增生细胞核抗原在亚急性或慢性皮炎表皮增生模型中的表达
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摘要
目的:皮肤的屏障功能对角质细胞DNA的合成具有调节作用,在急性动物模型中,当屏障功能降低时,表皮细胞DNA的合成增加,其增加的程度与屏障功能异常的程度成正比,当屏障功能改善后,由屏障功能异常所诱导的DNA的合成受到相应的抑制。亚急性及慢性皮炎的主要病理改变是表皮增生过度;生理改变是表皮屏障功能降低,但亚急性及慢性皮炎表皮增生过度与屏障功能改变的相关性,目前尚无此方面的研究。本实验的目的是分别以0.5%2,4二硝基氟苯(DNFB)及0.01%佛波酯(TPA)造亚急性及慢性皮炎的动物模型,并通过加用非通透性的膜覆盖及涂擦保湿剂硅油来改善表皮屏障功能,以普通组织病理及增生细胞核抗原(PCNA)的表达来评价表皮增生是否改变,进而推断表皮屏障功能改变是否与亚急性或慢性皮炎的表皮增生有关。
方法:将小鼠随机分成A、B、C三组,每组分为1、2、3小组,其中A组乙醇组,B组2,4二硝基氟苯组(DNFB)、C组佛波酯组(TPA);1设为基质组,2设为保鲜膜组,3设为硅油组,分别计为A1、A2、A3;B1、B2、B3;C1、C2、C3。A1组(乙醇基质组)为单纯外搽90%乙醇,A2组(乙醇保鲜膜组)为外搽90%乙醇后加用保鲜膜覆盖,A3组(乙醇硅油组)为外搽90%乙醇后涂擦硅油; B1组(DNFB基质组)为单纯外搽0.5% DNFB,B2组为(DNFB保鲜膜组)为外搽0.5% DNFB后加用保鲜膜覆盖,B3组(DNFB硅油组)为外搽0.5% DNFB后涂擦硅油; C1组( TPA基质组)为单纯外搽0.01% TPA ,C2组(TPA保鲜膜组)为外搽0.01% TPA后加用保鲜膜覆盖,C(3TPA硅油组)为外搽0.01% TPA后涂擦硅油。各组经除毛后,第1天及第2天每日仅在B组的腹、背部涂擦1次,每次70微升,自第7天开始,每组均用相应的制剂治疗,每隔2日一次,每次70微升,加用保鲜膜组在涂相应制剂30分钟后于涂药区加盖保鲜膜,涂擦硅油组在涂相应制剂30分钟后于涂药区涂擦硅油,每日2次,造膜期为25天。实验结束后,于各组动物的腹、背部取小鼠皮肤活检,分别做普通病理(HE染色)及PCNA的免疫组化染色,在显微镜相同放大倍数下,测量各组表皮的厚度,计算均值;观察表皮细胞PCNA的染色,计数表皮PCNA阳性细胞数,计算PCNA阳性标记率,并计算均值,分别进行统计学分析。
结果:实验动物大体观察显示乙醇各组动物皮肤无潮红、增厚;DNFB各组动物皮肤轻度潮红、粗糙、增厚,个别部位稍有渗出、结痂,呈亚急性皮炎表现;TPA各组动物皮肤轻度潮红、表皮干燥、增厚,呈慢性皮炎表现。
组织病理显示乙醇各组未见表皮增厚,未见真皮内炎症细胞浸润,且各组PCNA阳性细胞表达仅限于基底细胞层;DNFB各组及TPA各组表皮明显增厚,真皮内较多量炎症细胞浸润,DNFB组及TPA组的PCNA阳性细胞表达分布于表皮的中下层包括基底细胞层和棘细胞层,其表达数量及表达厚度较乙醇各组均明显增加。DNFB基质组、TPA基质组分别比较乙醇基质组其表皮增生厚度及PCNA阳性标记率均在统计学上有显著性差异,P<0.05,亚急性皮炎、慢性皮炎表皮增生模型成功。DNFB保鲜膜组较DNFB基质组其表皮增生厚度及PCNA阳性标记率在统计学上未见显著性差异(P>0.05);DNFB硅油组较DNFB基质组其表皮增生厚度及PCNA阳性标记率在统计学上亦未见显著性差异(P>0.05)。
TPA保鲜膜组较TPA基质组其表皮增生厚度及PCNA阳性标记率在统计学上未见显著性差异(P>0.05);TPA硅油组较TPA基质组其表皮增生厚度及PCNA阳性标记率在统计学上亦未见显著性差异(P>0.05)。
结论:1.利用0.5%2,4二硝基氟苯(DNFB)及0.01%佛波酯(TPA)反复涂擦小鼠背部可以复制亚急性或慢性皮炎的模型。2.增生细胞核抗原在亚急性皮炎或慢性皮炎的动物模型中的表达明显增高。3.应用非通透性的膜覆盖及涂擦保湿剂硅油对亚急性及慢性皮炎小鼠模型的表皮增生没有明显的调节作用。
Objective: Epidermal barrier function would adjust the combination of keratinocyte DNA. In acute animal models, the combination of keratinocyte DNA will be increased while the epidermal barrier function degrades and the increasing extent is in direct retio with the degree of the normal barrier function. When the epidermal barrier function is improved, the combination of keratinocyte DNA will be restrained.The main feature of tissue pathology is epidermal over-proliferation and physiology chang is that epidermal barrier function degrades in the model of subacute and chronic dermatitis. At present , there is no study of relationships between epidermal barrier function and epidermal proliferation in model of subacute and chronic dermatitis. In the experiment, we eastablished models by application of 0.5%2,4-dinitro-1-flucrobenzene (DNFB) and 0.01% TPA on mouse backs. Epidermal barrier function was improved by covering with airtight memberance and repeated application of silicon oil on the models . Tissue pathology and expression of proliferation cell nuclear antigen [PCNA (pc10)] are used to assess whether epidermal proliferation was changed or not. Then we can draw a conclusion about whether epidermal barrier function is realated with epidermal proliferation in the model of subacute and chronic dermatitis.
