Feingold K R, Man M Q, Proksch E, Menon G K, Brown B E, Elias P M
Dermatology Service, Veterans Administration Medical Center, San Francisco, California 94121.
J Invest Dermatol. 1991 Feb;96(2):201-9. doi: 10.1111/1523-1747.ep12461153.
Recent studies have linked epidermal cholesterol synthesis with maintenance of the permeability barrier. To assess directly the importance of cholesterol synthesis, we applied lovastatin, a potent inhibitor of cholesterol synthesis, to hairless mouse skin. Transepidermal water loss (TEWL) began to increase after four to six daily applications. Co-application of cholesterol blocked the expected increase in TEWL, demonstrating the importance of cholesterol for development of the lesion. The histology of lovastatin-treated skin revealed epidermal hyperplasia, accompanied by accelerated DNA synthesis. Whereas cholesterol synthesis initially was reduced in lovastatin-treated epidermis, with further treatment cholesterol synthesis normalized, while fatty acid synthesis accelerated greatly. Although the total free sterol content of lovastatin-treated epidermis remained normal, the fatty acid content increased coincident with barrier disruption. Finally, morphologic abnormalities of both lamellar body structure and their deposited, intercellular contents occurred coincident with the emerging biochemical abnormalities. Thus, the abnormal barrier function in this model can be ascribed to an initial inhibition of epidermal sterol synthesis followed by an alteration in cholesterol and fatty acid synthesis, leading to an imbalance in stratum corneum lipid composition and abnormal membrane bilayer structure.
近期研究已将表皮胆固醇合成与渗透屏障的维持联系起来。为了直接评估胆固醇合成的重要性，我们将胆固醇合成的强效抑制剂洛伐他汀应用于无毛小鼠皮肤。每日应用四至六次后，经表皮水分流失（TEWL）开始增加。同时应用胆固醇可阻止TEWL预期的增加，这表明胆固醇对损伤发展的重要性。洛伐他汀处理的皮肤组织学显示表皮增生，并伴有DNA合成加速。虽然在洛伐他汀处理的表皮中胆固醇合成最初减少，但随着进一步处理，胆固醇合成恢复正常，而脂肪酸合成则大幅加速。尽管洛伐他汀处理的表皮中总游离甾醇含量保持正常，但脂肪酸含量随着屏障破坏而增加。最后，板层小体结构及其沉积的细胞间内容物的形态学异常与新出现的生化异常同时出现。因此，该模型中异常的屏障功能可归因于表皮甾醇合成的初始抑制，随后胆固醇和脂肪酸合成发生改变，导致角质层脂质组成失衡和膜双层结构异常。
