PDTC对高血压大鼠继发左心室肥厚及心力衰竭的作用  

Effects of PDTC on ventricular hypertrophy and congestive heart failure in hypertensive rats

作　　者：牟鑫煜[1] 张寰[1] 

机构地区：[1]天津市第四中心医院心内科CCU,300140

出　　处：《天津医药》2015年第9期992-995,共4页Tianjin Medical Journal

基　　金：天津市卫生局科技基金资助项目(2013KZ016)

摘　　要：目的评价核因子(NF)-κB抑制剂吡咯烷二硫基甲酸盐(PDTC)对高血压-心室肥厚-充血性心力衰竭大鼠心脏NF-κB活性和血清中各炎症递质的抑制作用。方法 42只雄性Dahl盐敏感大鼠建立高血压-心肌肥厚-心力衰竭动物模型,按随机数字表法分为A组(正常饲料喂养组)、B组(高盐饲料喂养组)、C组(早期NF-κB抑制组)、D组(高血压期NF-κB抑制组)、E组(心肌肥厚期12周NF-κB抑制组)、F组(心肌肥厚期16周NF-κB抑制组)、G组(心力衰竭期NF-κB抑制组),每组6只。各组分别按特定时间段予以8%高盐饲养及PDTC 100 mg/(kg·d)腹腔内注射,观察不同时长的PDCT给药期对血压、左心室舒张末期室间隔厚度(IVSD)、左室舒张末期后壁厚度(LVPWD)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)、心肺质量/体质量比值、NF-κB活性、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、单核细胞趋化蛋白(MCP)-1、C反应蛋白(CRP)的影响。结果早期给予PDTC可抑制NF-κB和促炎症细胞因子水平,大鼠心脏结构改变减轻且心脏功能仅呈轻度降低,给药时间越长,对心脏的保护作用越大,可有效地控制血压,在一定程度上阻断未来可能发生的左室肥厚与左室衰竭。当高血压持续、心肌肥厚形成并伴有心力衰竭的情况下,PDTC用药效果作用有限。结论 PDTC对大鼠高血压、心室肥厚及充血性心力衰竭的发生发展具有预防和治疗作用,早期应用对维持大鼠心脏的正常心功能作用更加明显。Objective To evaluate the inhibitory effects of NF-κB inhibitor pyrrolidine dithiocar-bamate （PDTC） on NF-kappa B activity and the serum inflammatory mediators in hypertensive-ventricular hypertrophy-congestive heart failure rats. Methods The rat model of hypertension-cardiac hypertrophy-heart failure was made from 42 male Dahl salt sensitive rats. Rats were randomly divided into seven groups including group A （normal diet group）, group B （high salt diet group）, group C （NF-κB inhibition in early stage）, group D （NF-κB inhibition in hypertensive stage）, group E （NF-κB inhibition in cardiac hypertrophy stage of week 12） and group G （NF-κB inhibition in heart failure stage）. There were six rats for each group. Rats were administrated 8%high salt diet and injected PDTC 100 mg/（kg·d）intraperitoneally according to the prescribed time. Changes of blood pressure, left ventricular end diastolic interventricular septal thickness （IVSD）, left ventricular end diastolic posterior wall thickness （LVPWD）, left ventricular end diastolic diameter （LVEDD）, systolic left ventricular end diastolic diameter （LVESD）, left ventricular ejection fraction （LVEF）, heart, lung weight/ body weight ratio, NF-kappa B activity, tumor necrosis factor （TNF）-α, interleukin （IL）-6, monocyte chemotactic protein （MCP）-1 and C-reactive protein （CRP） were observed in different treatment time points of PDCT. Results Levels of NF-κB and proinflammatory cytokines were reduced after early administration of PDTC, and the cardiac function was also decreased. The longer the treatment time, the greater the protective effect on heart. PDTC can effectively control blood pressure, and block left ventricular hypertrophy and left ventricular failure in a certain extent. The effects of PDTC were limited after persistent hypertension, and myocardial hypertrophy formation accompanied by heart failure. Conclusion PDTC plays a role in prevention and treatment of hypertension, left ventricular h

关 键 词：高血压 心肌病 肥厚性 心力衰竭 细胞因子类 大鼠 吡咯烷二硫基甲酸盐 

分 类 号：R541.3[医药卫生—心血管疾病]