长效硝酸酯对心力衰竭大鼠肺α1、β肾上腺素受体各亚型表达水平的影响

Effect of long-acting nitrate on expression of α1-andβ-adrenoceptor subtypes inlung ofrats with heart failure

目的：探讨长效硝酸酯对心肌梗死后心力衰竭大鼠心功能和肺α1、β肾上腺素受体（AR）各亚型表达水平的影响。方法选用雄性Wistar大鼠90只，分为正常对照组（N组，n＝9）、假手术组（SH组，n＝8），其余73只大鼠结扎左冠状动脉前降支制作心肌梗死后心力衰竭模型，成功44只，分为心力衰竭模型组（HF组，n＝9）、硝酸酯小剂量组（LN组，n＝9）、硝酸酯大剂量组（HN组，n＝9）、阳性药物对照组（奥美沙坦酯，OL组，n＝9）及硝酸酯大剂量联合阳性药物组（HN＋OL组，n＝8），灌胃法给药6周。超声心动图检测用药前后心功能，逆转录？聚合酶链反应（RT-PCR）和免疫印迹法（Western blot）检测各组肺β1-AR、β2-AR、β3-AR、α1A-AR、α1B-AR及α1D-AR的表达水平。结果用药后，与HF组比较，HN组、OL组及HN＋OL组左室射血分数（LVEF）显著升高（P＜0.05）。与SH组相比，HF组β1-AR和β3-AR表达水平明显下降（P＜0.05），α1A-AR、α1B-AR和β2-AR表达水平明显升高（P＜0.05）；与HF组相比，HN组、OL组和HN＋OL组β1-AR、β3-AR表达水平明显升高（P＜0.05），α1A-AR、α1B-AR及β2-AR表达水平明显降低（P＜0.05）。与OL组相比，HN＋OL组各受体表达水平差异更显著（P＜0.05）。各组大鼠α1D-AR表达水平间差异无统计学意义（P＞0.05）。结论应用长效硝酸酯药物可显著提高心肌梗死后心力衰竭大鼠LVEF，使心力衰竭大鼠肺α1、β-AR各亚型表达水平反向调节趋于正常，对保护肺功能起到了有益的治疗作用。

ObjectiveTo investigate the effect of long-acting nitrate on theleft ventricular function and the expression ofα1-andβ-adrenergic receptors subtypesin the lungtissue of rats with myocardial infarction-induced chronic heart failure （CHF）.MethodsNinety inbred male Wistar rats were divided into normal control group （Ngroup,n=9）, sham-operation group （SHgroup,n=8） and heart failure（HF）model group （n=73）. The HF model wassuccessfullyinduced by ligating left anterior descending （LAD） artery in 44 rats.In 4 weeks after operation,theratsfromthe model group were divided into 5 groups, HF group （HFgroup,n=9）, low-dose nitrate group（LNgroup,n=9）, high-dose nitrate group （HNgroup,n=9）, positive medicine （olmesartan） control group （OLgroup,n=9） and high dose nitrate combined with positive medicine group （HN＋OLgroup,n=8）. The medication was given by gastric gavage for 6 weeks.Cardiac function was examined by echocardiography before and after the treatment,and theexpressionof β1-AR, β2-AR, β3-AR, α1A-AR, α1B-AR, and α1D-ARat mRNA and proteinlevelsin the lung parenchyma was determined byreverse transcription-polymerase chain reaction（RT-PCR） andWestern blotting.Results After the treatment, left ventricular ejection fraction（LVEF）wasmarkedlyhigher inHN, OL and HN＋OLgroupsthanin HFgroup （P〈0.05）. Compared withSHgroup, the expression of α1A-AR, α1B-AR, and β2-AR was significantly up-regulated （P〈0.05）, andthat of β1-AR andβ3-AR was down-regulated in HFgroup（P〈0.05）. Compared with HFgroup, the expression of α1A-AR, α1B-AR, and β2-AR was significantly down-regulated, and the expression of β1-AR and β3-AR was significantly up-regulated in HN, OL, and HN＋OLgroups（P〈0.05）. Furthermore,therewas significant difference in the expression of above subtypes between theOLgroupand HN＋OLgroup（P〈0.05）. Noobvious difference was seen in theexpression level ofα1D-AR among all groups.ConclusionLong-acting nitratetherapyremarkably improvesLVEF in CHF rats induced bymyocardial infarction,reverses the lung expressionlevelsof α1- andβ-AR subtypes to normal, andexerts abeneficial effect on theprotection of lungfunction.