Zhou Shengmei, Paz Offir, Cao Ji-Min, Asotra Kamlesh, Chai Ning-Ning, Wang Charles, Chen Lan S, Fishbein Michael C, Sharifi Behrooz, Chen Peng-Sheng
Division of Cardiology, Department of Medicine, University of Southern California, USA.
Heart Rhythm. 2005 Dec;2(12):1347-55. doi: 10.1016/j.hrthm.2005.08.027.
Nerve growth factor (NGF) infusion into the right stellate ganglion (RSG) is antiarrhythmic, while NGF infusion into the left stellate ganglion (LSG) is proarrhythmic in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). This functional asymmetry suggests differential neural remodeling.
To test the hypothesis that NGF infusion into the RSG and the LSG can lead to differential beta-adrenoceptor (beta-AR) expression in dogs with MI and CAVB.
We performed immunostaining to quantify beta(1)-AR and beta(3)-AR immunoreactivity in six dogs with MI and CAVB, nine dogs with MI, CAVB, and NGF infusion to the LSG, six dogs with MI, CAVB, and NGF infusion to the RSG, and six normal dogs. There was significantly increased beta(3)-AR immunoreactivity in dogs with NGF infusion into the LSG and significantly decreased beta(3)-AR immunoreactivity in dogs with NGF infusion into the RSG compared with controls and with the MI and CAVB group. There were no significant differences in beta(1)-AR immunoreactivity among these four groups. To determine protein and mRNA expression of beta-ARs, we created MI and CAVB and infused NGF into the LSG in six additional dogs. The noninfarcted left ventricle free wall was harvested 1 week later. The protein level and receptor density of beta(3)-AR (but not beta(1)- or beta(2)-AR) significantly increased in these six dogs compared with normal controls.
We conclude that NGF infusion into the RSG and the LSG in dogs with MI and CAVB induced differential beta(3)-AR expression in the left ventricular myocardium.
在患有心肌梗死(MI)和完全性房室传导阻滞(CAVB)的犬中,将神经生长因子(NGF)注入右侧星状神经节(RSG)具有抗心律失常作用,而将NGF注入左侧星状神经节(LSG)则具有促心律失常作用。这种功能不对称提示存在差异性神经重塑。
检验以下假设,即在患有MI和CAVB的犬中,向RSG和LSG注入NGF可导致β-肾上腺素能受体(β-AR)表达存在差异。
我们对6只患有MI和CAVB的犬、9只患有MI、CAVB且向LSG注入NGF的犬、6只患有MI、CAVB且向RSG注入NGF的犬以及6只正常犬进行免疫染色,以量化β₁-AR和β₃-AR免疫反应性。与对照组以及MI和CAVB组相比,向LSG注入NGF的犬中β₃-AR免疫反应性显著增加,而向RSG注入NGF的犬中β₃-AR免疫反应性显著降低。这四组之间β₁-AR免疫反应性无显著差异。为了确定β-AR的蛋白和mRNA表达,我们又对另外6只犬造成MI和CAVB,并向LSG注入NGF。1周后采集未梗死的左心室游离壁。与正常对照组相比,这6只犬中β₃-AR(而非β₁-或β₂-AR)的蛋白水平和受体密度显著增加。
我们得出结论,在患有MI和CAVB的犬中,向RSG和LSG注入NGF可诱导左心室心肌中β₃-AR表达存在差异。