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糖尿病大鼠胰岛移植的去甲肾上腺素能和胆碱能神经再支配

Noradrenergic and cholinergic reinnervation of islet grafts in diabetic rats.

作者信息

Houwing H, Van Asperen R M, Van der Zee E A, Van Suylichem P T, Oestreicher A B, Steffens A B, Strubbe J H

机构信息

Department of Animal Physiology, University of Groningen, Haren, The Netherlands.

出版信息

Cell Transplant. 1996 Jan-Feb;5(1):21-30. doi: 10.1177/096368979600500106.

DOI:10.1177/096368979600500106
PMID:8665073
Abstract

Grafted islets become denervated due to the islet transplantation procedure. The aim of the present study was 1) to examine whether islet grafts in the liver, the spleen, and under the kidney capsule in rats become reinnervated following the transplantation and experimental procedures used in our laboratory, 2) whether there is any difference in reinnervation at these different sites, and 3) how these results relate to previous physiological experiments. Isogeneic isolated islets were transplanted into diabetic Albino Oxford rats, resulting in normoglycaemia. After at least 5 wk, graft-receiving organs were removed and several antibodies were employed to detect insulin, neuron-specific proteins, and cholinergic and noradrenergic nerve fibers. Islets in all three receiving organs contained viable insulin-positive B-cells. Neuron-specific enolase (NSE) as well as the growth-associated protein B-50 was observed at all sites. The cholinergic marker choline acetyltransferase (ChAT) was localized in islets grafts at all sites, but with the lowest density in the spleen. Staining for the noradrenergic markers tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) was observed in islet grafts at all sites with the lowest density in grafts under the kidney capsule. All these neurochemical substances were most frequently observed in fibers associated with blood vessels, which may be the route along which nerves grow into the graft. It can be concluded that 1) islet grafts in the liver, in the spleen and under the kidney capsule become reinnervated; 2) the innervation pattern of the islet grafts differs only slightly from that in the control pancreatic islets; and 3) in combination with our previously physiological data, we can conclude that these nerve fibers are, at least partly, functionally active.

摘要

由于胰岛移植手术,移植的胰岛会失去神经支配。本研究的目的是:1)研究在我们实验室所采用的移植和实验程序后,大鼠肝脏、脾脏和肾包膜下的胰岛移植是否会重新获得神经支配;2)这些不同部位的重新神经支配是否存在差异;3)这些结果与先前的生理学实验有何关联。将同基因分离的胰岛移植到糖尿病白化牛津大鼠体内,使其血糖恢复正常。至少5周后,取出接受移植的器官,使用几种抗体检测胰岛素、神经元特异性蛋白以及胆碱能和去甲肾上腺素能神经纤维。所有三个接受移植器官中的胰岛均含有存活的胰岛素阳性B细胞。在所有部位均观察到神经元特异性烯醇化酶(NSE)以及生长相关蛋白B-50。胆碱能标志物胆碱乙酰转移酶(ChAT)定位于所有部位的胰岛移植中,但在脾脏中的密度最低。在所有部位的胰岛移植中均观察到去甲肾上腺素能标志物酪氨酸羟化酶(TH)和多巴胺-β-羟化酶(DBH)的染色,肾包膜下移植中的密度最低。所有这些神经化学物质最常出现在与血管相关的纤维中,这可能是神经长入移植组织的途径。可以得出以下结论:1)肝脏、脾脏和肾包膜下的胰岛移植会重新获得神经支配;2)胰岛移植的神经支配模式与对照胰腺胰岛的神经支配模式仅略有不同;3)结合我们先前的生理学数据,我们可以得出结论,这些神经纤维至少部分具有功能活性。

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