| Theoretical ResearchProfessor Li Ping's Experience in Treating Psoriasis with Modified Xiaoyaosan Xiaoyaosan came out of the Song Dynasty TaiPingHuiMinHeJiJuFang,which is mainly for liver stagnation,blood deficiency and spleen weakness.Moreover,it was inherited and developed by later generations of physicians.From now,it is widely used in clinical internal medicine,gynecology,dermatology and other diseases.This article introduces the etiology and pathogenesis of psoriasis,the principle of application of Xiaoyaosan and the analysis of prescriptions,the relationship between psoriasis and emotions,research on Xiaoyaosan's regulation of emotions and typical cases.It summed up Professor Li Ping's thoughts and experience in the clinical application of Xiaoyaosan with the syndrome-based treatment of psoriasis with liver depression and spleen deficiency.Professor Li Ping combined with the syndrome differentiation of "Essence,Qi,blood and body fluid",analyzed the relationship between the physiological function of the liver and psoriasis.Paid attention to the Qi stagnation as the initial link of psoriasis,the therapeutic effect of the liver governing regulating and regulating Qi machine on psoriasis,and the pathogenic role of emotional factors.She also analyzed the source of its heat evil,which provided new ideas for the treatment of psoriasis.Experimental StudyExperiment 1:Observe the Depressive Behavior of Imiquimod-induced Psoriasis-like Mouse ModelObjective:Observe whether the imiquimod-induced psoriasis mouse model has depressive behavior,whether this animal model has liver depression and spleen deficiency syndrome.Method:Forty-five SPF grade male BALB/c mice.The hair on the back of the mice was shaved.The mice were randomly divided into the five groups,including the control group(Control),the model group(Model),the methotrexate group(MTX),the fluoxetine group(F luoxetine)and the fluoxetine combined with methotrexate group(Fluoxetine-MTX).Daily 5%imiquimod cream(Imiquimod,IMQ)was applied to the back of mice to induce psoriasis-like skin lesions for eight days.Psoriasis area and severity index(PASI)was used for daily scoring.Histological changes and epidermal thickness of skin lesions were observed under a light microscope.The expression of Ki67 and CD3+T lymphocytes in skin lesions were observed by immunofluorescence and immunohistochemistry.A high-throughput liquid protein microarray was used to detect the secretion of inflammatory cytokines in skin lesions.Observed the changes in the body mass of mice.The sugar water preference experiment and the open field experiment evaluated the differences in depressive behavior of mice in each group.The content of neurotransmitters such as 5-hydroxyindoleacetic acid(5-HIAA),5-hydroxytryptamine(5-HT),Adrenaline(Ad),Dopamine(DA),Glutamic acid(Glu)and Herpes virus ateles(HVA)in the prefrontal cortex,hippocampus and hypothalamus of mice were determined by liquid chromatography-mass spectrometry(HPLC-MS).Result:Compared with the Control group,the Model group had skin lesions with hypertrophic squamous hyperplasia,severe infiltration,and erythema.The thickness of the epidermis,the expression of Ki67 and CD3+T lymphocyte,the content of inflammatory cytokines such as IL-12p70,IL-17A and IL-23 of the Model group were all increased(P<0.05),and the content of IL-10 was decreased(P<0.01).Compared with the Model group,the IL-10 content of the treatment group was increased(P<0.05),and the expression levels of other indicators of the treatment groups were decreased(P<0.05).The body mass change of the Control group was smaller than that of the Model group(P<0.01).Compared with the Control group,the sugar water preference rate of the Model group was significantly reduced(P<0.01),and the central area distance and central area time of Model group were significantly reduced(P<0.01).The content of 5-HT,Ad,3,4-Dihydroxyphenylaceticacid(DOPAC),Noradrenaline(NE)and ?-aminobutylic acid(GABA)in different brain regions of the Model group were significantly reduced(P<0.05).Compared with the Model group,the treatment groups had some improvement in the above indicators.Besides,IMQ-induced psoriasis-like mice had messy and yellowish hair,low spirits,significant declined body mass,and there was a macroscopic characterization of liver depression and spleen deficiency.The sugar water preference experiment and the open field behavior experiment showed that the psoriasis-like mice had depressive behavior.The content of neurotransmitters in different brain regions was down-regulation.These objective indicators were consistent with the syndrome of liver depression and spleen deficiency.Conclusion:Imiquimod applied for eight days can cause psoriasis-like lesions and depression in mice.This model may have a syndrome of liver depression and spleen deficiency.Experiment 2:Interventional Effect of Xiaoyaosan on Imiquimod-induced Psoriasis-like MiceObjective:To observe the effect of Xiaoyaosan on imiquimod-induced psoriatic skin lesionsand depressive behavior.Method:Thirty-six SPF grade male BALB/c mice were randomly divided into blank control group(Control),model group(Model),methotrexate group(MTX)and Xiaoyaosan high,medium and low dose groups(XH,XM,XL).5%imiquimod cream was applied on the back to induce psoriasis-like lesions in mice.Psoriasis