CAJ | 학술논문

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。
목적：탐토장효초산지대심기경사후심력쇠갈대서심공능화폐α1、β신상선소수체（AR）각아형표체수평적영향。방법선용웅성Wistar대서90지，분위정상대조조（N조，n＝9）、가수술조（SH조，n＝8），기여73지대서결찰좌관상동맥전강지제작심기경사후심력쇠갈모형，성공44지，분위심력쇠갈모형조（HF조，n＝9）、초산지소제량조（LN조，n＝9）、초산지대제량조（HN조，n＝9）、양성약물대조조（오미사탄지，OL조，n＝9）급초산지대제량연합양성약물조（HN＋OL조，n＝8），관위법급약6주。초성심동도검측용약전후심공능，역전록?취합매련반응（RT-PCR）화면역인적법（Western blot）검측각조폐β1-AR、β2-AR、β3-AR、α1A-AR、α1B-AR급α1D-AR적표체수평。결과용약후，여HF조비교，HN조、OL조급HN＋OL조좌실사혈분수（LVEF）현저승고（P＜0.05）。여SH조상비，HF조β1-AR화β3-AR표체수평명현하강（P＜0.05），α1A-AR、α1B-AR화β2-AR표체수평명현승고（P＜0.05）；여HF조상비，HN조、OL조화HN＋OL조β1-AR、β3-AR표체수평명현승고（P＜0.05），α1A-AR、α1B-AR급β2-AR표체수평명현강저（P＜0.05）。여OL조상비，HN＋OL조각수체표체수평차이경현저（P＜0.05）。각조대서α1D-AR표체수평간차이무통계학의의（P＞0.05）。결론응용장효초산지약물가현저제고심기경사후심력쇠갈대서LVEF，사심력쇠갈대서폐α1、β-AR각아형표체수평반향조절추우정상，대보호폐공능기도료유익적치료작용。
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.