当归饮子通过调控T细胞自噬治疗慢性荨麻疹的作用及机制研究

Currently, the traditional Chinese medicine Dang Gui Yin Zi is frequently used in clinical treatment of chronic urticaria, and has expressed satisfactory therapeutic effect on it. However, few scientific evidence have been found for the effect. Studies revealed that helper T cells dysfunction was a key factor in inducing allergic diseases, and autophagy was an important defence and protection action of eukaryotic cells. Our preliminary research found that Dang Gui Yin Zi could regulate the T cells' functions so that to slow down the development of chronic urticaria. From that, we proposed a hypothesis that there might be T-cell autophagy in the progression of chronic urticaria. Moreover, Dang Gui Yin Zi might regulate the the autophagy of T cells, which finally improves the Th1/Th2 imbalance. We intended to establish a rat model of urticaria-like allergic, in which, the expression, function variation and autophagy of T cells would be observed. Besides, the effect and potential mechanism of Dang Gui Yin Zi on T cells' autophagy would be explored. The prospective results would provide new directions and targets for the prevention and treatment of chronic urticaria, as well as the mechanism exploration of traditional Chinese medicine.

慢性荨麻疹是一种常见的过敏性皮肤病。中医药当归饮子方是目前治疗慢性荨麻疹的常用方剂之一，在防治荨麻疹的发作上有较好的作用，但缺乏治疗慢性荨麻疹的现代科学证据支撑。研究表明，辅助性T细胞失衡是诱发变态反应性疾病的关键因素。自噬是真核细胞的一种防御和保护机制，具有重要意义。我们前期研究发现，当归饮子能通过调节T细胞功能减缓慢性荨麻疹的发生发展，所以我们提出假设，慢性荨麻疹的进展过程中可能存在T细胞的自噬现象，并且中药当归饮子可能通过调控T细胞的自噬，改善Th1 /Th2失衡。我们拟于在大鼠荨麻疹样过敏模型上，观察T细胞表达、功能的变化及自噬的情况；明确当归饮子在诱导T细胞自噬中的作用及可能的作用机制。为慢性荨麻疹的防治和药物的开发提供新的思路和靶点，为中医药防治荨麻疹的机理开辟一个新方向。

本课题采用现代技术方法和T细胞自噬来阐释中医基础理论“少阴有余”的物质基础，探索当归饮子防治荨麻疹的现代科学本质，阐明自噬在荨麻疹发作过程中的变化以及当归饮子对自噬的影响，从细胞自噬角度揭示当归饮子防治荨麻疹的分子机制，推动中医治法与病证疗效原理相结合的现代研究。 .本研究将 70 只 SD 大鼠、70 只基因敲除小鼠随机分为空白组、模型组、中药对照组、西药对照组、高剂量组、中剂量组、低剂量组予以干预，结果提示荨麻疹样病理改变形成，IL-23表达上调，自噬标志物 LC3B、beclin-1 蛋白表达升高，且 LC3B、beclin-1 蛋白表达趋势与自噬的形成、降解过程相一致；提示炎症因子活跃和自噬水平升高在慢性荨麻疹的发病中有重要作用，而当归饮子组可显著下调IL-23水平，上调自噬标志物 LC3B、beclin-1 水平。.综上，当归饮子对荨麻疹动物模型的干预作用的产生可能与下调皮肤中IL-23表达，上调自噬标志物 LC3B、beclin-1 水平，促进自噬体形成相关，表明当归饮子促进自噬水平的增强，且加速自噬内容物的降解，当归饮子可能通过对细胞自噬水平的调控作用实现防治荨麻疹的发作。