Nerve growth factor and its high-affinity receptor in chronic pancreatitis
Nerve growth factor and its high-affinity receptor in chronic pancreatitis
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DOI：
10.1097/00000658-199911000-00002
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发表时间：
1999-11-01
影响因子：
9
通讯作者：
Büchler, MW
中科院分区：
文献类型：
--
作者：
Friess, H;Zhu, ZW;Büchler, MW
目的探讨慢性胰腺炎（CP）神经生长与疼痛产生的机制。背景资料慢性胰腺炎是一种疼痛性疾病，伴有特征性神经改变，包括神经数量和直径增加。影响神经生长的机制尚不清楚。神经生长因子（NGF）及其高亲和力的酪氨酸激酶受体A （TrkA）参与中枢神经和周围神经的发育和存活生长。方法采用Northern blot、原位杂交、免疫组化染色等方法检测24例CP患者胰腺中神经生长因子和TrkA水平，并与临床指标进行相关性分析。结果Northern blot结果显示，CP组中NGF和TrkA mRNA表达分别升高42%（13.1倍）和54%（5.5倍）（p < 0.01）。原位杂交显示，在CP中，化生的导管细胞、变性的腺泡细胞和去分化为管状结构的腺泡细胞中NGF mRNA表达增强。TrkA mRNA在神经会膜中强烈存在。此外，CP样本胰腺内神经节细胞中也存在增强的NGF和TrkA mRNA信号。免疫组织化学证实了原位杂交的结果。结果显示，NGF mRNA水平与胰腺纤维化（r = 0.64）、腺泡细胞损伤（r = 0.74）、TrkA mRNA水平与疼痛程度（r = 0.84）呈正相关（p < 0.05）。结论CP中存在NGF/TrkA通路的激活，可能影响CP的神经形态学改变和疼痛综合征。
ObjectiveTo study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP).Summary Background DataChronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves.MethodsNerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters.ResultsBy Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p < 0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p < 0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84).ConclusionActivation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.