Study On The Treatment Of Intense Pulsed Light Combined With Glycolic Acid On Photoaging And The Role Of CD26 In Photoaging

Background:Photoaging is the phenomenon of premature skin aging caused by ultraviolet rays acting on the skin for a long time.The action of ultraviolet rays on the skin causes the increase of reactive oxygen species(ROS),activates the surface receptors of cells and recruits downstream mitogen-activated protein kinase(MAPK)to cause the activation of AP-1,which leads to the increase of matrix metalloproteinase(MMP),degrading collagen fibers.Ultraviolet rays can also inhibit the TGF-βpathway,reduce the synthesis of Smad-2 3 and Smad-4 complexes,inhibit collagen hyperplasia,and promote the progress of photoaging.Photoaging is clinically manifested as wrinkles,telangiectasia,Abnormal pigmentation,dry skin,decreased elasticity,some accompanied by precancerous lesions.Bibliometrics is the use of mathematical or statistical methods to analyze literature data in a certain field to track research hotspots and prefaces in this field.The treatment of photoaging includes drugs and photoelectric therapy,glycolic acid skin peeling and intense pulsed light is an important means to treat photoaging.Glycolic acid promotes the renewal of epidermis,and intense pulsed light acts on the dermis to promote collagen synthesis to achieve the purpose of improving photoaging.CD26-positive fibroblasts can be used as a special subpopulation that can participate in collagen synthesis through the Smad pathway,but whether CD26 is involved in the photoaging process has not yet been studied.Objective:The knowledge structure and research hotspots of photoaging were summarized through Bibliometric analysis,and the effectiveness and safety of glycolic acid combined with intense pulse light in the treatment of facial photoaging were explored,and whether CD26 molecules participated in the photoaging process were studied,which provided a new perspective for the mechanism research and treatment of photoaging.Methods:1.Screening the studies related to photoaging in Pub Med and Wo SCC databases,and according to the characteristics of semantics,the corresponding algorithm analysis is carried out on the major Me SH headings/subheadings and keywords of the studies,and the knowledge structure and research hotspots of photoaging are obtained respectively.2.We recruited photoaging subjects clinically,taking intense pulse light combined with glycolic acid therapy as the experimental group,intense pulsed light alone treatment as the control group,the method of split-face randomized controlled trial is choose,after half-year treatment,compared the safety and efficacy of combination therapy and single treatment,and the photoaging model of mice was used to evaluate the histological changes of the intense pulsed light alone treatment group,the glycolic acid alone treatment group and the intense pulsed light combined with glycolic acid treatment group,as well as the CD26 molecules expression level after intense pulsed light therapy.3.Construction of photoaging models for single UVA and repeated UVA exposures,and the effect of the model construction was verified by detecting MMP3 and COL I.Long-wave ultraviolet(UVA)irradiation fibroblasts at different doses(0,5,10,15J/cm~2)to observe the expression of CD26 molecules.The expression of CD26 was observed after15J/cm~2 UVA single irradiating at 8h,12h,24h,36h.Lentivirus to used to establish a fibroblast model with low expression of CD26 molecules,In animal experiments and cell experiments,the expression changes of CD26in chronic photoaging models were further verified.Fibroblasts were transfected with lentivirus to knock down CD26,and the knockdown efficiency was verified at the m RNA level and protein level.Observe the effect of knocking down CD26 on the changes of senescence phenotype indexβ-galactosidase and damage phenotype indexγH2AX and verify whether CD26 has a protective effect on photodamage through Nrf2.In the photoaging model of single UVA exposure and repeated UVA exposure,respectively,detecting the effect of low expression of CD26 on type I collagen fibers and MMP3 at the protein level,in the end,the Smad and MAPK signaling pathways and Nrf2 changes in low-expression CD26 cells were observed.Results:1.The knowledge structure of photoaging includes the pathophysiology,prevention,and treatment of photoaging;treatment methods such as carbon dioxide laser,intense pulsed light,and glycolic acid are research hotspots in photoaging treatment;the research hotspots of photoaging in the past five years are:Mitogen-activated protein kinase(MAPK),Nrf2 and antioxidant activity.2.The subjects had no obvious side effects on the combined treatment group and the single treatment group,and the treatment with intense pulsed light combined with glycolic acid once took effect.Intense pulsed light therapy alone was effective for 3 sessions.Half a year later,there was no significant difference in the curative effect between the combined group and the single group.In the mouse model,the collagen fibers in the combined treatment group,intense pulsed light and glycolic acid alone treatment group were densely arranged,and the immunohistochemical staining of type I collagen fibers in the combined treatment group and the intense pulsed light alone treatment group was more obvious,the expression of CD26 in mouse tissues after intense pulsed treatment was increased.3.The expression of CD26 in fibroblasts was dose-and time-dependent with UVA.After knockdown of CD26 in single UVA irradiation,the staining ofβ-galactosidase was aggravated and the staining ofγH2AX was increased,and the expression of Nrf2 was downregulated after both single and repeated UVA irradiation.After single and repeated UVA irradiation,the content of type I collagen fibers in the low expression group showed a downward trend.After single and repeated UVA irradiation,the phosphorylation level of Smad2/3 in the low expression group was significantly lower than that in the control group.After a single UVA irradiation,the MMP3 protein level in the low expression group was significantly higher than that in the control group.After multiple UVA irradiation the level of MMP3 protein in the low expression group was significantly lower than that in the control group.After a single UVA irradiation,the phosphorylation level of MAPK protein in the low expression group was higher than that in the control group,and after repeated UVA,the phosphorylation level of MAPK protein in the low expression group was lower than that in the control group.Conclusion:1.Glycolic acid and intense pulsed light are important means to treat photoaging.The characteristic molecules of recent photoaging research are MAPK and Nrf2.2.Intense pulsed light combined with glycolic acid is safe and effective in the treatment of photoaging,and the combination group is more effective than that alone.The group takes effect quickly.In the mouse model,the hyperplasia of collagen fibers in the dermis of the intense pulsed light combined treatment group and the single treatment group was obvious,and the expression of CD26 in the two groups was increased.3.CD26 molecules are reactive to UVA,CD26 expression is increased in photoaging cells after single and repeated UVA irradiation,and CD26 has a protective effect on photoaging.CD26 protects against photoaging through Nrf2 after single and repeated UVA exposure.After a single UVA exposure,CD26 protects against photoaging through the Smad pathway and the MAPK pathway.After repeated UVA irradiation,CD26 protects photoaging through the Smad pathway,and the effect on MAPK is not consistent with single irradiation.