| Objective: Psoriasis is a chronic inflammatory skin disease which seriously affects the quality of life of patients and is easy to combine with a variety of metabolic diseases.The clinical features vary among different regions and races.This article aims to explore the clinical features of patients with psoriasis in Hunan province and the changes of glycolipid metabolism and its mechanism of action during the treatment of acitretin.Part I: Analysis of clinical features and inflammatory indicators of patients with psoriasisMethods:1.This study uses retrospective analysis to analyze the demographic data and clinical features of 2520 cases of psoriatic patients.Psoriasis Area and Severity Index(PASI),Body Surface Area(BSA),Physician’s Global Assessment(PGA)and Dermatology Quality of Life Index(DLQI)and other scores were used to evaluate the severity of psoriasis.A correlation analysis was made between these cases and demographic characteristics.2.The study analyzed the differences between the blood routine parameters of 432 patients with plaque psoriasis and 398 healthy control groups and 5 inflammatory indicators: Systemic immune inflammation index(SII),the neutrophil–lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),monocyte–lymphocyte ratio(MLR)and the ratio of the monocyte count to high-density lipoprotein cholesterol(MHR),exploring the relationship between the indicators above and the PASI score.Results:1.The male-female ratio of 2520 patients with psoriasis was 1.61:1,the average age was 39.84±15.66 years old,724 smoking cases(28.9%),475 drinking cases(18.8%);the main type of desease was plaque,1943 cases(77.1%);1041 cases(41.3%)with scalp as the main onset site.240 cases(9.5%)had hypertension and other comorbidities and 386 cases(15.3%)had a family history.The Body Mass Index(BMI)was 23.48±5.87kg/m2.The average PASI was 8.38±7.82,of which PASI≥10 is 615 cases(29.2%);the average DLQI was 6.69±4.87,of which DLQI≥3 is 1811 cases(71.9%).The PASI score was negatively correlated with educational level and positively correlated with income level and the frequency of smoking and drinking.DLQI was positively correlated with smoking,family history of psoriasis,course of disease,erythrocyte sedimentation rate(ESR)and PASI,and negatively correlated with age of the first onset.2.Compared with the control group,the number of leucocyte counts in patients with psoriasis(6.40±1.70 vs.7.31±1.97)×109/L,neutrophils count(3.62±1.36 vs.4.49±1.67)×109/L,eosinophils count(0.16±0.12 vs.0.18±0.17)×109/L,monocytes count(0.45±0.16 vs.0.53±0.18)×109/L;Percentage of neutrophil(55.73±8.22 vs.60.43±9.22)%,percentage of monocyte(6.95±1.75 vs.7.29±1.92)% and cell distribution width(12.34±1.77 vs.13.36±1.12)were all increased while erythrocyte count(4.73±0.51 vs.4.66±0.47)×1012/L and the percentage of lymphocyte(34.30±7.62 vs.29.35±8.31)% were all reduced,with statistical differnences.3.3.Compared with the control group,these inflammatory indicators of patients with psoriasis were all elevated with statistical differnences: NLR(1.78±0.81 vs.2.36±1.25),PLR(102.86±43.71 vs.108.39±38.6),MLR(0.22±0.08 vs.0.27±0.12),MHR(0.32±0.14 vs.0.38±0.17)and SII(368.48±202.85 vs.496.26±304.97),of which the scores were positively correlated.Part II: A study on the effect and the role of glycolipid metabolism during the treatment of acitretin for patients with psoriasisMethods:1.This study used retrospective analysis to analyse the disease status,treatment plan and blood test data,etc.of 684 patients with plaque psoriasis.The statistics included age,gender,BMI,waist circumference/waist-to-hip ratio,PASI,treatment plan and laboratory results such as blood biochemical examination before and after the treatment of the patients.2.An IMQ-induced psoriasis-like mouse model was constructed to detect the transcription level of IL-23 a,IL-6,TNF-a,IL-17 A,Ki67 and Involucrin in the skin lesions of mouse,as well as the transcription level and immunohistochemical expression