反向痤疮(AI)是一种复发性炎症性皮肤病，多在青春期后发病，常因反复脓肿窦道瘘管致毁容或失能，因无理想的治疗，研究其发病机制非常迫切。现认为有遗传及雄激素等致病因素，且毛囊最早受累。之前在一个AI家系中，我们发现患者γ-分泌酶亚基NCT的编码基因NCSTN异常突变，且患者皮损毛囊部位NCT较正常人表达降低，雄激素受体(AR)则升高。我们假设青春期在雄激素作用下，毛囊生长发育明显增强，其间需要γ-分泌酶信号通路支持，但因NCSTN突变使该通路障碍，引起毛囊生长发育异常导致毛囊闭塞，拉开AI发病的序幕。本研究拟用NCSTN突变小鼠，通过Real-Time PCR、Western Blot、免疫荧光及电镜方法，研究NCSTN突变能否引起上述信号通路障碍，继而出现毛囊异常，以及该异常能否被AR阻滞剂所改善，以揭示NCSTN突变及雄激素在AI发病中的作用，为探索AI发病机制和临床治疗提供思路和支持。

Acne inversa (AI) is a relapsing and inflammatory disorder of the skin, the onset is often after the adolescence, the recurrent abscesses with Sinus tracts and fistula lead to disfigurement and even disability. The study on its pathogenesis become more important because there is no effective treatment on AI today. The genetic and androgen factors are considered as the etiologies at present, and the hair follicles are involved in the early stage. The mutation of gene NCSTN coding γ-secretase subunit NCT in an AI family was identified in our early study, and the expression of NCT in hair follicle is lower in AI patients than it in normal controls, but the androgen receptor (AR) is inverse. We postulate that the proliferation and differentiation of hair follicles heighten under the more action of androgen in adolescence, and the signaling pathways downstream of γ-secretase are required in this stage, but no enough supports are supplied for the dysfunction of γ-secretase because of the mutation in gene NCSTN. Thus the failure of proliferation and differentiation and occlusion in hair follicles occur. We plan to study the changes of hair follicles after the mutation of gene NCSTN in mouse according to Real-Time PCR, Western Blot, immunofluorescence and electron microscopy. We want to know whether the dysfunction of signaling pathways downstream of γ-secretase resulted from NCSTN mutation, then whether the abnormalities of proliferation and differentiation in hair follicles occur, and whether these abnormalities in hair follicles are improved by the action of androgen receptor blocker. For the purpose of finding the action of NCSTN mutation and androgen in AI, this study will contribute to the pathogenesis of AI and provide support for the clinical treatment.