基于逆转TSLP-LCs介导的Th1/Th2失衡研究沙棘果油对AD小鼠皮肤屏障的修复作用

The prevalence of atopic dermatitis (AD) is increasing in recent years in China. As a first-line therapy, topical glucocorticoid application causes serious side effects. It’s great significants in finding a safe and effective treatment. Skin barrier repair plays a key role in AD treatment. Results of our researches have showed that sea buckthorn pulp oil given by gavage had protective effects on skin barrier in mice with AD, but the mechanisms still remain unclear. Thymic stromal lymphopoietin (TSLP) is overexpressed in epidermis in patients with AD, TSLP can activate Th2 immunoreaction mediated by the langerhans cells (LCs), and immoderate Th2 immunoreaction aggravates impairment of skin barrier function by inhibiting expressions of skin barrier proteins. we put forward the hypothesis that sea buckthorn pulp oil given by gavage can inhibit secretion of TSLP by its repair effects on epidermal cells, and can recover normal phenotype and function of LCs, consequently, immoderate Th2 immunoreaction can be inhibited. The recovery Th1/Th2 balance can increase the expressions of skin barrier proteins, which can promote the skin barrier repair. The main objective of this study is to elucidate mechanisms of protective effects of sea buckthorn pulp oil and its effective components on skin barrier, based on its effects on Th1/Th2 imbalance mediated by TSLP-LCs. The study will provide experimental evidences for AD therapies.

特应性皮炎（AD）发病率在我国呈明显上升趋势，作为一线疗法，局部外用糖皮质激素治疗副作用大，亟待找到更为安全有效的治疗方法。修复皮肤屏障是AD治疗的关键环节，我们前期研究结果表明灌胃沙棘果油对AD小鼠皮肤屏障具有修复作用，机制有待进一步研究。AD患者表皮细胞过度表达胸腺基质淋巴细胞生成素（TSLP），TSLP可启动朗格汉斯细胞（LCs）调控的Th2型反应，过度的Th2型反应可通过抑制皮肤屏障蛋白表达等机制导致皮肤屏障功能障碍。我们提出科学假说：沙棘果油可通过修复表皮细胞抑制其释放TSLP，恢复LCs正常的表型与功能，从而抑制过度的Th2型反应；通过恢复Th1/Th2平衡促进皮肤屏障蛋白的表达，修复被破坏的皮肤屏障。本项目拟结合体内外实验，基于沙棘果油及其有效成分对TSLP-LCs介导的Th1/Th2失衡状态的影响，阐明沙棘果油对AD小鼠皮肤屏障的修复机制，为寻找新的AD治疗手段提供依据。

特应性皮炎（atopic dermatitis, AD）发病率在我国呈明显上升趋势，作为一线疗法，局部外用糖皮质激素治疗副作用大，亟待找到更为安全有效的治疗方法。修复皮肤屏障是AD治疗的关键环节，我们前期研究结果表明灌胃沙棘果油对AD小鼠皮肤屏障具有修复作用，机制有待进一步研究。AD患者表皮细胞过度表达胸腺基质淋巴细胞生成素（TSLP），TSLP可启动朗格汉斯细胞（LCs）调控的Th2型反应，过度的Th2型反应可通过抑制皮肤屏障蛋白表达等机制导致皮肤屏障功能障碍。本项目基于TSLP-LCs介导的Th1/Th2平衡研究了沙棘果油对AD小鼠模型的干预作用及机制。研究结果表明，灌胃沙棘果油可显著减轻皮炎评分，抑制耳朵肿胀程度，减少肥大细胞浸润。沙棘果油还降低了皮损组织IL-4、IFN-γ、TNF-α和TSLP的表达。此外沙棘果油还可抑制LCs细胞从皮损向引流淋巴结的迁移。本项目结合体内外实验，基于沙棘果油及其有效成分对TSLP-LCs介导的Th1/Th2失衡状态的影响，阐明沙棘果油对AD小鼠皮肤屏障的修复机制，可为寻找新的AD治疗手段提供依据。