of genes such as glucose carrier protein GLUT1,GLUT2,GLUT3,GLUT4 and PPARγ in the skin lesions tissue before and after the treatment of acitretin;to detest the changes of blood glucose,insulin,cholesterol and lipoprotein levels in serum of IMQ mouse before and after the treatment of acitretin,and the oral glucose tolerance test was condected to detect the glucose tolerance status of the mouse;using independent islets to observe the effect of acitretin on iselet function and insulin release,detecting the transcription level of glycolipid metabolism-related genes such as Pdtx-1,Sirt1,Pparγand Tfam in mouse lslet tissue.Results:1.Compared with the healthcontrol group,there was no significant difference in blood lipid level in patients with psoiasis(P>0.05),while the fasting blood glucose level was higher than that in the health control group(5.76±1.31 vs.5.38±1.14 mmol/L,P < 0.001).After the treatment of acitretin,the levels of triglyceride and Low Density Lipoprotein(LDL)increased while the levels of High Density Lipoprotein(HDL)and BMI values decreased significantly,and the levels of blood glucose obviously decreased either(5.71±0.91 vs.5.55±0.76,P=0.0019).2.Acitretin can significantly improved the skin lesion of IMQinduced psoriasis-like mouse by down-regulating the transcriptional levels of Il-23 a,Il-6 and Ki67,and up-regulating the transcriptional levels of Involucrin,but there appeared no changes in Tnf-a and Il-17 a.The peripheral blood glucose level of IMQ psoriasis-like mouse decreased as well as the level of cholesterol,total lipoprotein,low density lipoprotein and high density lipoprotein,while the level of insulin increased.The independent islet test found that acitretin can reduce the insulin secretion level of IMQ mouse,bringing the blood glucose level lowered by IMQ back up and restoring the insulin sensitivity.After IMQ intervention,islet homeostasis was impaired,and the transcription level of Pdx-1 gene increased,the transcription levels of Sirt1 and Pparγ gene decreased,which could be partially recovered after the treatment of acitretin.3.Compared with the control group,the uptake of 2-NBDG was significantly increased after the treatment of acitretin to Hep G2 cells.At the same time,the transcript-level expression of glucose transporter genes GLUT1 and GLUT4,glycogen synthesis-related genes AKT1 and GSY2,lipid synthesis-related genes ACC1,MGAT1,BSCL2 and FASN gene expression genes were significantly increased in Hep G2 cells after the treatment of acitretin,while the glycoconogenic gene G6 Pase expression was significantly decreased.Acitretin significantly promoted the formation of lipid droplets induced by oleic acid in Hep G2 cells.Conclusion:1.This study preliminarily clarifies the clinical features of psoriasis patients,and finds that the inflammatory indicators NLR,PLR,MLR,MHR and SII of psoriasis patients are positively correlated with the severity of psoriasis disease PASI,which may be meaningful for assessing the severity of psoriasis.2.Psoriasis can cause imparied blood glucose homeostasis.Its fasting blood glucose concentration is higher than that of the control group.After the acitretin treatment,the blood glucose level of patients with psoriasis decreased significantly,and the level of triglycerides increased significantly.3.In the mouse model of IMQ-induced acute psoriasis-like dermatitis,IMQ-induced excessive insulin secretion in mouse pancreatic islets leads to a significant drop in blood sugar in mouse.Acitretin can inhibit the mass release of IMQ-induced insulin,thus maintaining glucose homeostasis in mouse.4.Acitretin reduces the body’s blood sugar level in multiple ways.On the one hand,it promotes acitretin to promote the glycogen synthesis of hepatocytes by increasing the intake of extracellular glucose through cells such as liver cells,and inhibits gluconeogenesis.In addition,acitretin promotes the lipid synthesis in liver cells. |
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