皮肤光老化组织学改变研究进展

皮肤光老化是不断累积的日光照射所致的一个连续性过程,是指长期的日光照射(主要是紫外线)导致皮肤衰老.在组织学方面,表皮变化主要是角质形成细胞、黑素细胞、朗格汉斯细胞,真皮变化主要是弹力纤维变性和胶原减少.其机制主要涉及免疫系统、细胞因子改变、基质金属蛋白酶生成增加、活性氧簇增加及DNA损伤等.概述并探讨皮肤光老化组织学变化及其相应的发生机制.     

中波紫外线诱导皮肤角质形成细胞凋亡机制的研究进展

紫外线照射表皮后引起DNA损伤的表皮细胞通过日晒伤细胞(凋亡的角质形成细胞)的形成来清除。p53、Fas、Trp53等基因的表达促进角质形成细胞凋亡,而survivin的表达则抑制角质形成细胞凋亡。紫外线照射后皮肤可产生环丁烷嘧啶二聚体和6-4光产物,这两种光产物可以作为UVB诱导凋亡的起始信号。凋亡在清除DNA损伤的皮肤起着重要作用。在皮肤中通过凋亡清除DNA损伤的细胞,防止日光诱导癌变,而不是依赖于DNA损伤的校正修复。silibinin对中波紫外线引起人HaCaT永生化角质形成细胞凋亡具有双向调控作用。对UVB引起角质形成细胞凋亡的调控药物,值得进一步研究。     

紫外线辐射诱导角质形成细胞凋亡的机制

紫外线辐射诱导角质形成细胞凋亡,与多种皮肤病理过程关系密切,已引起人们关注。紫外线可通过诱导活性氧及细胞因子产生DNA损伤和基因表达改变等致角质形成细胞凋亡,此过程有多个信号转导途径参与,其中p53、CD95、Bcl-2、半胱天冬酶、丝裂原活化蛋白激酶介导的信号转导途径起重要作用。     

角质形成细胞的凋亡失调及相关皮肤病

角质形成细胞的凋亡在调节表皮发育和抑癌中起着关键作用，凋亡可平衡角质形成细胞的增殖来保持表皮厚度，促使角质层形成和清除恶化前细胞。除正常发展程序外，角质形成细胞的凋亡能被紫外线和其他刺激诱发，凋亡在保持皮肤细胞内环境稳定和一些皮肤病的发病机制中起着重要作用。     

皮肤光老化发生机制的研究进展

皮肤光老化是由于紫外线的长期慢性辐射损害而造成的皮肤损伤,在临床表现、组织病理学等方面与自然老化有着不同的表现.近年国内外关于光老化发生机制方面的研究有了很大的进展,研究已经证实,激活蛋白-1和核因子-кB活化导致基质金属蛋白酶的合成、线粒体损伤、蛋白质氧化和端粒在光老化发生中的作用.理解并认识这些发生机制有助于在防治慢性紫外线辐射造成的皮肤损伤方面提出新的预防和治疗策略.     

紫外线抑制免疫系统的研究进展

由于臭氧层损耗,使地球表面的紫外线辐射量增加。紫外线不但引起皮肤晒黑、红斑、色素沉着及光老化等急慢性皮肤损伤,而且通过影响朗格汉斯细胞的抗原提呈功能、诱导调节性T细胞形成、损伤DNA、影响角质形成细胞合成与释放细胞因子、影响尿刊酸代谢、神经内分泌等途径抑制皮肤免疫系统,最终发生皮肤肿瘤。     

Nrf2基因在紫外线氧化应激与光老化中的作用研究进展

皮肤是直接暴露于日光紫外线照射的人类器官,紫外线的照射可导致皮肤的多种损伤,如光老化以及各种皮肤肿瘤。重复的细胞光损伤是导致皮肤光老化的基础。研究发现,紫外线辐射于人体皮肤发生氧化应激反应,产生的活性氧簇(reactive oxygen species,ROS)是导致细胞光损伤的主要原因。Nrf 2在很多与氧化应激反应相关的病变中均发挥重要的防御保护作用,Nrf2缺失或激活障碍会增加细胞对紫外线辐射的敏感性,而加重细胞的光损伤以及光老化。该文综述了Nrf2基因在光损伤以及光老化中的重要保护作用。     