Methods: The mouse were devided into there groups at random named with A,B,C .Every group was devided into subgroup named with 1,2,3. So we have 6 groups marked with A1,A2,A3;B1,B2,B3;C1,C2,C3. A-group is alcohol group. B-group is 0.5%2,4-dinito-1-flucrobene (DNFB) group. C-group is TPA group. Subgroup1 is control group. Subgroup2 is airtightmemberance group. Subgroup3 is silicon oil group. In the experiment, the application of 90% alcohol was only taken in A1 group mouse (alcohol-control group). The mouse were covered with airtight memberance after application of 90% alcohol in A2 group (alcohol- airtight memberance group). The mouse were applicated with silicon oil after 90% alcohol in A3 group (alcohol- silicon oil group). The application of 0.5% DNFB was only taken in B1 group mouse(DNFB -control group). The mouse were covered with airtight memberance after application of 0.5% DNFB in B2 group (DNFB - airtight memberance group). The mouse were applicated with silicon oil after 0.5% DNFB in B3 group (DNFB - silicon oil group). The application of 0.01% TPA was only taken in C1 group mouse (TPA -control group). The mouse were covered with airtight memberance after application of 0.01% TPA in C2 group (TPA - airtight memberance group). The mouse were applicated with silicon oil after 0.01% TPA in C3 group(TPA - silicon oil group). After the mouse fur were removed on the belly and back, Only B-group mouse were applicated with 70μl 0.5% DNFB once a day on the first and second day. From the seventh day, all groups were applicated with the right preperation 70μl once two days. In airtight memberance groups, the mouse skin was coverd with airtight memberance after the right preperation was applicated 30 minutes later. In silicon oil group, silicon oil was daubed on the skin after the right preperation was applicated 30 minutes later, twice aday. It took 25 days to mak ethe models. After the models were established, the tissue samples were taken and examined by pathology and immunnohistochemically stained examined with monodonal antibody [PCNA (pc10)] technique. The skin thickness of each sample was examined and the PCNA-positive cells were observed under the same multiple microscope. The average data was calculated and the statistic analysis was achieved.
Results: Tissue pathology shows that epidermal tickness did not changed and inflammation cells were not found in dermis. PCNA-positive cells were only expressed on stratum basalum in alcohol groups. Epidermal tickness increased obviously and there were more inflammation cells in dermis on the model of DNFB and TPA .PCNA-positive cells expressed not only on stratum basalum but also on the middle-low stratum spinosum inDNFB and TPA groups and PCNA-positive cells expressed more obviously. That means that epidermal tickness and the level of PCNA expression increased obviously in the model of DNFB and TPA groups than alcohol groups. There were remarkably statistical differences on epidermal tickness and the level of PCNA in the model of DNFB-control and TPA-control group compared with alcoho-control group (P<0.05). So the models of epidermal proliferation in subacute and chronic dermatitis were successed.
There were no statistical differences on epidermal tickness and the level of PCNA between the model of DNFB-airtight memberance and DNFB-control group(P>0.05). The same result came out between the model of TPA- airtight memberance and TPA-control group( P>0.05).There were no statistical differences on epidermic tickness and the level of PCNA between the model of silicon oil and control groups in DNFB and TPA (P>0.05).
