| BackgroundPsoriasis is one of the common diseases of dermatology,which is characterized by infiltration of erythema in the lesion area,covered with silver-white scales as the main manifestation of inflammatory diseases,the course was slow and easy In some seasons or climatic conditions induced by recurrence,the current treatment of drugs can only effectively alleviate the symptoms of psoriasis,can not completely cure.Psoriasis worldwide accounts for about 2%to 3%of the total population,and the distribution of psoriasis is characterized by ethnic and regional differences,among which white and high-latitudes of psoriasis The rate is higher for other regions.In 1984,the prevalence of psoriasis was investigated by Chinese scholars.The results showed that the prevalence of psoriasis was 0.123%in China.The analysis showed that the prevalence of psoriasis was higher in the northern region than in the southern region.In 2006,the epidemiological survey of psoriasis in six provinces and cities in China showed that the prevalence of psoriasis had increased to 0.47%.According to the survey,there were more than 7 million psoriasis patients in China.According to the symptoms of different patients will be divided into psoriasis vulgaris,arthritis,pustular disease and erythrodermic type of these four types,of which the prevalence of psoriasis vulgaris as high as 97%,the most common in clinical,And more than 90%of psoriasis patients with recurrence problems,the pathogenesis of complex,immune factors is a very important factor,in which the role of macrophages in the pathogenesis of psoriasis increasingly people’s attention.PSORI-CMO2 by the red peony,swollen wind,soil Fulling,Curcuma and other components,from the doctor of traditional Chinese medicine Professor Guo Guowei treatment of psoriasis prescription,by Lu Chuanjian vice president of continuous optimization derived.PSORI-CM01 and PSORI-CMO2 side drugs have immunomodulatory effects,Fang red peony,soil Fuling,etc.have been shown to inhibit the secretion of inflammatory factors,can regulate the function of macrophages,psoriasis patients with skin characteristics of the dermis Inflammatory cell infiltration based on macrophages,T cells,dendritic cells,and natural killer cells.Studies from the genetically psoriasis mouse model have shown that macrophages may be involved in classes Psoriasis skin inflammation.The previous work shows that PSORI-CMO2 can effectively inhibit the excessive proliferation of epidermal keratinocytes,inhibit the model of pruritus in mice and the secretion of inflammatory factors,affect the cell cycle of epidermal keratinocytes,promote the apoptosis of epidermal keratinocytes,and prolong the G2/M,while PSORI-CMO2 can affect epidermal keratinocytes in the relevant inflammation and cell cycle gene and protein expression.But the whole study of macrophages has not yet been carried out,so we speculate that PSORI-COM2 may also affect the function of psoriatic lesions in macrophages,inhibit the expression of psoriasis-associated inflammatory factors,Snake disease work.ObjectiveThe aim of this study was to investigate the pharmacological effects of PSORI-COM2 and the therapeutic effect on the model of psoriasis in mice,and to further clarify the mechanism of PSORI-COM2 and the scientific connotation of the disease.Mehtods1.Establishment of Balb/C Mouse Psoriasis Model Induced by Imiquimod Mouse dorsal skin hair removal,area of about(2*3cm),Hair removal The next day in the hair removal site coated with imiquimod,continuous smear for 7 days,observe the mouse weight,back skin erythema,scales,infiltration,the PASI score.The levels of TNF-a,IL-6,IL-4 and IL-1β in serum were measured on the 7th day,and the skin of the dorsal skin was stained by HE staining and immunohistochemistry.The imiquimod Preparation of psoriasis model.2.Therapeutic effect of PSORI-CMO2 on psoriasis mice The mice were divided into normal group,model group,methotrexate group and PSORI-CMO2 low,medium and high dose group.Two days before modeling,PSORI-CMO2 was given to the PSORI-CMO2 group.Mouse dorsal skin was depressed,coated with imiquimod(except for normal),and administered continuously for 7 days(ie,normal group,model group given water).The weight of the mice was observed,the erythema of the back skin,the scales and the infiltration,and the PASI score was given.3.Effects of PSORI-CMO2 on