黄芪甲甙对中波紫外线损伤皮肤角质形成细胞的保护作用

目的 研究传统中药活性成分黄芪甲甙对中波紫外线(UVB)损伤皮肤角质形成细胞的保护作用.方法 采用30、60、90 mJ/cm2的UVB照射培养的人皮肤永生角质形成细胞系HaCaT细胞,加入黄芪甲甙进行干预处理,以MTT法检测细胞活性;ELISA法检测细胞因子肿瘤坏死因子(TNF-α)和白介素(IL)-6的分泌量;流式细胞仪检测细胞凋亡率.结果 UVB照射可引起皮肤角质形成细胞损伤,单纯照光组细胞增殖活性可下降23%～43%,而黄芪甲甙预处理组照光后活性仅下降7%～20%;UVB照射后炎性细胞因子TNF-α、IL-6分泌显著增加,A值分别为16.32～91.59及98.6～403.53,而黄芪甲甙预处理后其分泌量显著降低(P<0.05);UVB辐射后在G1期前出现明显的亚二倍体峰(凋亡峰),而经黄芪甲甙处理的UVB组细胞凋亡率则明显下降(P<0.05).结论　黄芪甲甙具有光保护性能,可减轻UVB对皮肤角质形成细胞的损伤作用.     

茶多酚对紫外线辐射后的角质形成细胞和成纤维细胞增生影响的保护作用

紫外线辐射(UVR)是皮肤生物性损伤的主要因素,而皮肤角质形成细胞和成纤维细胞是此生物损伤过程中受到影响的主要细胞[1]。本实验通过MTT法(四甲基偶氮唑盐)研究不同剂量的中波紫外线(UVB)和长波紫外线(UVA),对体外培养的人角质形成细胞株HaCaT和皮肤成纤维细胞增生的影响,并探讨具有抗氧化作用的茶多酚(teapolyphenol,TPP)对此影响的保护作用。1材料和方法1.1主要仪器和试剂酶联检测仪(Clinibio公司),紫外线辐照仪(Sigma公司,UVB光谱峰值为310～315nm,UVA为365nm),96孔培养板(Costar公司),DMEM培养基(Gibeco公司),小牛血清(杭…     

异丙嗪抑制中波紫外线辐射诱导HaCaT细胞产生白介素6

紫外线过量辐射是导致人类皮肤损伤的重要原因之一。角质形成细胞受到紫外线等外来因素刺激时,包括白介素6(IL-6)等多种细胞因子的分泌量增加^[1]。有研究证实组织胺可显著放大角质形成细胞对IL-6的基础分泌和紫外线辐射诱导的分泌^[2],而异丙嗪是一种H1受体阻滞剂,通过结合组织胺受体而发挥抗组织胺作用,故异丙嗪对紫外线诱导的角质形成细胞对IL-6的分泌可能有某种作用。本研究探讨异丙嗪对中波紫外线(UVB)辐射诱导HaCaT细胞产生IL-6的抑制作用。     

皮肤光老化机制研究进展

光老化指皮肤由于反复光暴露引起的提前老化,其发生机制涉及细胞内信号转导通路、细胞表面细胞因子和表皮生长因子受体的活化,活性氧族是激发细胞信号转导过程中的重要介质,其结果导致基质金属蛋白酶合成增加,从而使真皮纤维结缔组织过度降解和弹性纤维变性,同时真皮胶原的合成亦减少,角质形成细胞、成纤维细胞及炎症浸润细胞等多种细胞参与光老化过程.     

皮肤光老化机制研究进展

光老化指皮肤由于反复光暴露引起的提前老化,其发生机制涉及细胞内信号转导通路、细胞表面细胞因子和表皮生长因子受体的活化,活性氧族是激发细胞信号转导过程中的重要介质,其结果导致基质金属蛋白酶合成增加,从而使真皮纤维结缔组织过度降解和弹性纤维变性,同时真皮胶原的合成亦减少,角质形成细胞、成纤维细胞及炎症浸润细胞等多种细胞参与光老化过程.     

Effect of aging and habitual sun exposure on the genetic response of cultured human keratinocytes to solar-simulated irradiation.