Conclusion: 1. Repeated application of 0.5% DNFB and 0.01%TPA on the mouse back can make copies of the models of epidermal proliferation in subacute and chronic dermatitis. 2. The level of PCNA expression was increased obviously in the model of subacute and chronic dermatitis. 3. Covering with airtight memberance and application of silicon oil on mouse backs can not effectively adjust the epidermal proliferation in the model of subacute and chronic dermatitis.
方法:将小鼠随机分成A、B、C三组,每组分为1、2、3小组,其中A组乙醇组,B组2,4二硝基氟苯组(DNFB)、C组佛波酯组(TPA);1设为基质组,2设为保鲜膜组,3设为硅油组,分别计为A1、A2、A3;B1、B2、B3;C1、C2、C3。A1组(乙醇基质组)为单纯外搽90%乙醇,A2组(乙醇保鲜膜组)为外搽90%乙醇后加用保鲜膜覆盖,A3组(乙醇硅油组)为外搽90%乙醇后涂擦硅油; B1组(DNFB基质组)为单纯外搽0.5% DNFB,B2组为(DNFB保鲜膜组)为外搽0.5% DNFB后加用保鲜膜覆盖,B3组(DNFB硅油组)为外搽0.5% DNFB后涂擦硅油; C1组( TPA基质组)为单纯外搽0.01% TPA ,C2组(TPA保鲜膜组)为外搽0.01% TPA后加用保鲜膜覆盖,C(3TPA硅油组)为外搽0.01% TPA后涂擦硅油。各组经除毛后,第1天及第2天每日仅在B组的腹、背部涂擦1次,每次70微升,自第7天开始,每组均用相应的制剂治疗,每隔2日一次,每次70微升,加用保鲜膜组在涂相应制剂30分钟后于涂药区加盖保鲜膜,涂擦硅油组在涂相应制剂30分钟后于涂药区涂擦硅油,每日2次,造膜期为25天。实验结束后,于各组动物的腹、背部取小鼠皮肤活检,分别做普通病理(HE染色)及PCNA的免疫组化染色,在显微镜相同放大倍数下,测量各组表皮的厚度,计算均值;观察表皮细胞PCNA的染色,计数表皮PCNA阳性细胞数,计算PCNA阳性标记率,并计算均值,分别进行统计学分析。
结果:实验动物大体观察显示乙醇各组动物皮肤无潮红、增厚;DNFB各组动物皮肤轻度潮红、粗糙、增厚,个别部位稍有渗出、结痂,呈亚急性皮炎表现;TPA各组动物皮肤轻度潮红、表皮干燥、增厚,呈慢性皮炎表现。
组织病理显示乙醇各组未见表皮增厚,未见真皮内炎症细胞浸润,且各组PCNA阳性细胞表达仅限于基底细胞层;DNFB各组及TPA各组表皮明显增厚,真皮内较多量炎症细胞浸润,DNFB组及TPA组的PCNA阳性细胞表达分布于表皮的中下层包括基底细胞层和棘细胞层,其表达数量及表达厚度较乙醇各组均明显增加。DNFB基质组、TPA基质组分别比较乙醇基质组其表皮增生厚度及PCNA阳性标记率均在统计学上有显著性差异,P<0.05,亚急性皮炎、慢性皮炎表皮增生模型成功。DNFB保鲜膜组较DNFB基质组其表皮增生厚度及PCNA阳性标记率在统计学上未见显著性差异(P>0.05);DNFB硅油组较DNFB基质组其表皮增生厚度及PCNA阳性标记率在统计学上亦未见显著性差异(P>0.05)。
TPA保鲜膜组较TPA基质组其表皮增生厚度及PCNA阳性标记率在统计学上未见显著性差异(P>0.05);TPA硅油组较TPA基质组其表皮增生厚度及PCNA阳性标记率在统计学上亦未见显著性差异(P>0.05)。
结论:1.利用0.5%2,4二硝基氟苯(DNFB)及0.01%佛波酯(TPA)反复涂擦小鼠背部可以复制亚急性或慢性皮炎的模型。2.增生细胞核抗原在亚急性皮炎或慢性皮炎的动物模型中的表达明显增高。3.应用非通透性的膜覆盖及涂擦保湿剂硅油对亚急性及慢性皮炎小鼠模型的表皮增生没有明显的调节作用。
Objective: Epidermal barrier function would adjust the combination of keratinocyte DNA. In acute animal models, the combination of keratinocyte DNA will be increased while the epidermal barrier function degrades and the increasing extent is in direct retio with the degree of the normal barrier function. When the epidermal barrier function is improved, the combination of keratinocyte DNA will be restrained.The main feature of tissue pathology is epidermal over-proliferation and physiology chang is that epidermal barrier function degrades in the model of subacute and chronic dermatitis. At present , there is no study of relationships between epidermal barrier function and epidermal proliferation in model of subacute and chronic dermatitis. In the experiment, we eastablished models by application of 0.5%2,4-dinitro-1-flucrobenzene (DNFB) and 0.01% TPA on mouse backs. Epidermal barrier function was improved by covering with airtight memberance and repeated application of silicon oil on the models . Tissue pathology and expression of proliferation cell nuclear antigen [PCNA (pc10)] are used to assess whether epidermal proliferation was changed or not. Then we can draw a conclusion about whether epidermal barrier function is realated with epidermal proliferation in the model of subacute and chronic dermatitis.