area and severity index(PASI)was used for daily scoring.Histological changes and epidermal thickness of skin lesions were observed under a light microscope.The expression of CD3+T lymphocytes in skin lesions was observed by immunohistochemistry,and the expression of Ki67 in skin lesions was observed by immunofluorescence.Observe the general state of mice,body mass change,sugar water:preference and open field experiment daily to explore the behavioral differences of mice.Result:Compared with the Control group,the Model group had hypertrophic scaly lesions,severe infiltration,and erythema.The PASI score increased,epidermis thickened significantly,Ki67 and CD3+T cell expression levels in skin lesions increased significantly(P<0.001).The back skin lesions of mice in the treatment groups were significantly improved compared with the Model group,and the PASI score and epidermal thickness were significantly lower than the Model group(P<0.05).The expression levels of Ki67 and CD3+T cells in the skin lesions of the treatment groups were significantly lower than that of the Model group(P<0.05).Compared with the Control group,mice in the Model group had messy hair,lack of energy,and poor general condition,the change of body mass before and after modeling was significant,the sugar water preference rate was decreased(P<0.01).In the open field environment,the total distance traveled,average speed,time in the central area,and distance in the central area of the Model group mice were all reduced(P<0.05).However,the general status of mice with psoriasis-like mice in each dosage group of Xiaoyaosan was improved,the rate of sugar waterpreference was increased,and various indicators of the open field behavior were increased.Conclusion:Xiaoyaosan not only relieves imiquimod-induced psoriasis-like skin lesions inmice but also improves its depressive behavior.Experiment 3:Study on the Mechanism of Xiaoyaosan in the Treatment of Imiquimod-induced Psoriasis-like Mouse Model Objective:To observe the effect of Xiaoyaosan on inflammatory cytokines,inflammatory signaling pathways,and depression-related neurotransmitters in imiquimod-induced psoriasis-like mouse model lesions.Method:Thirty-six SPF grade male BALB/c mice were randomly divided into blank control group(Control),model group(Model),methotrexate group(MTX)and Xiaoyaosan high.medium and low dose groups(XH,XM,XL).5%imiquimod cream was applied on the back to induce psoriasis-like lesions in mice.A high-throughput liquid protein microarray was used to detect the secretion of inflammatory cytokines in skin lesions.Western blot assay to detect phosphorylation levels of Nuclear factor kappa-B(NF-?B p65)and p38 Mitogen-activated protein kinase(p38 MAPK)in skin lesions.The content of DA,5-HT and Ad in the prefrontal cortex,hippocampus and hypothalamus of the mice was declined by HPLC-MS.Pearson correlation and Spearman rank correlation were used to analyze the correlation between PASI score and the contents of DA,5-HT and Ad in the prefrontal cortex,hippocampus and hypothalamus of mice.Result:Compared with the Control group,the content of IL-12p70,IL-17A,IL-18,IL-23 and TNF-? in the skin lesions of the Model group was significantly increased(P<0.01),and the content of IL-10 was significantly reduced(P<0.01).However,the content of the above inflammatory cytokines in each dosage group of Xiaoyaosan was decreased to varying degrees compared with the Model group(P<0.05),and the content of IL-10 was increased significantly(P<0.05).The NF-?B p65 and p38 MAPK phosphorylation levels in the skin lesions of the Model group were significantly higher than that of the Control group(P<0.01),the phosphorylation level of p38 MAPK in the skin lesions of mice in the Xiaoyaosan low-dose group was significantly lower than that in the Model group(P<0.05).The content of 5-HT,Ad,NE,GABA and other neurotransmitters in different brain tissues of the Model group was lower than that of the Control group(P<0.05).The content of 5-HT and Ad in different brain regions of mice in each dosage group of Xiaoyaosan was increased significantly compared with the Model group(P<0.05),and the content of Glu was decreased(P<0.05).In addition,the PASI score of psoriasis-like mice is negatively correlated with the content of 5-HT,NE,Ad and GABA in different brain tissues.Conclusion:The imiquimod-induced psoriasis-like mice PASI score was negatively correlated with the expression of depression-related neurotransmitters,and the degree of depression increased with the increase of psoriatic lesions.Xiaoyaosan can alleviate the inflammation of psoriasis by reducing the release of local inflammatory cytokines and inhibiting the phosphorylation of NF-?B p65 and p38 MAPK in skin lesions.At the same time,it could up-regulate the expression level of depression-related neurotransmitters and improves depression in mice.Xiaoyaosan,which has the effect of relieving liver and spleen,had a therapeutic effect on IMQ psoriasis-like mice.Therefore,it was proved that this mouse model has the syndromes of liver depression and spleen deficiency by the reverse thinking mode of " testing syndromes with prescriptions",which was consistent with the clinical and could be used for the pharmacodynamic study of Xiaoyaosan. |
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