each time point except for 0h, P〈0.05, and with LVEF decreasing, the FS and CO reduced, while LVEDD increased accordingly. ② In CME group, the micro infraction could be found at 3h, 6h, 9h, 12h and 24h time points, and the areas of infarction were similar among different time points, P〉0.05. ③In CME group, the mRNA expression of PDCD4 and TNF-αincreased at 3h time point, reached the maximum at 9h and decreased at 12h and 24h time points, P〈0.05. Compared with Sham group, CME group had increased mRNA expression of PDCD4 and TNF-α at each point except for 0h, all P〈0.05. ④In CME group, the protein expression of PDCD4 and TNF-α increased at 3h time point, reached the maximum at 9h and decreased at 12h and 24h time points, P〈0.05. Compared with Sham group, CME group had increased protein expression of PDCD4 and TNF-αat each point except for 0h, all P〈0.05. Conclusion： PDCD4 was involved in CME incurred myocardial dysfunction as time changing in experimental pigs, and this might be carried out

关 键 词：冠状动脉微栓塞 血管内介入 心功能 程序性细胞死亡因子4 

分 类 号：R735.9[医药卫生—肿瘤]