Methods: The mouse were devided into there groups at random named with A,B,C .Every group was devided into subgroup named with 1,2,3. So we have 6 groups marked with A1,A2,A3;B1,B2,B3;C1,C2,C3. A-group is alcohol group. B-group is 0.5%2,4-dinito-1-flucrobene (DNFB) group. C-group is TPA group. Subgroup1 is control group. Subgroup2 is airtightmemberance group. Subgroup3 is silicon oil group. In the experiment, the application of 90% alcohol was only taken in A1 group mouse (alcohol-control group). The mouse were covered with airtight memberance after application of 90% alcohol in A2 group (alcohol- airtight memberance group). The mouse were applicated with silicon oil after 90% alcohol in A3 group (alcohol- silicon oil group). The application of 0.5% DNFB was only taken in B1 group mouse(DNFB -control group). The mouse were covered with airtight memberance after application of 0.5% DNFB in B2 group (DNFB - airtight memberance group). The mouse were applicated with silicon oil after 0.5% DNFB in B3 group (DNFB - silicon oil group). The application of 0.01% TPA was only taken in C1 group mouse (TPA -control group). The mouse were covered with airtight memberance after application of 0.01% TPA in C2 group (TPA - airtight memberance group). The mouse were applicated with silicon oil after 0.01% TPA in C3 group(TPA - silicon oil group). After the mouse fur were removed on the belly and back, Only B-group mouse were applicated with 70μl 0.5% DNFB once a day on the first and second day. From the seventh day, all groups were applicated with the right preperation 70μl once two days. In airtight memberance groups, the mouse skin was coverd with airtight memberance after the right preperation was applicated 30 minutes later. In silicon oil group, silicon oil was daubed on the skin after the right preperation was applicated 30 minutes later, twice aday. It took 25 days to mak ethe models. After the models were established, the tissue samples were taken and examined by pathology and immunnohistochemically stained examined with monodonal antibody [PCNA (pc10)] technique. The skin thickness of each sample was examined and the PCNA-positive cells were observed under the same multiple microscope. The average data was calculated and the statistic analysis was achieved.
Results: Tissue pathology shows that epidermal tickness did not changed and inflammation cells were not found in dermis. PCNA-positive cells were only expressed on stratum basalum in alcohol groups. Epidermal tickness increased obviously and there were more inflammation cells in dermis on the model of DNFB and TPA .PCNA-positive cells expressed not only on stratum basalum but also on the middle-low stratum spinosum inDNFB and TPA groups and PCNA-positive cells expressed more obviously. That means that epidermal tickness and the level of PCNA expression increased obviously in the model of DNFB and TPA groups than alcohol groups. There were remarkably statistical differences on epidermal tickness and the level of PCNA in the model of DNFB-control and TPA-control group compared with alcoho-control group (P<0.05). So the models of epidermal proliferation in subacute and chronic dermatitis were successed.
There were no statistical differences on epidermal tickness and the level of PCNA between the model of DNFB-airtight memberance and DNFB-control group(P>0.05). The same result came out between the model of TPA- airtight memberance and TPA-control group( P>0.05).There were no statistical differences on epidermic tickness and the level of PCNA between the model of silicon oil and control groups in DNFB and TPA (P>0.05).
Conclusion: 1. Repeated application of 0.5% DNFB and 0.01%TPA on the mouse back can make copies of the models of epidermal proliferation in subacute and chronic dermatitis. 2. The level of PCNA expression was increased obviously in the model of subacute and chronic dermatitis. 3. Covering with airtight memberance and application of silicon oil on mouse backs can not effectively adjust the epidermal proliferation in the model of subacute and chronic dermatitis.
