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.8-mop/uva Human Skin Photoaging Formation And Aryl Vitamin A Acid Ethyl Ester Antagonism

Posted on:2002-05-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z R LiuFull Text:PDF
GTID:1114360032455203Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
There was absent of a reliable and practical human model for research of human skin photoaging yet.Clinically, appearance of premature aging of the skin is prominent side effect photochemotherapy with psoralnes and ultraviolet A (PUVA) in dermatology.It is possible that the synergistic actions of 8-MOP/UVA would provide models in vivo and in vitro for studies of skin photoaging.However,the molecular mechanisms underlying premature aging up 8-MOP/UVA are as yet unknown.In our studies, dermis of the non-lesion back skin of vulgar psoriatic patients who had been treated by PUVA and the cultured foetus dermic fibroblasts were selected to be observed.The techniques and methods,HE stain,Verhoeff stain,electron microscope, enzyme cytochemistry, immunocytochemistry (ICC), in situ hybridization histochemistry (ISHH),flow cytometer (FCM), three primers PCR,PCR-SSCP and direct sequencing of PCR products ,were used to study influences of 8- MOP/U VA on formation of skin photoaging and arotiniod ethylster antagonism,the skin photoaging-characteristic biological markers inc1ude:~ID histopathology of skin dermis; ?expression of SA- P -galactosidase; ? expression of p16 protein;~43expression of mRNA of two MMPs, interstitial collagenase(MMP-1),stromelysin-1(MMP-3) and the protein of their inhibitor TIMP-1;゛ccumulations of mutations of mtDNA.The resluts were as follows: 1 .By the cooperation of 8-MOPIUVA , the degenerated collagen and elastic fibers were increasing,curling and ranking derangement in dermis of the III ? non-lesion back skin of vulgar psoriatic patients. 2.By the cooperation of 8-MOPIUVA ,tbe photoaging-characteristic biological markers of the dermic fibroblasts in vivo and in intro were changed as follows: 0 with a permanent switch of mitotic to stably postmitotic phentypes, fibroblasts displayed growth suppression and morphological changes of cell senescence;﹊ncreasing expression of SA- P -galactosidase; 甶ncreasing expression of p16 protein;Ocontinuous up-regulation of mRNA of MMP- 1 and MMP-3 ,while the protein of TIMP- 1 was only slightly induced; ~high levels of the 4977bp deleted mtDNA accumulated in dermis and cultured fibroblasts,and large accumulation of a A~* C base transversion of 414 position of DLP6 of human mtDNA control region for replication of cultured fibroblasts also. 3 .Arotiniod ethylester could antagonize the photoaging-characteristic changes of dermis of the skin and cultured fibroblasts that induced by 8- MOP/U VA. Conclusions: 1 .The cooperation of 8-MOP/UVA could induced dermis of the non- lesion back skin of vulgar psoriatic patients and the cultured dermic fibroblasts showed up photoaging-cbaracteristic changes of histology and biology rapidly,it is feasible to establish human skin photoaging models by selected the human skin of sun-protected sites treatment with PUVA and cultured dermic fibroblasts treatment with 8-MOPIUVA as studied objects. 2.The cooperation of 8-MOP/UVA could induced dermis of the non- lesion back skin of vulgar psoriatic patients and the cultured dermic fibroblasts produced large aging-associated mutations of mtDNA rapidly,it is feasible to establish human models in vivo and in vitro which could produced large TV...
Keywords/Search Tags:skin, photoaging, fibroblast, senescence, mitochondrial DNA, mutation, model, arotiniod ethylster, antagonism
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