Mao-Qiang M, Brown B E, Wu-Pong S, Feingold K R, Elias P M
Dermatology Service, Veterans Affairs Medical Center, San Francisco, USA.
Arch Dermatol. 1995 Jul;131(7):809-16. doi: 10.1001/archderm.131.7.809.
Although barrier function requires cholesterol, free fatty acids, and ceramides, applications of one or two of these lipids to damaged skin impedes barrier recovery, while equimolar mixtures allow normal recovery. Both incomplete and complete mixtures appear to be internalized within the epidermal nucleated layers, followed by the secretion of abnormal vs normal lamellar body contents, respectively. We compared the ability of complete physiologic lipid mixtures vs a nonmetabolized hydrophobic lipid, petrolatum, to repair the barrier and the requirement for intracellular processing of these lipids within the epidermis.
Neat petrolatum, which remains restricted to the stratum corneum, produces more rapid improvement in barrier function than the solvent-dispersed physiologic lipids, and its effects are not altered by coapplication of either monensin or brefeldin A (both from Sigma Chemical Co, St Louis, Mo), known inhibitors of exocytosis and organellogenesis, respectively. In contrast, the physiologic lipids enter the nucleated layers in substantial amounts and require longer to produce barrier recovery. Whereas monensin blocks their ability to facilitate barrier recovery, the physiologic lipids overcome brefeldin A-induced delays in barrier recovery, bypassing the subcellular site of brefeldin A blockade, normalizing both lamellar body contents and intercellular bilayers.
While petrolatum remains restricted to the stratum corneum, physiologic lipid mixtures influence barrier recovery after transport to subjacent, nucleated layers, followed by internalization, apparent transport to the distal Golgi apparatus, and incorporation into nascent lamellar bodies.
尽管屏障功能需要胆固醇、游离脂肪酸和神经酰胺,但将其中一种或两种脂质应用于受损皮肤会阻碍屏障修复,而等摩尔混合物则能使屏障正常恢复。不完全混合物和完全混合物似乎都会被内化到表皮有核层内,随后分别分泌异常和正常的板层小体内容物。我们比较了完全生理脂质混合物与一种非代谢性疏水脂质凡士林修复屏障的能力,以及表皮内这些脂质进行细胞内加工的需求。
纯凡士林局限于角质层,与溶剂分散的生理脂质相比,其能更快改善屏障功能,且分别作为已知的胞吐作用抑制剂和细胞器生成抑制剂的莫能菌素或布雷菲德菌素A(均购自密苏里州圣路易斯市的西格玛化学公司)共同应用时,凡士林的效果不会改变。相比之下,生理脂质大量进入有核层,且需要更长时间才能实现屏障恢复。虽然莫能菌素会阻断它们促进屏障恢复的能力,但生理脂质能克服布雷菲德菌素A诱导的屏障恢复延迟,绕过布雷菲德菌素A阻断的亚细胞位点,使板层小体内容物和细胞间双层都恢复正常。
凡士林局限于角质层时,生理脂质混合物在转运至下方的有核层、随后被内化、明显转运至远端高尔基体并整合到新生板层小体后,会影响屏障恢复。