引文
1. Proksch E, Feingold KR, Man MQ, et al. Barrier function regulates epidermal DNA synthesis[J]. J Clin Invest. 1991; 87(5):1668-73.
2. Matsumoto K, Mizukoshi K, Oyobikawa M, et al. Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments[J]. Skin Res Technol. 2004;10(2):122-9.
3. 杨军,Lee Seung Hun,黄晓波等.特应性皮炎炎动物模型表皮分化蛋白表达的改变.中国皮肤性病学杂志[J]. 2006,20(12): 730-733.
4. 苏顺清,辛时林,于冶.增殖细胞核抗原在增生性瘢痕组织中的表达与分布.中华整形外科杂志[J].2000,16(2):73-74.
5. Loden M, Maibach HI. Dry Skin and Moisturizers Chemistry and Function [M],Washington DC: CRC Press, 2000.
6. Sato J. Desquamation and the Role of Stratum Corneum Enzymes [M] // Leyden J, Rawlings A. Skin Moisturization. New York: Marcel Dekker Inc, 2002: 1-94.
7. Maas-Szabowski N, Starker A, Fusenig NE. Epidermal tissue regeneration and stromal interaction in HaCaT cells is initiated by TGF-alpha[J]. J Cell Sci. 2003;116(Pt 14):2937-48.
8. Sato N, Matsumoto H, Akimoto Y, et al. The effect of IL-1alpha and nifedipine on cell proliferation and DNA synthesis in cultured human gingival fibroblasts[J]. J Oral Sci. 2005;47(2):105-10.
9. Grossoni VC, Falbo KB, Kazanietz MG, et al. Protein kinase C delta enhances proliferation and survival of murine mammary cells[J].Mol Carcinog. 2007;46(5):381-390.
10. Xue M, Campbell D, Jackson CJ. Protein C is an autocrine growth factor for human skin keratinocytes[J]. J Biol Chem. 2007; 282:13610-13616.
11. Denda M, Wood LC, Emami S, et al. The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss[J].Arch Dermatol Res. 1996;288(5-6):230-8.
12. Demerjian M, Man MQ, Choi EH, et al. Topical treatment with thiazo lidinediones, activators of peroxisome proliferator-activated receptor -gamma, normalizesepidermal homeostasis in a murine hyper proliferative disease model[J]. Exp Dermatol. 2006;15(3):154-60.
13. Matsunaga Y, Ogura Y, Ehama R, et al. Establishment of a mouse skin model of the lichenification in human chronic eczematous dermatitis[J]. Br J Dermatol. 2007;156(5):884-91
14. Bourguignon LY, Ramez M, Gilad E, et al. Hyaluronan-CD44 interaction stimulates keratinocyte differentiation, lamellar body formation/secretion, and permeability barrier homeostasis[J].J Invest Dermatol. 2006; 126(6): 1356-65.
15. Kaya G, Tran C, Sorg O, et al. Hyaluronate Fragments Reverse Skin Atrophy by a CD44-Dependent Mechanism[J]. PLoS Med. 2006; 3(12): 2291-2302.
1. Loden M, Maibach HI. Dry Skin and Moisturizers Chemistry and Function [M],Washington DC: CRC Press, 2000.
2. Elias PM and Feingold KR.Lipid ang the epidermal water barrier: metabolism,regulation,andpathophysiology.SeminDermatal.1992;11(2):176-182.
3. Man MQ,Feingold KR,Elias PM.Exogenous lipids influence barrier recovery in acetone-treated murine skin.Arch Dermatol.19939,129(6):728-738.
4. Wang F, Man MQ,Elias P. A natura lipid mixture improves skin hydration in ichthyosis vulgaris. Int J Dermatol 1997;36:876-877.
5. Hara J,Higeuchi K,Okamoto R,et al.High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatol 2000;115:406-413.
6. Camlin SL,kao J,Frieden IJ,et al. Ceramide-dominant,barrierrepair lipids alleviate childhood atopic dermatitis:changes in barrier function provide asensitive indicator of disease activity. J Am Acad Dermatol.2002; 47(2):198-208.
7. 杨军,Lee Seung Hun,周立东等.特应性皮炎炎动物模型表皮脂合成的研究.中国麻风皮肤病杂志[J]. 2006,22(8): 649-651.
8. Man MQ,Feingold KR,Jain M,et al. Extracellular processing of phospholipids is required for permeability barrier homeostasis. J Lipid Res 1995; 36: 1925- 1935.
9. Holleran WM,Ginns E,Menon GK, et al. Consequences of? Glucocerebrosidase deficiency in epidermis :ultrastructure and permeability barrier alterations in Gaucher Disease. J Clin Invest 1994;93:1756-1764.
