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

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%)8h,共5周;CIH+PDTC组每天腹腔注射PDTC100mg/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=0.1 17)。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。

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（O_2 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-kB 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,P0.001];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）%,P0.001],and higher in CIH ＋ PDTC group than in CIH group[（84.0±4.1）%vs （73.0±5.6）%,P0.001].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-kB increased in CIH group（P0.001）.However,there was no difference between NC and CIH ＋ PDTC groups.Conclusion Chronic intermittent hypoxia may impair left ventricular function of rats and NF-kB may be involved in the mechanisms.