Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells
Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells
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DOI：
10.1023/a:1018466608614
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发表时间：
1997-09-01
影响因子：
4
通讯作者：
Burnstock, G
中科院分区：
文献类型：
--
作者：
Ashraf, S;Loizidou, M;Burnstock, G
肝动脉灌注（HAI）化疗作为人类结直肠癌肝转移的治疗是有希望的，但并不完全令人满意。通过操纵正常血管与肿瘤血管的不同控制机制，可以实现HAI期间改善的药物递送。研究了正常肝脏和两种肝转移动物模型（患有同系MC 28肉瘤的Lister Hooded大鼠;患有人HT 29癌的无胸腺（裸）大鼠）中血管的肽能/胺能神经支配，以评估这些模型对未来药理学研究的适用性。应用免疫组化法检测正常肝和转移瘤组织中蛋白基因产物9.5（PGP）、神经肽Y（NPY）、酪氨酸羟化酶（TH）、降钙素基因相关肽（CGRP）、血管活性肠肽（VIP）和P物质（SP）的含量。血管周围的神经支配也通过透射电子显微镜检查。在Lister大鼠正常肝脏，在肝门附近的小叶间血管周围和汇管区内可见含有PGP、NPY、TH、CGRP和SP的血管周围免疫反应阳性神经纤维。PGP密度最高，依次为NPY、TH、CGRP和SP，未见VIP免疫反应阳性神经。肝小叶内未见免疫反应性神经。在无胸腺大鼠肝脏，神经支配的模式是相似的，除了SP免疫反应性更稀疏。在MC 28或HT 29肿瘤中均未观察到血管周围免疫反应性神经。电子显微镜证实了血管周围神经的情况下。在肿瘤血管壁中未观察到平滑肌细胞。这些结果与以前对人肝转移的观察结果相当，并表明动物模型可能适用于HAI化疗血管操作的药理学研究。
Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.