| Objective:(I)To observe the effect of abnormal lipid metabolism on psoriasis by using the mouse model induced by Imiquimod(IMQ)cream based on apolipo E gene knockout(Apo E KO)to explore the role of abnormal lipid metabolism in psoriasis and provide a theoretical basis for the study of pathogenesis of psoriasis.(II)To explore the expression and significance of FLG,CARD14 and TNIP1 in skin lesions of psoriasis vulgaris and generalized pustular psoriasis.Methods:Part I: Effect of Abnormal Lipid Metabolism on Imiquimod-Induced Psoriasis Mouse ModelTwelve healthy 6-to 8-week-old male C57BL/6 mice and Apo E KO mice(C57BL/6 background)were fed with the same high-fat diet for 16 weeks.The mice were randomly divided into 4 groups according to gene types and treatment conditions.Including(1)wild type(Wild-type,WT)control group,(2)Apo E KO control group,(3)imiquimod(IMQ)induced WT model group,(4)IMQ induced Apo E KO model group.In the IMQ-induced psoriasis model group,5% imiquimod cream was applied to the back of mice every day,and in the control group,the same part of mice was applied vaseline for control for 10 days.Serum lipids of mice were detected by ELISA,including total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),visfatin and Chemerin,and inflammatory factors were detected by inflammatory antibody microarray.Part II: Expression of FLG,CARD14 and TNIP1 in psoriatic lesionsParaffin tissue samples of 32 patients with psoriasis vulgaris(Ps V)and 23 patients with generalized pustular psoriasis(GPP)from January 2013 to January 2019 were collected from the Department of Dermatology of the Affiliated Hospital of Inner Mongolia Medical University,and 32 normal skin paraffin tissue specimens were selected as control.Paraffin tissue samples were stained by immunohistochemistry.Image-pro plus 6.0 software(Media Cybernetics,Inc.,Rockville,MD,USA)was used to calculate the IOD value and the ratio of positive cells in the stained pictures.The expression of protein in FLG,CARD14 and TNIP1 in each group were observed and compared,and the correlation of each gene in psoriasis skin lesions was examined.Results:Part I: Effect of Abnormal Lipid Metabolism on Imiquimod-Induced Psoriasis Mouse Model(1)Skin lesions and PASI scores of mice: IMQ-induced skin thickening,erythema and scale appeared in Apo E KO and WT psoriasis mice,and Apo E KO mice showed stronger skin lesions and higher PASI scores than WT mice.During the experimental period,there was no visible inflammatory change in the back skin of the control mice,and their PASI scores tended to be 0.(2)Histopathological analysis: HE staining slices of IMQ-induced Apo E KO and WT mice with psoriasis showed epidermal thickening,hyperkeratosis,keratosis insufficiency,keratinocyte aggregation,hypertrophic spines with epidermal protrusion,and superficial dermis with capillary hyperplasia and lymphocytic infiltration.(3)The serum levels of TC,TG,LDL in Apo E KO model group were significantly higher than those in WT model group,and the levels of HDL were significantly lower than those in WT model group(P < 0.05).(4)The levels of serum Visfatin and Chemerin in Apo E KO model group were significantly higher than those in WT model group(P< 0.05).(5)The expression of IL-1α、IL-1β、IL-6、IL-17、IL-12 p40/p70、TNFα、IFNγ in Apo E KO model group was significantly higher than that in WT model group(P < 0.05).Part II: Expression of FLG,CARD14 and TNIP1 in psoriatic lesions(1)FLG:The expression of positive cell ratio was 0.17,0.13 and 0.23 in Ps V group,GPP group and control group,respectively.The difference was statistically significant(H = 8.270,P < 0.05).Compare them in pairs,the control group(0.23)was higher than the Ps V group(0.17),the control group(0.23)was higher than the GPP group(0.13),the difference was statistically significant(P < 0.05);The average protein expression intensity IOD was 208494.24,170926.66 and 310696.66 in Ps V group,GPP group and control group,respectively.The difference was statistically significant(H = 8.620,P < 0.05).Compare them in pairs,The control group(310696.66)was higher than the Ps V group(208494.24),the control group(310696.66)was higher than the GPP group(170926.66),the difference was statistically significant(P < 0.05).(2)CARD14:The expression of positive cell ratio was 0.06,0.06 and 0.03 in Ps V group,GPP group and control group,respectively.The difference was statistically significant(H = 22.747,P < 0.05).Compare them in pairs,Ps V group(0.06)was higher than control group(0.03),GPP group(0.06)was higher than control group(0.03),the difference was statistically significant(P < 0.05).The average protein expression intensity IOD was 106610.95,99327.56 and 59924.27 in Ps V group,GPP group and control group,respectively.The difference was statistically significant(H = 21.121,P<0.05).Compare them in pairs,the Ps V group(106610.95)was higher than the control group(59924.27),GPP group(99327.56)was higher than the control group(59924.27),the difference was statistically significant(P < 0.05).(3)TNIP1:The expression of positive cell ratio was 0.11,0.11 and 0.15 in PsV group,GPP group and control group,respectively.The difference was statistically significant(H = 10.275,P < 0.05).Compare them in pairs,the control group(0.15)was higher than the Ps V group(0.11),the control group(0.15)was higher than the GPP group(0.11),the difference was statistically significant(P < 0.05).The average protein expression intensity IOD was 152176.08,146214.56 and 186265.16 in Ps V group,GPP group and control group,respectively.The difference was statistically significant(H = 11.150,P < 0.05).Compare them in pairs,the control group(186265.16)was higher than the Ps V group(152176.08),the control group(186265.16)was higher than the GPP group(146214.56),the difference was statistically significant(P < 0.05).(4)In the lesions of psoriasis,there is a negative correlation between the IOD value of CARD14 and TNIP1(rs =-0.399,P < 0.05);there is no correlation between the IOD value of FLG and CARD14(rs =-0.032,P = 0.818);there is no correlation between the IOD value of FLG and TNIP1(rs =-0.026,P = 0.850).Conclusion:Part I: Effect of Abnormal Lipid Metabolism on Imiquimod-Induced Psoriasis Mouse Model(1)The lesions of psoriatic dermatitis induced by imiquimod were more intense and the PASI score was higher in Apo E KO mice.It is suggested that abnormal lipid metabolism may affect the degree of inflammation of psoriatic dermatitis.(2)The serum levels of TC,TG,LDL in imiquimod-induced psoriatic dermatitis Apo E KO mice increased significantly,the serum levels of HDL in imiquimod induced psoriatic dermatitis Apo E KO mice decreased significantly.(3)The serum levels of Visfatin and Chemerin in imiquimod-induced psoriatic dermatitis Apo E KO mice increased significantly,suggesting that proinflammatory adipocytokines may be involved in the pathogenesis of psoriasis model with abnormal lipid metabolism.(4)In imiquimod-induced psoriatic dermatitis Apo E KO mice,the expression of several inflammatory factors increased significantly,including IL-1Α,IL-1Β,IL-6,IL-17,IL-12P40/p70,TNF α,IFN gamma.It is suggested that the inflammatory reaction is more significant in the psoriatic model with abnormal lipid metabolism.(5)Abnormal lipid metabolism may have the function of promoting inflammation in the pathogenesis of psoriasis.Part II: Expression of FLG,CARD14 and TNIP1 in psoriatic lesions(1)The expression of CARD14 protein in Ps V and GPP tissues was higher than that in normal skin tissues.The expression of FLG and TNIP1 protein in normal skin tissues was higher than that in Ps V and GPP tissues.(2)There was a negative correlation between CARD14 and TNIP1 protein expression in psoriasis lesions. |
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