10. Jensen JM,Folster-Holst R,Baranowsky A,et al. Impaired sphingomyelinase activity and differentiation in atopic dermatitis. J Invest Dermatol 2004; 122: 1423-1431.
11. Wood L,Elias PM,Calhoun C,et al.Barrier disruption stimulates interleukin-1a expression and release from apre-fromed pool in murine epidermis.J Invest Dermatol 1996;106:397-403.
12. Wood L,Jackson SM,Elias PM,et,al.Cutaneous barrier perturbation stimulates cytokines production in the epidermis of mice.J Clin Invest 1992;90:482-487.
13. Proksch E,Feingold KR,Man MQ,et al.Barrier function regulates epidermal DNA synthesis.J Clin Invest 1991;87:1668-1673.
14. Grossman RM,Krueger J,Youish D,et al.Interleukin 6 is expressed in high level psoriatic skin and stimulates proliferation of cultured human keratinocytes.Proc Natl Acad Sci USA 1989;86:6367-6371.
15. Maas-Szabowski N, Starker A, Fusenig NE. Epidermal tissue regeneration and stromal interaction in HaCaT cells is initiated by TGF-alpha[J]. J Cell Sci. 2003;116(Pt 14):2937-48.
16. Sato N, Matsumoto H, Akimoto Y, et al. The effect of IL-1alpha and nifedipine on cell proliferation and DNA synthesis in cultured human gingival fibroblasts[J]. J Oral Sci. 2005;47(2):105-10.
17. Grossoni VC, Falbo KB, Kazanietz MG, et al. Protein kinase C delta enhances proliferation and survival of murine mammary cells[J].Mol Carcinog. 2007;46(5):381-390.
18. Xue M, Campbell D, Jackson CJ. Protein C is an autocrine growth factor for human skin keratinocytes[J]. J Biol Chem. 2007; 282:13610-13616.
19. Denda M, Wood LC, Emami S, et al. The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss[J].Arch Dermatol Res. 1996;288(5-6):230-8.
20. Demerjian M, Man MQ, Choi EH, et al. Topical treatment with thiazolidinediones, activators of peroxisome proliferator-activated receptor-gamma, normalizes epidermal homeostasis in a murine hyperproliferative disease model[J]. Exp Dermatol. 2006;15(3):154-60.
21. Matsunaga Y, Ogura Y, Ehama R, et al. Establishment of a mouse skin model of the lichenification in human chronic eczematous dermatitis[J]. Br J Dermatol. 2007;156(5):884-91
22. 杨军 ,Lee Seung Hun,黄晓波等 .特应性皮炎炎动物模型表皮分化蛋白表达的改变.中国皮肤性病学杂志[J]. 2006,20(12): 730-733.
23. Vahlquist A. Ichthyosis-an Inborn Dryness of the Skin[M]// Loden M, Maibach HI. Dry Skin and skin and Moisturizers; Chemistry and Function. Florida. CRC Press, 2000: 121-133.
24. Mavon A, Redoules D, Humbert P, et al. Changes in sebum levels and skin surface free energy components following skin surface washing[J]. Colloids and Surfaces B: Biointerfaces, 1998, 10 (3) 243-250.
25. Kobayashi H, Kikuchia K, Tsubono Y, et al. Measurement of elextrical current perception threshold of sensory nerves for pruritus in atopic dermatitis andnormal individuals with various degrees of mild damage to the stratum corneum [J]. Dermatology, 2003, 206(3): 204-211.
26. Denda M. Epidermal proliferative response induced by sodium dodecyl suplphate varies with environmental humidity[J]. Br J Dermatol , 2001, 145(2):252-257.
27. Okuda M, Yoshiike T , Ogawa H. Detergent-induced epidermal barrier dysfunction and is prevention[J]. J Dermatol Sci, 2002, 30(3): 173-179.
28. Fluhr JW, Mao-Qiang M, Brown BE, et al. Glycerol regulates stratum corneum hydration in sebaceous gland deficient (asebia) mice [J]. J Invest Dermatol, 2003, 120(5): 728-737.
29. Middleton JD. Development of a skin cream designed to reduce dry and flaky skin[J]. Soc Cosment Chem., 1974, 25(8): 519-534.
30. Katagiri C, Sato J, Nomura J, et L. Changes in environmental humidity affect the water-holding property of the stratum corneum and its free amino acid content, and the expression of filaggrin in the epidermis of hairless mice [J]. J Dermatol Sci, 2003, 31(1): 29-35.
31. Held E, Lund H, Agner T. Effect of different moisturizers on SLS-irritated human skin [J]. Contact Dermatitis, 2001, 44(4): 229-234.
