Mayer-da-Silva A, Gollnick H, Detmar M, Gassmüller J, Parry A, Müller R, Orfanos C E
Department of Dermatology, University Medical Center Steglitz, Free University of Berlin.
Acta Derm Venereol Suppl (Stockh). 1989;143:20-30.
The effects of azelaic acid (AZA) on the epidermis of 47 individuals (12 with normal skin, 15 with seborrheic skin and 20 suffering from acne) and on in vitro cultured keratinocytes are reported. Topical application of a 20% AZA cream significantly improved the lesions of acne patients, but failed to induce clinically detectable changes in normal or seborrheic epidermis. Complementary investigations clearly showed that AZA treatment failed to induce specific changes in sebum composition, excretion rate, or in the size of sebaceous glands, but modified epidermal keratinization. Keratohyalin granules and tonofilament bundles were reduced in size and number, mitochondria were swollen and the rough endoplasmic reticulum of malpighian keratinocytes enlarged. The infundibular epidermis of acne individuals showed marked reduction of the horny layer thickness, widening of the horny cell cytoplasm, transitional corneal cells, normalization of filaggrin distribution, and the comedo contained few bacteria and spores. In vitro, AZA exerted marked time- and dose-dependent antiproliferative cytostatic effects on cultured keratinocytes, with a 50% inhibitory dose of 20 mM, decreased some keratinocyte proteins (highly soluble fractions S2, keratohyalin macroaggregate R2, and non-cross-linked fibrous protein S4) and a 95 kD and a 35 kD protein of the cytosolic fraction. Mitochondria were frequently damaged and the rough endoplasmic reticulum enlarged. Our results indicate that AZA is an antikeratinizing agent, displaying antiproliferative cytostatic effects on keratinocytes and modulating the early and terminal phases of epidermal differentiation.
本文报道了壬二酸（AZA）对47名个体（12名皮肤正常、15名脂溢性皮肤和20名痤疮患者）表皮以及体外培养角质形成细胞的影响。局部应用20%的AZA乳膏可显著改善痤疮患者的皮损，但对正常或脂溢性表皮未引起临床可检测到的变化。补充研究清楚地表明，AZA治疗未能引起皮脂成分、排泄率或皮脂腺大小的特异性变化，但改变了表皮角化。透明角质颗粒和张力丝束的大小和数量减少，线粒体肿胀，马尔皮基角质形成细胞的粗面内质网增大。痤疮患者的漏斗部表皮显示角质层厚度明显减少，角质形成细胞胞质增宽，过渡性角膜细胞出现，丝聚合蛋白分布正常化，粉刺内细菌和孢子很少。在体外，AZA对培养的角质形成细胞具有明显的时间和剂量依赖性抗增殖细胞抑制作用，50%抑制剂量为20 mM，一些角质形成细胞蛋白（高可溶性组分S2、透明角质大聚集体R2和非交联纤维蛋白S4）以及胞质组分中的一种95 kD和一种35 kD蛋白减少。线粒体经常受损，粗面内质网增大。我们的结果表明，AZA是一种抗角化剂，对角质形成细胞具有抗增殖细胞抑制作用，并调节表皮分化的早期和终末期。
