Font Size: a A A

The Effect And Mechanism Of MCEO In Regulating Psoriasis-like Inflammatory Skin Injury In Mice Through PI3K/mTOR And P38 MAPK Signaling Pathways

Posted on:2024-07-04Degree:MasterType:Thesis
Country:ChinaCandidate:G Y LiaoFull Text:PDF
GTID:2544307166968619Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
Psoriasis is a complex chronic inflammatory skin disease with strong genetic susceptibility and autoimmune pathogenic characteristics,which has a greater impact on the life of patients.Traditional treatment is difficult to adhere to for a long time due to large side effects,resulting in the patient’s condition being prone to relapse.Due to the increased frequency of clinical use of monoclonal antibody biologics targeting cytokines,the prolongation of patients’ medication time,and other problems such as reduced efficacy of biological agents and frequent adverse reactions have occurred.To this end,we take traditional medicine as the starting point to screen plant drugs with high efficiency,low toxicity and anti-psoriasis effect from natural plants,which is a practical and effective way to solve the problem of clinical psoriasis treatment.Matricaria chamomilla essential oil(MCEO)is a plant extract with proven anti-inflammatory,antibacterial and anticancer properties,and its anti-inflammatory effect in human keratinocytes(Ha Ca T cells)has been reported,but the efficacy and mechanism of action of MCEO in animal models have not been reported.In this paper,the clinical effect of external MCEO on psoriasis-like inflammatory skin injury induced by imiquimod(IMQ)was studied,and the exact mechanism of action of MCEO was explored by molecular biology technology,aiming to provide the necessary theoretical and experimental basis for the clinical application of MCEO.In this experiment,we first used olive oil to dilute the MCEO stock solution(MCEO stock solution concentration of 800mg/m L)10 times and mix it well.Animal grouping and treatment: 28 female BALB/c mice weighing about 20 g at 8-9 weeks were randomly divided into three groups:group A(normal control group),group B(IMQ model group),and group C(MCEO pretreatment group).After grouping,the mice were given dorsal hair removal with a hair removal area of about 2.5 cm × 3 cm.Group A:Olive oil was used to coat the hair removal parts of mice at 7 a.m.and 7p.m.daily;Group B: Apply IMQ cream at 12 noon every day,62.5mg/each time,to construct a psoriasis-like inflammatory skin disease model;Group C: After seven days of MCEO pretreatment,IMQ+MCEO was continuously treated for 7 days.Apply to the back daily at 7 a.m.and 7 p.m.with 10 times diluted in olive oil for seven days.Subsequently,while treating mice with MCEO in the morning and evening,IMQ cream was applied at 12 noon,and then applied continuously for 7 days;The state of each group of mice was observed every day,photographed and recorded,and three people scored according to the Psoriasis Area and Severity Index(PASI)scoring standard,and the mice were sacrificed on day 8,and the peripheral blood and back skin tissue of mice were collected for follow-up experiments.Clinical efficacy of MCEO on IMQ-induced psoriasis-like dermatitis in mice: The results of HE staining showed that compared with group A,group B mice had significantly thicker spine layer(P<0.0001),more inflammatory cell infiltration was seen in the superficial dermis,and the PASI score was also significantly higher than that of group A(P<0.0001);compared with group B,group C mice had significantly thinner skin spine layer(P<0.001),significantly shorter superficial epidermal protrusion,and only a small amount of inflammatory cell infiltration was seen in the superficial dermis.The difference was statistically significant.The mechanism of action of MCEO in regulating IMQ-induced psoriasis-like dermatitis in mice: the expression level of related inflammatory cytokines in each group of mice was enhanced by q RT-PCR and Luminex using mouse skin tissue.Western Blot and IHC detect changes in expression levels of PI3K/mTOR and P38 MAPK signaling pathway proteins.q RT-PCR,Luminex and Western Blot results showed that the expression levels of IL-6 and IL-1β m RNA in group B were significantly increased(P<0.05,P<0.01)compared with group A,and the expression levels of inflammatory cytokines such as IL-1β,TNF-α,IFN-γ,IL-10 and IL-17 A were significantly increased in the peripheral serum of mice in group B(P<0.01),p-P38 MAPK,The expression levels of p-PI3 K and p-mTOR proteins were significantly increased(P<0.001,P<0.001,P<0.05),and compared with Group B,Group C significantly downregulated the expression of IMQ-induced inflammatory cytokines IL-1β and IL-6 m RNA(P<0.05,P<0.01),and also significantly reduced the levels of IL-1β,TNF-α,IFN-γ(P<0.05)and p-P38 MAPK,p-PI3 K,PmTOR protein expression levels(P<0.01,P<0.01,P<0.001).The results of IHC staining showed that compared with group A,the expression of P38 and PI3K in group B increased significantly,while the expression levels of P38 and PI3 K proteins in group C were significantly lower than those in group B after MCEO pretreatment,which proved that MCEO can regulate inflammatory skin injury by inhibiting the activation of P38 MAPK and PI3K/mTOR signaling pathways.In summary,MCEO can regulate the expression levels of inflammatory cytokines such as IL-6 and IL-1β associated with psoriasis by regulating the activity of P38 MAPK and PI3K/AKT/mTOR signaling pathways,thereby playing a preventive and therapeutic role in the prevention and treatment of inflammatory skin diseases.The next step will be to analyze the active ingredients in MCEO,screen the main functional ingredients for animal validation experiments,and provide more specific experimental data for clinical application.
Keywords/Search Tags:Matricaria chamomilla essential oil(MCEO), Psoriasis, Imiquimod cream(IMQ), Psoriatic inflammatory dermatosis, Mitogen-activated protein kinase P38(P38 MAPK), Phosphatidylinositol-3 kinase(PI3K), Mammalian rapamycin target protein(mTOR)
PDF Full Text Request
Related items