2. Matsumoto K, Mizukoshi K, Oyobikawa M, et al. Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments[J]. Skin Res Technol. 2004;10(2):122-9.
3. 杨军,Lee Seung Hun,黄晓波等.特应性皮炎炎动物模型表皮分化蛋白表达的改变.中国皮肤性病学杂志[J]. 2006,20(12): 730-733.
4. 苏顺清,辛时林,于冶.增殖细胞核抗原在增生性瘢痕组织中的表达与分布.中华整形外科杂志[J].2000,16(2):73-74.
5. Loden M, Maibach HI. Dry Skin and Moisturizers Chemistry and Function [M],Washington DC: CRC Press, 2000.
6. Sato J. Desquamation and the Role of Stratum Corneum Enzymes [M] // Leyden J, Rawlings A. Skin Moisturization. New York: Marcel Dekker Inc, 2002: 1-94.
7. Maas-Szabowski N, Starker A, Fusenig NE. Epidermal tissue regeneration and stromal interaction in HaCaT cells is initiated by TGF-alpha[J]. J Cell Sci. 2003;116(Pt 14):2937-48.
8. Sato N, Matsumoto H, Akimoto Y, et al. The effect of IL-1alpha and nifedipine on cell proliferation and DNA synthesis in cultured human gingival fibroblasts[J]. J Oral Sci. 2005;47(2):105-10.
9. Grossoni VC, Falbo KB, Kazanietz MG, et al. Protein kinase C delta enhances proliferation and survival of murine mammary cells[J].Mol Carcinog. 2007;46(5):381-390.
10. Xue M, Campbell D, Jackson CJ. Protein C is an autocrine growth factor for human skin keratinocytes[J]. J Biol Chem. 2007; 282:13610-13616.
11. Denda M, Wood LC, Emami S, et al. The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss[J].Arch Dermatol Res. 1996;288(5-6):230-8.
12. Demerjian M, Man MQ, Choi EH, et al. Topical treatment with thiazo lidinediones, activators of peroxisome proliferator-activated receptor -gamma, normalizesepidermal homeostasis in a murine hyper proliferative disease model[J]. Exp Dermatol. 2006;15(3):154-60.
13. Matsunaga Y, Ogura Y, Ehama R, et al. Establishment of a mouse skin model of the lichenification in human chronic eczematous dermatitis[J]. Br J Dermatol. 2007;156(5):884-91
14. Bourguignon LY, Ramez M, Gilad E, et al. Hyaluronan-CD44 interaction stimulates keratinocyte differentiation, lamellar body formation/secretion, and permeability barrier homeostasis[J].J Invest Dermatol. 2006; 126(6): 1356-65.
15. Kaya G, Tran C, Sorg O, et al. Hyaluronate Fragments Reverse Skin Atrophy by a CD44-Dependent Mechanism[J]. PLoS Med. 2006; 3(12): 2291-2302.
1. Loden M, Maibach HI. Dry Skin and Moisturizers Chemistry and Function [M],Washington DC: CRC Press, 2000.
2. Elias PM and Feingold KR.Lipid ang the epidermal water barrier: metabolism,regulation,andpathophysiology.SeminDermatal.1992;11(2):176-182.
3. Man MQ,Feingold KR,Elias PM.Exogenous lipids influence barrier recovery in acetone-treated murine skin.Arch Dermatol.19939,129(6):728-738.
4. Wang F, Man MQ,Elias P. A natura lipid mixture improves skin hydration in ichthyosis vulgaris. Int J Dermatol 1997;36:876-877.
5. Hara J,Higeuchi K,Okamoto R,et al.High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatol 2000;115:406-413.
6. Camlin SL,kao J,Frieden IJ,et al. Ceramide-dominant,barrierrepair lipids alleviate childhood atopic dermatitis:changes in barrier function provide asensitive indicator of disease activity. J Am Acad Dermatol.2002; 47(2):198-208.
7. 杨军,Lee Seung Hun,周立东等.特应性皮炎炎动物模型表皮脂合成的研究.中国麻风皮肤病杂志[J]. 2006,22(8): 649-651.
8. Man MQ,Feingold KR,Jain M,et al. Extracellular processing of phospholipids is required for permeability barrier homeostasis. J Lipid Res 1995; 36: 1925- 1935.
9. Holleran WM,Ginns E,Menon GK, et al. Consequences of? Glucocerebrosidase deficiency in epidermis :ultrastructure and permeability barrier alterations in Gaucher Disease. J Clin Invest 1994;93:1756-1764.
