摘要
目的探讨β3-肾上腺素能受体（β3-AR）阻断剂（SR59230A）对异丙肾上腺素（ISO）诱导心力衰竭（心衰）大鼠心功能及左室重构影响的作用机制。方法选择雄性Wistar大鼠85只,采用随机方法分组。8只作为对照组,另77只应用ISO制备心衰模型,共存活20只。再按随机数字表法将存活动物分为ISO组（n=10）及SR59230A组（SR组,n=10）。ISO组给予生理盐水1ml,每日2次腹腔注射;SR组给予SR59230A（85nmol溶于1ml生理盐水）,每日2次腹腔注射;对照组不予处置。治疗6周后SR组与ISO组各死亡1只,对各组存活大鼠进行有创血流动力学、左心室重量/体重（LVW/BW）比值、肺脏重量/体重（PW/BW）比值测定;用逆转录-聚合酶链反应（RT-PCR）及蛋白质免疫印迹法（Western blotting）测定内皮型一氧化氮合酶（eNOS）的mRNA与蛋白表达,用酶联免疫吸附法（ELISA）测定心肌组织环磷酸鸟苷（cGMP）水平。结果与对照组比较,ISO组左室收缩末期压力（LVESP）、左室压力最大上升或下降速率（±dp/dtmax）均显著降低（P均〈0.01）,而心率（HR）、左室舒张末期压力（LVEDP）均显著增高（P均〈0.01）。与ISO组比较,SR组LVESP、±dp/dtmax均明显增高（P〈0.05或P〈0.01）,但与对照组比较差异仍有统计学意义（P〈0.05或P〈0.01）。SR组HR、LVEDP较ISO组均明显降低（P〈0.05和P〈0.01）,其中HR与对照组比较差异无统计学意义（P〉0.05）,而LVEDP仍显著高于对照组（P〈0.01）。与ISO组比较,SR组eNOS的mRNA和蛋白表达水平及心肌组织cGMP水平均显著降低（P均〈0.01）。此外,SR组较ISO组LVW/BW比值及PW/BW比值均明显降低（P均〈0.05）。结论长期给予β3-AR阻断剂SR59230A可以有效阻断心衰动物的β3-AR-NOS-cGMP通路,显著改善心功能,并在一定程度上改善心室重构。
Objective To investigate the effect of β3-adrenoceptor （β3-AR） antagonist （SR59230A） on the cardiac function and left ventricular remodeling in a rat model of heart failure induced by isoprel （ISO）, and to probe into its mechanism. Methods Eight rats were randomly selected to serve as controls from 85 male adult Wistar rats. After a heart failure model was reproduced, twenty remain rats were randomly divided into ISO group （n=10） and SR59230A group （SR group, n=10）. ISO group received intraperitoneal injection of 1 ml saline twice a day; SR group received intraperitoneal injection of 85 nmol SR59230A in 1 ml saline twice a day; control group received no treatment. The parameters determined included echocardiogram, the expression of nitric oxide synthase （eNOS） of left ventricle by the technique of reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting, cyclic guanosine monophosphate （cGMP） level by enzyme linked immunosorbent assay （ELISA）, the ratio of left ventricular weight and body weight （LVW/BW）, and the ratio of lung weight and body weight （PW/BW）. Results Compared with control group, the left ventricular end systolic pressure （LVESP）, the maximun and minimun first derivative of left ventricular pressure （±dp/dtmax） were significantly decreased （all P〈0.01）, while heart rate （HR） and left ventricular end-diastolic pressure （LVEDP） were significantly increased （both P〈0.01） in ISO group. Compared with ISO group, LVESP, ±dp/dtmax were markedly higher （P〈0.05 or P〈0.01） respectively, whereas HR and LVEDP were markedly lower （P〈0.05 and P〈0.01） in SR group, and there was no difference in HR between SR group and control group （P〉0.05）, while LVEDP was higher in RS group than control group （P〈0.01）. The levels of eNOS mRNA, protein and cGMP were significantly lower in SR group compared with ISO group （all P〈0.01）. In addition, when compared with ISO group, LVW/BW ratio and PW/BW ratio in SR group were also decreased （both P〈0.05）. Conclusion β3-AR antagonist SR59230A can block the β3-AR-NOS-cGMP pathway and improve cardiac function in heart failure in rat when if is administered for a long term. SR59230A can also improve left ventricular remodeling in a certain degree.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2007年第11期675-678,共4页
Chinese Critical Care Medicine
基金
黑龙江省卫生厅医学科研课题（2006-041）
黑龙江省教育厅科学技术研究项目（11511228）
黑龙江省研究生刨新科研基金资助项目（200401060）
