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Effects Of Slit2 On Inflammatory Infiltration And Angiogenesis In Mouse Model Of Imiquimod-Induced Psoriasis

Posted on:2024-08-24Degree:MasterType:Thesis
Country:ChinaCandidate:L XiongFull Text:PDF
GTID:2544307175476984Subject:Dermatology and venereology
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BackgroundPsoriasis is a common chronic,autoimmune,inflammatory disease;and mainly characterized by erythema,scaly plaques with pathological features of epidermal keratinocyte proliferation,dermal inflammatory cell infiltration and neovascularization.The pathogenesis of psoriasis is complex and has not been fully elucidated.At present,many studies have shown that the onset and progression of psoriasis are initiated and maintained by the interaction between innate and acquired immune cells,among which dendritic cells,T lymphocytes and keratinocytes are dominant,and IL-23/Th17 axis is regarded as the main pathogenesis.A number of studies have confirmed that Slit2 and its related pathways are involved in immune cell infiltration,leukocyte chemotaxis,angiogenesis,endothelial cell migration and vascular leakage.Many studies have shown that Slit2 plays a role in regulating inflammatory infiltration and angiogenesis.Psoriasis is a chronic inflammatory disease,and inflammatory infiltration and angiogenesis are significant features of psoriasis.However,no study has shown that Slit2 and its related pathways play roles in psoriasis.The purpose of this study is to investigate the effect of Slit2 on inflammatory infiltration and angiogenesis in imiquimod-induced psoriasis-like dermatitis in mice,and supplement the relevant pathogenesis of psoriasis.ObjectiveThe aim of this study is to investigate the effect of Slit2 on inflammatory infiltration in mouse psoriasiform dermatitis model,and angiogenesis in mouse sponge model.Methods1.The expression of Slit2 in mice with imiquimod-induced psoriasis-like lesions was detected by immunofluorescence.PCR and Western blot were employed to detect the expression level of Slit2 in mouse psoriasis-like lesions.2.Establish an imiquimod-induced psoriasis-like dermatitis mouse model.C57BL/6 mice were divided into 5 groups randomly: control group,IMQ model group,Slit2 si RNA group,Slit2 protein low-dose group(100 ng/m L)and high-dose group(300ng/m L).The severity of back lesions of mice was evaluated by PASI score every day.The Histopathological changes of mouse skin lesions were observed by HE staining;The m RNA expression levels of IL-23,IL-22 and IL-17 A were measured using RT-PCR;Immunohistochemistry was used to detect the expression of ki67 in epidermis and the number of CD3+T cells.3.Establish an imiquimod-induced psoriasis-like dermatitis mouse Sponge model.C57BL/6 mice were divided into 4 groups random Ly: control group,IMQ model group,IMQ+Slit2 si RNA group,and IMQ + Slit2 protein group.Angiogenesis was observed by HE staining;the expression of CD31 was detected by Immunofluorescence;and the infiltration of CD3+T cells,CD11c+ Dendritic cells and IL-17A+ cells in the sponge was measured by immunohistochemistry.Results1.Slit2 was expressed in both epidermis and dermis of psoriasis-like lesions,but mainly in epidermis,and the expression of Slit2 was increased in the psoriasis-like skin lesions induced by imiquimod in mice.2.In the mouse model of psoriasiform dermatitis,after treatment with Slit2 si RNA,PASI score,epidermal thickness,inflammatory cells infiltration and vessel density in dermis,the degree of epidermal proliferation,the number of CD3+T cells and the expression of IL-23,IL-22 and IL-17 A m RNA levels were increased compared with the IMQ group.While compared with IMQ group,the Slit2 protein treatment group demonstrated great alleviation in the symptoms mentioned above.3.In the mouse Sponge model,Slit2 si RNA treatment significantly increased the number of blood vessels,the expression of CD31,the infiltration of CD3+ T cells,CD11c+ Dendritic cells and IL17A+ cells compared with the IMQ group.However,the Slit2 protein treatment reduced the number of blood vessels,the expression of CD31,the infiltration of CD3+ T cells,CD11c+ Dendritic cells and IL17A+ cells compared with the IMQ group.Conclusion1.Slit2 was expressed in both epidermis and dermis of psoriasis-like lesions,but mainly in epidermis,and the expression of Slit2 was increased in the psoriasis-like skin lesions induced by imiquimod in mice.2.Compared with the IMQ group,silence the expression of Slit2 in psoriasis-like lesions can aggravate the severity of Psoriasis and increased inflammation cells infiltration,treatment with recombinant Slit2 protein can alleviate psoriasis-like lesions and decrease inflammation cells infiltration.Therefore,Slit2 has certain anti-inflammatory effects in imiquimod-induced psoriasis-like dermatitis mouse model.3.Inhibition of Slit2 expression by Slit2 si RNA increased angiogenesis,while treatment with recombinant Slit2 protein inhibited angiogenesis.Thus,Slit2 has an anti-angiogenic effect in imiquimod-induced psoriasis-like dermatitis mouse model.
Keywords/Search Tags:Slit2 protein, Slit2 siRNA, psoriasis, imiquimod, Inflammatory infiltration, Angiogenesis
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