Aging and chronic sun exposure are known to be associated with decreased cutaneous immune function, changes in the balance between epidermal proliferation and differentiation, and a greatly enhanced risk of photocarcinogenesis. However, their specific effects on the response of human keratinocytes to ultraviolet (UV) irradiation are unknown. We therefore asked whether aging and photoaging modulate the response at the mRNA level to UV-inducible genes implicated in immunomodulation and/or growth control. Cultured human keratinocytes derived from newborn, young adult, and old adult donors were exposed to a single physiologic dose of solar-simulated UV or sham irradiation and harvested at 1, 4, 8, 24, and 48 h post-irradiation for northern blot analysis. Specific mRNA was detected using cDNA probes encoding the proto-oncogenes c-fos and c-myc and the growth-arrest and DNA damage (GADD153) gene, all recently shown by our laboratory to be modulated by UV in newborn keratinocytes; interleukin (IL)-1a, IL-1b, and the IL-1 receptor antagonist (IL-1ra), two keratinocyte cytokines and their competitive inhibitor, implicated in the immunomodulatory effect of UV; and SPR2, a recently cloned gene known to be induced during normal keratinocyte differentiation and by lethal UV-C irradiation. Our data suggest that aging alone strikingly increases the baseline expression of SPR2 and IL-1ra but has relatively little effect on the response to UV for the other genes examined. In contrast, the combination of aging and habitual sun exposure, so-called photoaging, markedly increases c-fos inducibility and decreases baseline expression of SPR2 and IL-1ra relative to that in cells from sun-protected skin of the same donors. The implied alterations in signal transduction and differentiation state observed in cells derived from habitually sun-exposed sites of old adults may explain in part the predisposition to photocarcinogenesis in photoaged skin.     

海洋生物提取物中抗皮肤光老化活性成分的研究进展

 海洋生物是海洋资源的重要组成部分,具有抗菌、抗氧化、抗炎及光保护等生物活性,在医用护肤品和药物的生产中有重要的贡献。长期紫外线照射是皮肤外源性老化的主要原因。紫外线照射可损伤表皮角质形成细胞和真皮成纤维细胞,引起皮肤萎缩、皱纹及皮肤肿瘤等。海洋生物中有众多光保护物质,包括类菌孢素氨基酸、硫酸多糖、类胡萝卜素和多酚类物质等,这些物质在皮肤护理、化妆品和医药产品中有很大的开发潜力。本文综述了近年来海洋生物中的光保护物质及其在皮肤光老化中的应用进展。     

Chronic actinic damage of facial skin

Chronic actinic damage of the skin manifests itself as extrinsic skin aging (photoaging) and photocarcinogenesis. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms of photoaging. DNA photodamage and ultraviolet-generated reactive oxygen species are the initial events that lead to most of the typical histologic and clinical manifestations of chronic photodamage of the skin. Chronic actinic damage affects all layers of the skin. Keratinocytes, melanocytes, fibroblasts, and endothelial cells are altered by ultraviolet radiation and can result in numerous changes in human skin, particularly the skin of fair-skinned individuals. These changes include actinic keratosis, thickening and wrinkling, elastosis, telengiectasia, solar comedones, diffuse or mottled hyperpigmentation, and skin cancers. There are many options in the treatment of changes caused by chronic actinic damage. The most effective measure of prevention of the photoaging and photocarcinogenesis is sun protection.     

Effects of 12-O-tetradecanoyl-phorbol-13-acetate [corrected] and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged human keratinocytes.

Skin aging may be divided into photoaging and intrinsic aging. The purpose of this study was to investigate the effects of 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged skin, compared with young skin. Keratinocytes were taken from newborns, young adults in their twenties, and from the forearm and thigh of volunteers in their fifties and seventies. Interleukin-1alpha and -6, and interleukin-1 receptor antagonist, c-fos and c-myc were measured after cultured keratinocytes had been treated with 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate. There has been no report concerning the dependence of cytokine production by sodium lauryl sulfate upon photoaging and intrinsic aging. This study also involves the first investigation of the effects of aging on c-myc expression by 12-O-tetradecanoyl-phorbol-13-acetate treatment. Cytokine production decreased markedly with age. These results suggest the progressive decline of cellular function with age. The ratio of cytokine production in the irritant-treated group compared with that in the control group showed a different pattern in photoaging and intrinsic aging. With the significant difference between photoaging and intrinsic aging, T/C ratio decreased in interleukin-1alpha and interleukin-1 receptor antagonist upon aging, whereas it increased in interleukin-6. S/C ratio was uniquely elevated on photoaged skin in the 50 y age group. It is suggested that photoaged skin shows an exaggerated reaction to surfactant. Compared with the control, c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes decreased with age in the thigh, but increased in the photoaged skin of forearm. The increased c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes could be relevant for the predisposition of photoaged keratinocytes to malignant transformation.     

