Li Wei, Knowlton David, Van Winkle Donna M, Habecker Beth A
Dept. of Physiology and Pharmacology L334, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2229-36. doi: 10.1152/ajpheart.00768.2003. Epub 2004 Jan 15.
Regional changes occur in the sympathetic innervation of the heart after myocardial infarction (MI), including loss of norepinephrine (NE) uptake and depletion of neuronal NE. This apparent denervation is accompanied by increased cardiac NE spillover. One potential explanation for these apparently contradictory findings is that the sympathetic neurons innervating the heart are exposed to environmental stimuli that alter neuronal function. To understand the changes that occur in the innervation of the heart after MI, immunohistochemical, biochemical, and molecular analyses were carried out in the heart and stellate ganglia of control and MI rats. Immunohistochemistry with panneuronal markers revealed extensive denervation in the left ventricle (LV) below the infarct, but sympathetic nerve fibers were retained in the base of the heart. Western blot analysis revealed that tyrosine hydroxylase (TH) expression (normalized to a panneuronal marker) was increased significantly in the base of the heart and in the stellate ganglia but decreased in the LV below the MI. NE transporter (NET) binding sites, normalized to total protein, were unchanged, except in the LV, where [3H]nisoxetine binding was decreased. TH mRNA was increased significantly in the left and right stellate ganglia after MI, while NET mRNA was not. In the base of the heart, increased TH coupled with no change in NET may explain the increase in extracellular NE observed after MI. Coupled with substantial denervation in the LV, these changes likely contribute to the onset of cardiac arrhythmias.
心肌梗死（MI）后，心脏的交感神经支配会发生区域性变化，包括去甲肾上腺素（NE）摄取功能丧失和神经元NE耗竭。这种明显的去神经支配伴随着心脏NE溢出增加。对于这些明显相互矛盾的发现，一种可能的解释是，支配心脏的交感神经元受到改变神经元功能的环境刺激。为了了解MI后心脏神经支配发生的变化，对对照大鼠和MI大鼠的心脏及星状神经节进行了免疫组织化学、生化和分子分析。使用全神经元标记物进行免疫组织化学分析显示，梗死下方的左心室（LV）存在广泛的去神经支配，但心脏基部保留了交感神经纤维。蛋白质印迹分析显示，心脏基部和星状神经节中酪氨酸羟化酶（TH）的表达（以全神经元标记物标准化）显著增加，但MI下方的LV中TH表达降低。以总蛋白标准化的NE转运体（NET）结合位点没有变化，但LV中[3H]尼索西汀结合减少。MI后，左、右星状神经节中TH mRNA显著增加，而NET mRNA没有变化。在心脏基部，TH增加而NET无变化可能解释了MI后观察到的细胞外NE增加。再加上LV中大量的去神经支配，这些变化可能导致心律失常的发生。
