核因子-κB在慢性间歇性低氧对大鼠左心功能影响中的作用

Role of NF-κB in cardiac dysfunction due to chronic intermittent hypoxia in rats

摘要:

目的 了解慢性间歇性低氧对大鼠左心功能的影响, 探讨NF-κB在其发生机制中的作用。方法 将24只SD大鼠随机分为3组: 正常对照组（NC）、慢性间歇性低氧组（CIH）, CIH＋PDTC（吡咯烷二硫代氨基甲酸盐,NF-κB抑制剂）组。CIH组每天白天置于间歇性低氧箱（最低氧浓度5%～7%）8 h, 共5周; CIH＋PDTC组每天腹腔注射PDTC 100mg/kg, 饲养环境与CIH组相同; 正常对照组给予相似的处理, 但是维持空气氧浓度不变。测量大鼠体重、血压、心率, 超声心动图评价心功能; 最后提取大鼠心肌组织核蛋白, Western blot法测量NF-κB蛋白水平的表达。结果 第5周时CIH组和CIH＋PDTC组体重低于NC组。CIH组和CIH＋PDTC组血压明显高于NC组[分别为（136.3±6.8）、（134.3±6.7）和（122.3±4.1）mmHg, P＜0.01], CIH组和CIH＋PDTC组两组间差异无统计学意义。CIH组LVEF低于NC组[分别为（73±6）% 和（86±4）%, P＜0.001], CIH＋PDTC组[（84±4）%]较CIH组明显升高（P＜0.001）, 与NC组比较没有明显差异（P=0.117）。各组心率无明显统计学差异。NF-κB蛋白水平的表达CIH组高于NC组和CIH＋PDTC组, NC组与CIH＋PDTC组间没有统计学差异。结论 慢性间歇性低氧大鼠左心功能减低, NF-κB可能参与其作用机制。

Abstract:

Objective To investigate the impact of chronic intermittent hypoxia (CIH) on cardiac function, and explore the role of NF-κB in the mechanisms of cardiac dysfunction due to CIH. Methods Twenty-four adult male Sprague-Dawley rats (body mass about 200g) were randomly divided into three groups: normal control(NC) group, CIH group and CIH＋proline dithiocarbamate(PDTC) group. The rats in CIH group were exposed to intermittent hypoxia (O2 5%～7%), 8 hours daily, totally 5 weeks. The rats in CIH＋PDTC group were raised under the condition similar to CIH group except intraperitoneal injection of PDTC [100mg/(kg?d)]. At the end of the exposure, body mass, blood pressure and heart rate of the animals were measured. Left global function was assessed by echocardiography. Nucleoprotein NF-κB level was detected by Western blot. Results At 5 weeks, the body mass of rats in CIH and CIH＋PDTC groups was lower than that in NC group. Compared to NC group, animals in CIH and CIH＋PDTC groups demonstrated an elevation in blood pressure [ (136.3±6.8) and (134.3±6.7) vs (122.3±4.1) mmHg, P＜0.001]; while the blood pressure was not significantly different between CIH and CIH＋PDTC groups. Left ventricular ejection fraction(LVEF) was lower in CIH group than in NC group [(73.0±5.6) % vs (86.0±4.3) %, P＜0.001], and higher in CIH＋PDTC group than in CIH group [(84.0±4.1) % vs (73.0±5.6) %, P＜0.001]. However, it was not significantly different between NC and CIH＋PDTC groups (P=0.117). There was no significant difference in heart rate among the groups. Compared to NC and CIH＋PDTC groups, the expression of NF-κB increased in CIH group (P＜0.001). However, there was no difference between NC and CIH＋PDTC groups. Conclusion Chronic intermittent hypoxia may impair left ventricular function of rats and NF-κB may be involved in the mechanisms.