清热活血解毒法对银屑病神经内分泌免疫网络节点—神经生长因子(NGF)及其受体的调控研究

Psoriasis is a chronic relapsing skin disease, the pathogenesis of it is still an enigma which immunity and environmental factors play crual roles in it. But now days, its physical propertise got more and more attention. As an crossing point of neuroendocrine-immune network, NGF shows a high expression in psoriatical lesions, it can stimulate the proliferation of T cell and karotinocyte, and it can intervene some signal pathways, so we have reasons to believe that NGF and NGFR play a key role in the pathogenesis of Psoriasis..Lots of clinical trails show that the treatmenr of TCM is effective, but the mechanism of it need to be investigeted. In previous studys, we found that the drug serum of Qingre Huoxue Decoction and some monomers can inhibit the proliferation of a variety of psoriasis associated cells in vitro, and affect the expression level of cAMP, CaM,NF-kB in karatinocytes. What is more, the above factors participate the signal transduction pathways of psoriasis, such as Ca2+ -CaMK, NF-kB signal pathways. Therefore, we believe that the mechanism of TCM in treating psoriasis is complex..Even more, the targets of NGF influenced and Qingre huoxue Decoction treated, make highly consistent. Therafore, we suggest that NGF and NGFR may be the key target of TCM in treating psoriasis which maybe the upstream of the intevene.

银屑病是一种多基因遗传背景下,受环多种境因素影响的免疫性皮肤疾病，其身心属性日益受到关注。作为神经内分泌免疫网络节点的神经生长因子在银屑病皮损处高表达，可刺激T细胞及角质形成细胞的增殖，参与多条信号传导通路，在银屑病发病过程中起关键作用。临床研究显示中医药治疗银屑病是具有一定优势，然而其治疗的作用机制却有待于深入研究。前期研究中，我们发现清热活血解毒方药的含药血清及部分中药单体可抑制多种银屑病相关细胞的体外增殖，且能够影响角朊细胞内cAMP水平、CaM、 NF-KB基因的表达，这和神经生长因子的作用环节高度切合，因此，我们认为“清热活血解毒法”用靶点可能不仅仅是某一条信号传导通路，而是做用于NGF及其受体形成上游干预，从而干预银屑病发病。

银屑病是一种多基因遗传背景下,受环多种境因素影响的免疫性皮肤疾病，其身心属性日益受到关注。作为神经内分泌免疫网络节点的神经生长因子在银屑病皮损处高表达，可刺激T细胞及角质形成细胞的增殖，参与多条信号传导通路，在银屑病发病过程中起关键作用。临床研究显示中医药治疗银屑病是具有一定优势，然而其治疗的作用机制却有待于深入研究。前期研究中，我们发现清热活血解毒方药的含药血清及部分中药单体可抑制多种银屑病相关细胞的体外增殖，且能够影响角朊细胞内cAMP水平、CaM、 NF-KB基因的表达，这和神经生长因子的作用环节高度切合，因此，我们认为“清热活血解毒法”用靶点可能不仅仅是某一条信号传导通路，而是做用于NGF及其受体形成上游干预，从而干预银屑病发病。实验结果表明：NGF在银屑病患者外周单核淋巴细胞及皮损表达量均明显高于正常人，而且经过 8 周活血解毒法治疗后，患者NGF的表达呈下降趋势。银屑病患者外周单核淋巴细胞中NGF受体TrKA、P75含量明显高于正常人，经治疗后 TrKA表达显著下降。患者皮损中 凋亡基因Bax 表达高于正常人，而 Bcl-xl 低于正常人，而经治疗后 Bax 有不同程度下降，Bcl-xl表达有不同程度升高。通过体外研究我们发现清热活血解毒方的主要有效单体（丹皮酚、紫草素、熊果酸、落新妇苷）能不同程度抑制 Hacat 细胞、Jurkat T细胞的增殖，并促进其凋亡，对NGF及其相关受体研究结果提示，不同的单体对于NGF受体的干预效应不尽相同。因此，我们认为NGF及其受体与银屑病发病的免疫机制相关，在银屑病发病过程中可能起了重要作用。