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Experimental Study Of Effects Of The Ointment Of FGF10Monoc-Lonal Antibody On A Mouse Model Of Psoriasis

Posted on:2013-12-04Degree:MasterType:Thesis
Country:ChinaCandidate:J Y WangFull Text:PDF
GTID:2234330371483222Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Background:Psoriasis is commonly called oxhide lichen,which is a chronic,inflammatory and i-mmune abnormal disease of the skin. The cause of the disease is complicated. It can be knowas a disease which is mediated mainly by T cells,the immune function of human body isabnormal and normal cells are attacked,in which many kinds of cytokines participate. Thecytokines,which T cells, macrophages and other cells secrete,can regulate new inflammatorycells moved into the skin, increasing the activity of T cells, eventually leading to excessiveproliferation of keratinocyte.Its clinical manifestations of the erythema,the silver scalescovering, the reddish film and the punctate bleeding (Auspitz’s sign)are characteristic. Thehistopathologic features of psoriasis show that hyperkeratinization, parakeratosis,trochanterellus extension,stratum granulosum deficiency, inflammatory cell infiltration andtelangiectasis in dermis.Fibroblast growth factor-10(FGF10) is a member of the family of FGFs. Studies on itsbiological function show that FGF10may not only promotes the growth and proliferation ofkeratinocytes, but also affects on cell migration. In vitro, experimental studies have shownthat FGF10monoclonal antibody has negative growth effects on cultured keratinocyte cells(wait for publication).Whether FGF10monoclonal antibody has inhibitory effect onproliferation of cells of animal model of psoriasis, there is no report on which domestic andabroad. FGF10monoclonal antibody as a new development of biological agents, whether itcan affect on psoriasis treatment, should confirmed by further studies like animalexperiments and clinical trials.Psoriasis is a refractory dermatosis, and now many scholars domestic and abroaddedicate themselves to the biological treatment of psoriasis, and confirm the efficacy andsafety of biological agents. The biological treatment has its own advantages, such as targeted,effective, and less adverse reactions. The biological treatment is a new method and a newway for psoriasis,which will bring new hope for the majority of patients with psoriasis.Objective:To investigate whether the ointment of FGF10monoclonal antibody can inhibit proliferation of cells in animal model of psoriasis;To understand the biological significanceof FGF10monoclonal antibody and fibroblast growth factor family;And to provide atheoretical basis on biological treatment of psoriasis.Methods:FGF10monoclonal antibody(3.76mg/ml)was diluted into three groups:20times(0.188mg/ml),40times (0.094mg/ml),and60times (0.063mg/ml), and made them intoointment respectively.We selected the female mice as the object of study for animal model ofpsoriasis.Thirteen mice were randomly selected into the blank group and others weremodeled.After mice were successfully modeled, they were randomly divided into fivegroups: light concentration of FGF10monoclonal antibody group, medial concentration ofFGF10monoclonal antibody group, high concentration of FGF10monoclonal antibodygroup, positive control group (ointment of Hydrocortisone Butyrate group) and modelcontrol group. By vaginal-administration drugs, after3days,executed the mice and got thevaginal tissues. Then they were fixed in formalin, embedded in paraffin, and stained with HEstaining. In the light microscope, counted mitotic divisions of300basal cells of mice vaginalepithelial cells., they would translated into number of100basal cell mitosis, that is mitoticindex. To compared the mitotic index of basal cells of mice vaginal epithelial cells, the singlefactor analysis of variance (One-way ANOVA) was used to analyse the data of thegroups.The changes and differences of the different groups of vaginal epithelial cells withLight microscope were observed.Results:1. Analyzed by statistical software(SPSS13.0): Results of Homogeneity of variance testshowed that the samples were homogeneous.Method of LSD was used to compare the meanof the blank group,positive control group,high concentration of FGF10monoclonalantibody group, medial concentration of FGF10monoclonal antibody group and the lightconcentration of FGF10monoclonal antibody group respectively with the model group, Theresults of these comparison were p=0.000,0.037,0.001,0.001,0.031,p <0.05, The statisticmeaning of the difference between the two groups was significant, and the difference waspositive.The analysis between the groups of the light concentration of FGF10monoclonalantibody group, medial concentration of FGF10monoclonal antibody group, highconcentration of FGF10monoclonal antibody group,and positive control group showed p>0.05, The statistic meaning of the difference between the two groups was nonsignificant.2. Mice vaginal opening manifested as model group was more humid,swell than the blank group,and secreted discharge occasionally. The light microscopy reflected that,inmodel group, the vaginal tissue lined by the well-differentiated squamous epithelial, manymitotic phase cells can be seen in the basal layer; the positive control group and the threegroups of FGF10monoclonal antibody also covered with well-differentiated squamousepithelial, but a few mitotic phase cells can be seen in the basal layer.Conclusions:1. In this study, the animal model of psoriasis induced by estrogen,which showedparaplastic of vaginal epithelial cells, has successfully modeled;2. The study showed that FGF10monoclonal antibody has inhibited mitotic divisionof basal cells of mice vaginal epithelial cells. It could be inferred that FGF10monoclonalantibody has inhibitory effect on animal model of psoriasis,and it could be used as atreatment of psoriasis, provided a new idea for biologic therapy of psoriasis;3. The light concentration of FGF10monoclonal antibody group, medial concentrationof FGF10monoclonal antibody group, high concentration of FGF10monoclonal antibodygroup, and positive control group had no significant difference between each other by thecomparison of the mitotic index of basal cells of mice vaginal epithelial cells.The fourgroups were of equivalent efficacy, we could not infer which group has better effect.
Keywords/Search Tags:Therapy for psoriasis, FGF10monoclonal antibody, Animal models of psoriasis
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