Fink T, Di Sebastiano P, Büchler M, Beger H G, Weihe E
Department of Anatomy, University of Mainz, Germany.
Neuroscience. 1994 Nov;63(1):249-66. doi: 10.1016/0306-4522(94)90020-5.
Growth-associated protein-43, an established marker of neuronal plasticity during development and in injury, was used to characterize innervation in the normal human pancreas and changes in chronic alcohol-induced pancreatitis by using light microscopic immunocytochemistry and computer-assisted image analysis. Immunostaining for the pan-neuronal marker protein gene-product 9.5 served as a reference for the characterization of total innervation in both groups. In normal human pancreas, strong protein gene-product 9.5 immunostaining revealed all nerve fibres in nerve trunks, all neuronal cell bodies and the entire parenchymal innervation. In contrast, growth-associated protein-43 immunoreactivity was restricted to a few nerve fibres in interlobular nerve trunks and to fine varicose nerve fibres supplying the parenchyma, blood vessels, pancreatic ducts and intrinsic ganglia. In cell bodies of intrinsic neurons, growth-associated protein-43 immunoreactivity was absent or extremely faint. In chronic pancreatitis, the protein gene-product 9.5 innervation exhibited region-specific changes. In areas with reduced parenchyma, the protein gene-product 9.5 innervation was sparse. In fibrotic regions, which are characteristic for advanced stages of chronic pancreatitis, enlarged nerve trunks showing neuroma-like formations were heavily stained for protein gene-product 9.5. In fibrotic tissue, protein gene-product 9.5-containing nerve fibres were extremely rare. The growth-associated protein-43 innervation in chronic pancreatitis was characterized by a dramatic increase, which was most pronounced in the enlarged nerve trunks. Such nerve trunks were frequently surrounded by infiltrates of immune cells, which in some cases formed follicle-like structures. Digital image analysis of adjacent sections and double fluorescence immunocytochemistry revealed that growth-associated protein-43 immunoreactivity was present in the vast majority of protein gene-product 9.5-immunoreactive nerve fibres. In contrast to the normal pancreas, a major subpopulation of intrinsic neurons immunostained for growth-associated protein-43. The expression of growth-associated protein-43 in the terminal fields of pancreatic nerve suggests that the innervation of the normal human pancreas undergoes continual and toposelective remodelling. The increase in the density of growth-associated protein-43 immunoreactive nerve fibres in enlarged nerve trunks paralleled by augmented expression of growth-associated protein-43 in intrinsic neurons and reduced parenchymal growth-associated protein-43-immunoreactive innervation underline the dramatic plasticity of pancreatic innervation in chronic pancreatitis.(ABSTRACT TRUNCATED AT 400 WORDS)
生长相关蛋白43是发育和损伤过程中已确立的神经元可塑性标志物，本研究通过光学显微镜免疫细胞化学和计算机辅助图像分析，利用该蛋白对正常人体胰腺的神经支配以及慢性酒精性胰腺炎中的变化进行了特征描述。泛神经元标志物蛋白基因产物9.5的免疫染色作为两组中总神经支配特征描述的参考。在正常人体胰腺中，蛋白基因产物9.5的强免疫染色显示了神经干中的所有神经纤维、所有神经元细胞体以及整个实质内的神经支配。相比之下，生长相关蛋白43的免疫反应性仅限于小叶间神经干中的少数神经纤维以及供应实质、血管、胰管和固有神经节的细小曲张神经纤维。在固有神经元的细胞体中，生长相关蛋白43的免疫反应性缺失或极其微弱。在慢性胰腺炎中，蛋白基因产物9.5的神经支配呈现出区域特异性变化。在实质减少的区域，蛋白基因产物9.5的神经支配稀疏。在慢性胰腺炎晚期特征性的纤维化区域，显示神经瘤样形成的增粗神经干被蛋白基因产物9.5重度染色。在纤维化组织中，含蛋白基因产物9.5的神经纤维极其罕见。慢性胰腺炎中生长相关蛋白43的神经支配以显著增加为特征，在增粗的神经干中最为明显。这样的神经干经常被免疫细胞浸润包围，在某些情况下形成滤泡样结构。对相邻切片的数字图像分析和双重荧光免疫细胞化学显示，生长相关蛋白43的免疫反应性存在于绝大多数蛋白基因产物9.5免疫反应性神经纤维中。与正常胰腺不同，大量固有神经元对生长相关蛋白43呈免疫染色。胰腺神经终末区域生长相关蛋白43的表达表明，正常人体胰腺的神经支配经历着持续的和拓扑选择性重塑。增粗神经干中生长相关蛋白43免疫反应性神经纤维密度的增加，与固有神经元中生长相关蛋白43表达的增强以及实质内生长相关蛋白43免疫反应性神经支配的减少相平行，这突显了慢性胰腺炎中胰腺神经支配的显著可塑性。（摘要截于400字）
