Experimental Study Of Tripterygium Glycosides On Psoriasis By Inhibiting IL-27

ObjectiveTo explore the possible mechanism of tripterygium glycosides in the treatment of psoriasis,the effects of tripterygium glycosides on the lesion area,disease severity index score,histopathology and serum interleukin-27 were observed by constructing the model of psoriasis in BALB/c mice induced by imiquimod.MethodsForty SPF BALB/C female mice were randomly divided into five groups:normal group,model group,Tripterygium Glycosides low dose group(9.01㎎﹒kg^-1)、medium dose group(27.03㎎﹒kg^-1)and high dose group(81.09㎎﹒kg^-1),with 8 mice in each group.In addition to the blank group,the right amount of Vaseline was applied on the back,The mice in the other groups were coated with 5%imiquimod cream on their back and right ear at 10 a.m.every day for 7 days.At the same time,The low,medium and high dose groups of twp were given gastric administration with corresponding dose twp solution,0.3 ml﹒d^-1,normal group and model group were given equal volume of normal saline by gavage for 7 days.The changes of skin lesions were recorded daily with camera and scored according to PASI scoring standard;the thickness of right ear was measured with vernier caliper and recorded on the 1st,4th and 7th day respectively;24hours after the last administration,the eyeballs of mice were taken for blood collection and enzyme linked immunosorbent assay（ELISA）was used,ELISA was used to detect the level of IL-27 in serum;embedded sections of skin lesions on the back of mice were taken,hematoxylin eosin（HE）staining was performed,the pathological changes of skin lesions were observed by light microscope and Baker score was performed;Ki67 immunohistochemistry was performed on the pathological sections,The expression of Ki67 positive cells in basal layer was observed and counted under light microscope.Result1.The changes of skin lesions and PASI scores were observed by naked eyes:compared with the model group,the degree of erythema,scales,back skin and right ear thickening in Tripterygium Glycosides groups were improved in varying degrees;from the 4th day,the total PASI scores in the model group,Tripterygium Glycosides low,medium and high dose groups were higher than those in the normal group,The difference was statistically significant（P<0.001）.Compared with the model group,the total PASI scores of mice in each group treated with different doses of tripterygium glycosides were lower than those in the model group（P<0.05,P<0.01or P<0.001）,but there was no dose-dependent relationship.2.Right ear thickness:With the increase of modeling time,the right ear thickness of the model group was gradually increased compared with the normal group,and the difference between the two groups was statistically significant（P<0.001）.Compared with the model group,the right ear thickness of each group treated with different doses of tripterygium glycosides was lower than that of the model group（P<0.01）,but there was no dose-dependent relationship.3.Histopathological changes and Baker score of back lesions:here was no obvious abnormality in the normal group,but in the model group,there were psoriasis vulgaris like pathological changes:hyperkeratosis with parakeratosis,Munro micro abscess was seen in the area of parakeratosis,the granular layer was significantly reduced or disappeared,the spinous layer was hypertrophic,the epidermal process was prolonged,undulating and extending downward,showing club like changes,the spinous layer above the dermal papilla became thinner,the capillaries dilated,and lymphocytes and neutrophils could be seen around cell infiltration.Compared with the model group,the above conditions were significantly improved in the low,medium and high dose tripterygium glycosides groups,and the baker score was also decreased（P<0.05 or P<0.01）,but the baker score was not dose-dependent with tripterygium glycosides.4.Ki67 positive expression and counting results in basal layer of back lesions:only a few positive cells were found in the normal group,but Ki67 positive cells were distributed intensively in the model group.Compared with the model group,the number of Ki67positive cells in each group treated with different doses of Tripterygium wilfordii polyglycosides decreased（P<0.001）,but there was no dose-dependent relationship.5.Serum IL-27 level:compared with the normal group,the level of IL-27 in the model group and the low,medium and high dose group of Tripterygium wilfordii polyglycoside group was significantly increased（P<0.001）.Compared with the model group,the levels of serum IL-27 in mice treated with different doses of Tripterygium wilfordii polyglycosides were decreased（P<0.01 or P<0.001）,but there was no dose-dependent relationship.Conclusion1.TWP has a certain therapeutic effect on psoriasis like lesions in mice,but there is no significant correlation between the therapeutic effect and the dosage of twp.2.TWP may inhibit the occurrence and development of psoriasis by reducing the serum IL-27 level of psoriasis like mice induced by IMQ.