Inflammation and Protein in Psoriasis Mice Fasting after the last administration,the eighth day of the mice were sacrificed.The levels of TNF-a,IL-6,IL-4 and IL-1β were detected by Elisa kit.The expression of TNF-a,IL-6,IL-10,IL-1β and iNOS in the dorsal skin of mice were detected by RT-PCR.The expression of TNF-α,IL-6,IL-1β and iNOS were detected by immunohistochemistry.To evaluate the expression of CD3,Ki67 and F4/80 proteins in the dorsal skin of mice,and to evaluate the therapeutic effect of PSORI-CMO2 on psoriasis lesions induced by imiquimod in Ba1B/C mice.4.Effects of PSORI-COM2 on the Growth of Different Macrophages Polarization of RAW264.7 cells induced by LPS(1μg/ml)and IL-4(20ng/ml)was performed to detect Ml and M2 macrophages.MTT was used to detect different concentrations of PSORI-CMO2(5%,10%,15%)On the proliferation of RAW264.7 cells.5.Effects of PSORI-COM2 on Polarized Macrophage-associated Proteins RAW264.7 cells were induced to polarize M1 and M2 macrophages with final concentration of LPS(1 μ g/ml)and IL-4(20ng/ml),and different concentrations of PSORI-CMO2(5%,10%,15%)The expression of Arg-1,Ym-1,Fizz-1 and IL-10 in TNF-α,IL-23A,IL-1β,iNOS and M2 macrophages of M1 macrophages were detected by RT-PCR.The expression of p-STAT1,STAT1,p-STAT6 and STAT6 were detected by Western-blot.Result1.5%imiquimod 62.5mg can induce the erythrocytes of Ba1B/C mice to prepare the pathological model of psoriasis.The model can last for 7 days.TNF-a and IL-1β in the dorsal skin tissue of mice,INOS mRNA was significantly increased.2.PSORI-CMO2 significantly improved the body weight of psoriasis mice and back skin erythema,scales,infiltration symptoms,reduce imiquimod-induced psoriasis mice PASI score.The results of HE staining showed that PSORI-CMO2 could inhibit the lesion of psoriasis model.The results of RT-PCR showed that PSORI-CMO2 could decrease the expression of TNF-a,IL-10 and iNOS in the dorsal skin of mice and increase the expression of IL-6 mRNA.The expression of Ki67,CD3 and F4/The Compared with the model group,the low and medium dose of PSORI-CMO2 could inhibit the release of TNF-α.The high concentration of PSORI-CMO2 could inhibit the release of IL-1β in the ELISA experiment.High doses of PSORI-CMO2 can promote the release of IL-4 and IL-6.3.IL-4(20ng/ml)can lead to the polarization of RAW264.7 cells to M2,and in the absence of macrophages,the expression of IL-4(IL-4)PSORI-CMO2 serum containing different concentrations had no effect on the growth of mouse peritoneal macrophages.In the macrophage polarization state,different concentrations of PSORI-CMO2 serum containing different concentrations of serum on the growth of mouse macrophages M1 mice have a certain inhibitory effect,which 24h,the low concentration of PSORI-CMO2 serum Ml and RAW264.7 cells had a certain inhibitory effect.At 48h,the concentration of PSORI-CMO2 could inhibit the activity of RAW264.7 cells.The concentration of PSORI-CMO2 in different concentrations of PSORI-CMO2 could enhance the growth of M2 type RAW264.7 cells.The effect of low,medium and high concentration of PSORI-CMO2 on the activity of M2 RAW264.7 cells had no effect at 48h.4.The results of RT-PCR showed that PSORI-CMO2 could decrease the expression of TNF-α,IL-23A,IL-1β and iNOS in M1W RAW264.7 cells.The serum of PSORI-COM2 could up-regulate M2 RAW264.7 cells Arg-1,Ym-1,Fizz-1,IL-10 mRNA expression.The results of ELISA showed that PSORI-CMO2 could decrease the release of IL-1β in Ml macrophages and increase the release of IL-6 in M2-macrophage s.5.The expression of p-STAT1 protein was down-regulated by PSORI-CMO2 serum,and the expression of p-STAT1 protein was up-regulated.Conelusion1.PSORI-CMO2 by reducing the expression of skin inflammatory factors,repair damaged skin symptoms,imiquimod-induced psoriasis mice have a therapeutic effect.2.The expression of Arg-1,Ym-1,Fizz-1 and IL-10 in M2 RAW264.7 cells was up-regulated by downregulation of TNF-α,IL-1β and iNOS in M1 RAW264.7 cells Macrophage polarization affect the psoriasis microenvironment and thus play a role in the treatment of psoriasis.3.The expression of NF-kB and STAT1 signaling pathway improved the expression of M1-RAW264.7 cells in psoriasis and adjusted the expression of STAT6 signal pathway to improve the expression of M2 RAW264.7 cells in psoriasis. |
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