Ji R R, Zhang Q, Pettersson R F, Hökfelt T
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Regul Pept. 1996 Oct 22;66(3):179-89. doi: 10.1016/S0167-0115(96)00101-2.
Using immunohistochemistry and in situ hybridization the in vivo effects of acidic and basic fibroblast growth factor (aFGF, bFGF), and of nerve growth factor (NGF) on the expression of galanin, neuropeptide Y (NPY) and substance P in axotomized dorsal root ganglia (DRGs) were examined. Self-mutilation (autotomy), a supposed pain-related behavior, was investigated after growth factor treatment. One microgram of aFGF, bFGF or NGF was applied directly to the transected sciatic nerve via a capsule. In normal rats 3.2%, 0% and 17.5% of the neuron profiles in the DRGs contained galanin-, NPY- and substance P-like immunoreactivity (LI), respectively. Sciatic nerve transection induced a distinct increase in galanin- and NPY-LIs, but a downregulation of substance P-LI. Thus three days after axotomy 23.5%, 26.9% and 9.8% of the DRG neuron profiles showed immunoreactivity for galanin-, NPY- and substance P-LI, respectively. In vivo administration of aFGF counteracted the axotomy-induced increase in galanin and NPY, whereas bFGF only suppressed NPY upregulation. NGF reversed in the injury-induced decrease in substance P-LI, but had no significant effect on galanin- and NPY-LIs. These results were confirmed by monitoring the mRNA levels for these neuropeptides. Moreover, aFGF was found to induce autotomy in 60% of the rats 3 days after axotomy. NGF produced autotomy in about 30% of the rats. Taken together, the present results suggest (1) that aFGF, bFGF and NGF differentially regulate neuropeptide expression in vivo; (2) that FGFs can inhibit neuropeptide upregulation of some peptides after nerve injury; and (3) that aFGF and NGF may induce pain-related behavior.
运用免疫组织化学和原位杂交技术，研究了酸性和碱性成纤维细胞生长因子（aFGF、bFGF）以及神经生长因子（NGF）对坐骨神经切断术后背根神经节（DRG）中甘丙肽、神经肽Y（NPY）和P物质表达的体内效应。在生长因子处理后，对自残行为（自切）这一假定的疼痛相关行为进行了研究。将1微克aFGF、bFGF或NGF通过胶囊直接应用于切断的坐骨神经。在正常大鼠中，DRG中分别有3.2%、0%和17.5%的神经元轮廓含有甘丙肽、NPY和P物质样免疫反应性（LI）。坐骨神经切断术导致甘丙肽和NPY-LI明显增加，但P物质-LI下调。因此，在轴突切断术后三天，分别有23.5%、26.9%和9.8%的DRG神经元轮廓显示出对甘丙肽、NPY和P物质-LI的免疫反应性。aFGF的体内给药抵消了轴突切断术诱导的甘丙肽和NPY增加，而bFGF仅抑制了NPY的上调。NGF逆转了损伤诱导的P物质-LI减少，但对甘丙肽和NPY-LI没有显著影响。这些结果通过监测这些神经肽的mRNA水平得到证实。此外，发现aFGF在轴突切断术后三天诱导60%的大鼠出现自切行为。NGF在约30%的大鼠中产生自切行为。综上所述，目前的结果表明：（1）aFGF、bFGF和NGF在体内对神经肽表达有不同的调节作用；（2）FGFs可以抑制神经损伤后某些肽的神经肽上调；（3）aFGF和NGF可能诱导疼痛相关行为。
