Mechanism And Effects Research Of Shugan Jianpi Yichang Decoction On The Mice With Psoriasis Based On Brain-gut-skin Axis

Objective To explore the therapeutic effect and mechanism of Shugan Jianpi Yichang decoction on psoriasis mice,and to preliminarily clarify the potential role of it plays on brain-gut-skin axis in the psoriasis.Methods 80 KM mice were randomly divided into normal group,model group,the high-dose,medium-dose and low-dose group of Shugan Jianpi Yichang decoction,16in each.Binding stress and drink acetic acid stimulation combined with imiquimod cream were used to induce psoriasis mice model except for the normal group.While the normal group and the model group given 0.1m L/10g of distilled water,the high-dose,medium-dose and low-dose group of Shugan Jianpi Yichang decoction were given gavage at the doses of 17.8,8.8 and 4.4m L/kg respectively,for 21 days once a day.The behavioral characteristics and PASI scores were observed before and after treatment.Eight mice from each group were randomly selected of pretherapy and the 7th,14th and 21st day of the treatment process,measuring fecal score and fecal water content.HE staining was used to observe the pathological changes of skin and intestinal tissues.ELISA was used to detect the contents of IFN-γ,IL-4,TNF-α,IL-23 and IL-17 in serum,the content of 5-HT,DA and NE in brain tissue,the content of VIP and 5-HT in intestinal tissue.Immunohistochemical method was used to detect the optical density value content of IFN-γand IL-4 in skin tissue.The Western-Blot method was used to analyse the expression of SOCS3 and STAT3 proteins in brain,intestine,and skin tissues.Results Compared with the normal group,the behavioral scores decrease in model group,high-dose,medium-dose and low-dose group of Shugan Jianpi Yichang decoction preadministration(~aP<0.05);after administration,compared with the model group,the behavioral scores increase in high-dose and medium-dose group of Shugan Jianpi Yichang decoction(~bP<0.05),and there was no significant difference with the normal group(~aP>0.05),while the low-dose group had no significant effect on the behavioral scores.Compared with the normal group,the PASI score increase in model group,high-dose,medium-dose and low-dose group of Shugan Jianpi Yichang decoction preadministration(~aP<0.05);after administration,compared with the model group,the behavioral scores showed no significant difference in high-dose,medium-dose and low-dose group of Shugan Jianpi Yichang decoction(~bP>0.05),high-dose and medium-dose group of Shugan Jianpi Yichang decoction showed difference with the normal group(~aP<0.05),while the low-dose group was no significant difference with the normal group(~aP>0.05).Compared with the normal group,the Bristol score decrease in the medium-dose group of Shugan Jianpi Yichang decoction and fecal water content of the model group and the medium-dose and low-dose group of Shugan Jianpi Yichang decoction preadministration(~aP<0.05),after administration,compared with the model group,the Bristol score increase in the high and medium dose groups(~bP<0.05),while the medium and low-dose group showed no significant difference with the normal group(~aP>0.05),and the fecal water content increase in the high-dose group(~bP<0.05),while the high,medium and low-dose group showed no significant difference with the normal group(~aP>0.05).The normal group had complete skin structure,and no abnormal lesions were found.The epidermis of mice in the model group was significantly thickened,and different degrees of hyperkeratinization,the epidermal protrusions were significantly extended,spinous hypertrophy,thinning of the granular layer.The skin pathological changes of mice in the drug group were similar to those in the model group,but the pathological changes were lighter than those in the model group,especially the skin pathological improvement was the most significant in the high-dose group.The results of intestinal histopathology showed that the colon tissue structure of mice in the normal group was intact,and no abnormal lesions were found.In the model group,the colon tissue of mice showed obvious neutrophil infiltration,epithelial cell damage,abnormal structure of colorectal glandular cells,loss of crypts,and deletion of most goblet cells.The histopathological changes of mice in the drug delivery group were similar to those in the model group,but the pathological changes were lighter than those in the model group,especially the high-dose group had the most significant histopathological improvement.Compared with the normal group,the contents of IFN-γ,TNF-α,IL-23,IL-17 and IL-4 in serum increased significantly(~aP<0.05);compared with the model group,the contents of IFN-γ,TNF-α,IL-23 and IL-17 in serum decreased significantly(~bP<0.05).Compared with the normal group,the contents of 5-HT and NE in the brain tissues increased significantly(~aP<0.05),while the high-dose and middle-dose group of Shugan Jianpi Yichang decoction of the contents of DA in the brain tissues increased(~aP<0.05);compared with the model group,the contents of 5-HT and NE in brain tissues of high-dose and middle-dose group of Shugan Jianpi Yichang decoction decreased significantly(~bP<0.05),while the decreased not significantly in the low-dose group(~bP>0.05).Compared with the normal group,Compared with the normal group,the contents of VIP and 5-HT in the intestinal tissues increased significantly(~aP<0.05),compared with the model group,both VIP and 5-HT contents in intestinal tissues of high-dose group of Shugan Jianpi Yichang decoction decreased significantly(~bP<0.05),and5-HT contents in intestinal tissues decreased significantly in the middle dose group(~bP<0.05),while the low-dose group showed no significant difference(~bP>0.05).The optical density value of IFN-γin the skin tissue decreased(~aP<0.05)and the optical density value of IL-4 increased(~aP<0.05);compared with the model group,the average optical density of IFN-γskin tissues in the high-dose and the medium dose groups increased significantly(~bP<0.05),while the low-dose group showed no significant difference(~bP>0.05).Compared with the nomal group,the expression of SOCS3 in brain and skin tissues in model group and the expression of SOCS3 in intestine tissues increase in medium-dose,low-dose group of Shugan Jianpi Yichang decoction(~aP<0.05),while the expression of STAT3 in brain,intestine and skin tissues increase in model group(~aP<0.05);compared with the model group,the expression of SOCS3 in brain tissues of high-dose,medium-dose and low-dose group of Shugan Jianpi Yichang decoction and the expression of SOCS3 in intestine tissues decrease in high and medium dose(~bP<0.05),but the use of Shugan Jianpi Yichang decoction had no obvious effect on reducing the expression of SOCS3 in skin tissues;the expression of STAT3 protein in brain,intestines and skin tissues decrease in high-dose,medium-dose and low-dose group of Shugan Jianpi Yichang decoction(~bP<0.05).Conclusion 1.The mice model of psoriasis induced by binding stress and drink acetic acid stimulation combined with imiquimod cream showed obvious erythema and scale.2.Shugan Jianpi Yichang decoction can achieve the therapeutic effect of psoriasis by soothing the liver and relieving depression,strengthening the spleen and moistening the intestine.The mechanism is closely related to the expression of cytokines and proteins in the brain-gut-skin axis,which are specifically manifested as down-regulation of IFN-γ,TNF-α,IL-23 and IL-17 in serum,the content of 5-HT and NE in brain tissue,the content of VIP and 5-HT in intestinal tissue,up-regulated the average optical density content of IFN-γin skin tissue,and down-regulated the expression of SOCS3 protein in brain,intestinal tissue,and down-regulated the expression of STAT3 protein in brain,intestine and skin tissue.