BRL-37344对心力衰竭大鼠β肾上腺素受体表达水平的影响(英文)

目的　探讨 β3 肾上腺素受体 (β3 AR)及其激动剂BRL 37344 (BRL)在心力衰竭中的作用。方法大鼠分为对照组、异丙肾上腺素 (Iso)组和Iso +BRL组。Iso组和Iso +BRL组大鼠间隔 2 4h ,scIso 340mg·kg- 12次制作心力衰竭模型。 8周后 ,Iso +BRL组大鼠从尾静脉给予BRL 0 .4nmol·kg- 1·min- 1,10min ,每周 2次 ,给药 2或 6周。分别于给Iso后 10或 14周测定死亡率、血流动力学、左室重 /体重、心肌组织 β1 ,β2 和 β3 ARmRNA水平。结果　 14周时对照组、Iso组和Iso +BRL组分别死亡 0 / 2 0 ,3/ 18和 5 / 2 2 (P >0 .0 5 )。Iso使左室收缩末压、±dp/dtmax明显降低 ,左室等容舒张时间常数、左室舒张末压明显增高 ,左室重 /体重明显增加 ;与Iso组比 ,Iso +BRL组的心脏舒缩功能进一步下降 ,左室重 /体重进一步增加。Iso组 β1 ARmRNA水平降低 ,β3 ARmRNA水平升高 ,与Iso组比较 ,Iso +BRL组 β1 ARmRNA水平更低 ,β3 ARmRNA水平更高。β2 ARmRNA 3组均有下降趋势 ,但无统计学差异。结论衰竭心脏β1 AR水平下降及 β3 AR水平增高可导致心功能降低。β3 ARmRNA水平在衰竭心脏比非衰竭心脏明显增高 ,应用 β3 AR激动剂可明显加重心力衰竭。

Effects of BRL-37344 on expression of β-adrenoreceptors mRNA of rats with heart failure

AIM To investigate the influence of β3-adrenoreceptor(β3-AR) and the effect of β3-AR agonist on the failing hearts. METHODS Rats were randomly divided into control group, isoprenaline(Iso) group and Iso+BRL group. Iso group and Iso+BRL group received two sc injections of Iso (340 mg·kg-1) with a 24 h interval to induce heart failure. After 8 weeks, Iso+BRL group was given BRL-37344 0.4 nmol·kg-1·min-1 via tail-vein for 10 min, twice a week for 2 or 6 weeks. Mortality, hemodynamics, ratio of left ventricle weight and body weigh (LVW/BW) and levels of β1-, β2- and β3-AR mRNA were measured at the tenth and the fourteenth week after injection of Iso. RESULTS There was no significant difference in the mortality among the three groups(P>0.05). Left ventricular end systolic pressure (LVESP),±dp/dtmax decreased, and left ventricular end diastolic pressure (LVEDP), LVW/BW increased dramatically in Iso group. When compared with Iso hearts, Iso+BRL group had more deteriorated cardiac functions and higher LVW/BW. The level of β1-AR mRNA was low and the level of β3-AR mRNA was high in Iso group. When compared with Iso hearts, Iso+BRL group had lower level of β1-AR mRNA and higher level of β3-AR mRNA. The level of β2-AR mRNA had no significant difference among three groups. CONCLUSION In failing hearts, reduction in β1-AR mRNA and increase in β3-AR mRNA might contribute to cardiac dysfunctions; the level of β3-AR mRNA is higher than that in control heart; β3-AR agonist aggravates cardiac dysfunctions.