10. Jensen JM,Folster-Holst R,Baranowsky A,et al. Impaired sphingomyelinase activity and differentiation in atopic dermatitis. J Invest Dermatol 2004; 122: 1423-1431.
11. Wood L,Elias PM,Calhoun C,et al.Barrier disruption stimulates interleukin-1a expression and release from apre-fromed pool in murine epidermis.J Invest Dermatol 1996;106:397-403.
12. Wood L,Jackson SM,Elias PM,et,al.Cutaneous barrier perturbation stimulates cytokines production in the epidermis of mice.J Clin Invest 1992;90:482-487.
13. Proksch E,Feingold KR,Man MQ,et al.Barrier function regulates epidermal DNA synthesis.J Clin Invest 1991;87:1668-1673.
14. Grossman RM,Krueger J,Youish D,et al.Interleukin 6 is expressed in high level psoriatic skin and stimulates proliferation of cultured human keratinocytes.Proc Natl Acad Sci USA 1989;86:6367-6371.
15. Maas-Szabowski N, Starker A, Fusenig NE. Epidermal tissue regeneration and stromal interaction in HaCaT cells is initiated by TGF-alpha[J]. J Cell Sci. 2003;116(Pt 14):2937-48.
16. Sato N, Matsumoto H, Akimoto Y, et al. The effect of IL-1alpha and nifedipine on cell proliferation and DNA synthesis in cultured human gingival fibroblasts[J]. J Oral Sci. 2005;47(2):105-10.
17. Grossoni VC, Falbo KB, Kazanietz MG, et al. Protein kinase C delta enhances proliferation and survival of murine mammary cells[J].Mol Carcinog. 2007;46(5):381-390.
18. Xue M, Campbell D, Jackson CJ. Protein C is an autocrine growth factor for human skin keratinocytes[J]. J Biol Chem. 2007; 282:13610-13616.
19. Denda M, Wood LC, Emami S, et al. The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss[J].Arch Dermatol Res. 1996;288(5-6):230-8.
20. Demerjian M, Man MQ, Choi EH, et al. Topical treatment with thiazolidinediones, activators of peroxisome proliferator-activated receptor-gamma, normalizes epidermal homeostasis in a murine hyperproliferative disease model[J]. Exp Dermatol. 2006;15(3):154-60.
21. Matsunaga Y, Ogura Y, Ehama R, et al. Establishment of a mouse skin model of the lichenification in human chronic eczematous dermatitis[J]. Br J Dermatol. 2007;156(5):884-91
22. 杨军 ,Lee Seung Hun,黄晓波等 .特应性皮炎炎动物模型表皮分化蛋白表达的改变.中国皮肤性病学杂志[J]. 2006,20(12): 730-733.
23. Vahlquist A. Ichthyosis-an Inborn Dryness of the Skin[M]// Loden M, Maibach HI. Dry Skin and skin and Moisturizers; Chemistry and Function. Florida. CRC Press, 2000: 121-133.
24. Mavon A, Redoules D, Humbert P, et al. Changes in sebum levels and skin surface free energy components following skin surface washing[J]. Colloids and Surfaces B: Biointerfaces, 1998, 10 (3) 243-250.
25. Kobayashi H, Kikuchia K, Tsubono Y, et al. Measurement of elextrical current perception threshold of sensory nerves for pruritus in atopic dermatitis andnormal individuals with various degrees of mild damage to the stratum corneum [J]. Dermatology, 2003, 206(3): 204-211.
26. Denda M. Epidermal proliferative response induced by sodium dodecyl suplphate varies with environmental humidity[J]. Br J Dermatol , 2001, 145(2):252-257.
27. Okuda M, Yoshiike T , Ogawa H. Detergent-induced epidermal barrier dysfunction and is prevention[J]. J Dermatol Sci, 2002, 30(3): 173-179.
28. Fluhr JW, Mao-Qiang M, Brown BE, et al. Glycerol regulates stratum corneum hydration in sebaceous gland deficient (asebia) mice [J]. J Invest Dermatol, 2003, 120(5): 728-737.
29. Middleton JD. Development of a skin cream designed to reduce dry and flaky skin[J]. Soc Cosment Chem., 1974, 25(8): 519-534.
30. Katagiri C, Sato J, Nomura J, et L. Changes in environmental humidity affect the water-holding property of the stratum corneum and its free amino acid content, and the expression of filaggrin in the epidermis of hairless mice [J]. J Dermatol Sci, 2003, 31(1): 29-35.
31. Held E, Lund H, Agner T. Effect of different moisturizers on SLS-irritated human skin [J]. Contact Dermatitis, 2001, 44(4): 229-234.