Photosensitized growth inhibition of cultured human skin cells: mechanism and suppression of oxidative stress from solar irradiation of glycated proteins

Chronic exposure to sunlight plays a role in skin aging and carcinogenesis. The molecular mechanisms of photodamage by ultraviolet A, the sunlight's major ultraviolet constituent, are poorly understood. Here we provide evidence that advanced glycation end products on proteins are sensitizers of photo-oxidative stress in skin cells. Glycation is a process of protein damage by reducing sugars and other reactive carbonyl species leading to the formation of advanced glycation end products, which accumulate on long-lived proteins such as dermal elastin and collagen during skin aging. Growth inhibition as a result of advanced glycation end product photosensitization of ultraviolet A and solar-simulated light was demonstrated in human keratinocytes and fibroblasts. Using advanced glycation end product bovine serum albumin and advanced glycation end product collagen as model photosensitizers, ultraviolet A-induced formation of H2O2 was identified as the key mediator of skin cell growth inhibition as evidenced by complete protection by catalase treatment and equivalent growth inhibition of unirradiated cells treated with pre-irradiated advanced glycation end product protein. D-penicillamine protected against advanced glycation end product-photosensitized growth inhibition even when added following irradiation, suggesting the feasibility of therapeutic approaches for protection against skin ultraviolet A damage. Photosensitized growth inhibition increased with the degree of advanced glycation end product modification paralleled by the amount of H2O2 formed upon solar-simulated light irradiation of the protein. Photosensitization was not observed using bovine serum albumin modified with the major advanced glycation end product, Nepsilon-carboxymethyl-L-lysine, ruling out effects of cellular advanced glycation end product receptor (RAGE) stimulation. In contrast to bovine serum albumin, unglycated collagen showed photosensitization in CF3 fibroblasts and generation of H2O2 upon solar-simulated light irradiation. This study supports the hypothesis that advanced glycation end product-modified proteins are endogenous sensitizers of photo-oxidative cell damage in human skin by ultraviolet A-induced generation of reactive oxygen species contributing to photoaging and photocarcinogenesis.     

与紫外线致皮肤损伤相关的部分信号通路研究进展

紫外线照射可使皮肤损伤,导致皮肤光老化或皮肤肿瘤.多个信号通路如Nrf2-Keap1-ARE、核因子κB、丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3激酶-丝氨酸/苏氨酸激酶-西罗莫司靶蛋白(PI3K-AKt-mTOR)信号通路等参与皮肤光老化和(或)皮肤肿瘤的发病.Nrf2信号通路在氧化应激状态下开启,有维持氧化还原平衡和参与细胞新陈代谢等作用.核因子κB信号通路的激活引起基质金属蛋白酶等水平上调,与皮肤老化和非黑素性皮肤癌有关.MAPK信号通路参与皮肤老化和皮肤肿瘤的进展.PI3K-AKt-mTOR信号通路主要与皮肤肿瘤相关.紫外线照射可诱导上述通路的活化,参与皮肤光老化或皮肤肿瘤的发生发展.对上述通路的进一步研究有望为抵御皮肤的光老化和皮肤肿瘤提供新的方法.     

In vivo fluorescence of human skin. A potential marker of photoaging

Fluorescence is a feature of elastin and collagen, both major compounds of human dermis that are altered by age and photoexposure. We studied the intrinsic fluorescence of skin in vivo in 28 human volunteers to determine whether photoaging and chronologic aging of the skin could be evaluated by this noninvasive technique. We demonstrate that the excitation of skin autofluorescence by laser ultraviolet radiation yields characteristic tissue fluorescence spectra that are unrelated to age, pigmentation, or skin thickness. The differences in skin autofluorescence appear to be related to photoexposure. Thus, laser-induced fluorimetry, a noninvasive technique, may be adaptable as a marker of photoaging.