中文摘要
银屑病的发生与角质形成细胞(KC)密切相关。临床实验证实,β-AR(肾上腺素受体)阻滞剂能降低cAMP,加重病情。麻黄-桂枝“药对”作为发汗方中的经典药对,研究表明,其具有类β-AR激动剂作用。我们前期实验首次证实了该“药对”能够干预BALB/c小鼠银屑病样模型的疾病进程,减轻豚鼠银屑病样模型的皮损程度。因KC上AR恰好只表达为β-AR,故我们提出假说:麻黄-桂枝“药对”可能是通过介导β-AR/cAMP/PKA信号通路发挥药效。本研究拟用β-AR阻滞剂进行豚鼠造模并用IL-22和IL-17诱导HaCaT细胞,从体内和体外两个方面观测该“药对”对疾病模型动物的疗效,对细胞增殖、分化、凋亡、分泌趋化因子的影响及与β-AR/cAMP/PKA通路的相关性,以期阐明麻黄-桂枝“药对”治疗银屑病的可能机制和靶点,为“其在皮者,汗而发之”理论的临床运用提供客观依据。
英文摘要
The occurrence of psoriasis are closely related with keratinocyte(KC).Clinical trials has confirmed that beta AR (adrenaline receptor) blockers can reduce cAMP and aggravate illness. “Mahuang-Guizhi” herbal pair as the classical medicine for diaphoresis, studies have shown that its had similar beta AR agonist. Our preliminary experiments have confirmed for the first time that the herbal pair had the function to intervene the process in the BALB/c mice psoriasis sample model,reduce the guinea pig model psoriatic lesion. AS only beta AR exist on KC, we hypothesized that “Mahuang-Guizhi” herbal pair may play efficacy by mediating beta AR/cAMP/PKA signaling pathways.This study will use beta AR blockers to build guinea pigs model for the in vitro studies. Use IL-22 and IL-17 to induce HaCaT cells for the in vivo studies. From two aspects to observe the curative effect of animal disease model, and the cell proliferation, differentiation, apoptosis as well as the chemokines secreation.And to explore the relation with the beta AR/cAMP/ PKA pathways. We expect to clarify the possible mechanisms and targets of “Mahuang-Guizhi” herbal pair in the treatment of psoriasis, and provide objective basis for the clinical use of the theory-"in the skin, use diaphoresis method ".
