Arthritis Research UK Pain Centre, University of Nottingham, City Hospital, Nottingham, UK.
Br J Pharmacol. 2012 Jun;166(4):1261-71. doi: 10.1111/j.1476-5381.2012.01848.x.
We have tested the hypothesis that calcitonin gene-related peptide (CGRP) is a mediator of capsaicin-induced angiogenesis in vivo.
In a series of experiments, the knee joints of rats were injected with CGRP, capsaicin or vehicle control. Groups of animals (n=6) were treated with the CGRP receptor antagonist BIBN4096BS and/or the NK₁ receptor antagonist SR140333. Endothelium, proliferating endothelial cell nuclei and macrophages were identified 24 h later in the synovium by immunohistochemistry and quantified by image analysis. mRNA for the receptors for CGRP and adrenomedullin were sought in normal and inflamed rat and human synovia using RT-PCR.
Intra-articular CGRP injection increased the endothelial cell proliferation index, whereas macrophage infiltration and knee joint diameters were similar to saline-injected controls. CGRP-induced endothelial cell proliferation was dose-dependently inhibited by BIBN4096BS. mRNA for adrenomedullin and the CGRP receptor subunits were detected in normal and inflamed human and rat synovia. In capsaicin-induced synovitis, the increased endothelial cell proliferation index was partially blocked by administration of NK₁ or CGRP antagonists individually and was reduced to the level of saline controls by coadministration of both receptor antagonists.
These data support the hypothesis that CGRP stimulates angiogenesis in vivo directly by activating CGRP receptors. Capsaicin-induced endothelial cell proliferation was completely blocked by coadministration of CGRP and NK₁ receptor antagonists, indicating that both CGRP and substance P may contribute to angiogenesis in this model of synovitis.
我们已经验证了降钙素基因相关肽（CGRP）是体内辣椒素诱导血管生成的介质这一假说。
在一系列实验中，向大鼠膝关节内注射 CGRP、辣椒素或载体对照。用 CGRP 受体拮抗剂 BIBN4096BS 和/或 NK₁ 受体拮抗剂 SR140333 处理动物组（n=6）。24 小时后，通过免疫组织化学法鉴定滑膜中的内皮细胞、增殖的内皮细胞核和巨噬细胞，并通过图像分析进行定量。使用 RT-PCR 在正常和炎症大鼠和人滑膜中寻找 CGRP 和肾上腺髓质素的受体的 mRNA。
关节内注射 CGRP 增加了内皮细胞增殖指数，而巨噬细胞浸润和膝关节直径与盐水对照相似。BIBN4096BS 可剂量依赖性抑制 CGRP 诱导的内皮细胞增殖。在正常和炎症的人及大鼠滑膜中均检测到肾上腺髓质素和 CGRP 受体亚基的 mRNA。在辣椒素诱导的滑膜炎中，单独使用 NK₁ 或 CGRP 拮抗剂可部分阻断内皮细胞增殖指数的增加，而同时使用两种受体拮抗剂可将其降低至盐水对照水平。
这些数据支持 CGRP 通过激活 CGRP 受体直接刺激体内血管生成的假说。同时给予 CGRP 和 NK₁ 受体拮抗剂可完全阻断辣椒素诱导的内皮细胞增殖，表明 CGRP 和 P 物质可能都有助于该滑膜炎模型中的血管生成。
