Clinical And Experimental Study Of Psoriasis Associated With Kidney Injury

Psoriasis is a multi-system inflammatory disease where the skin and the joints a re the primary targets.There are many reports that psoriatic patients tend to have con current illnesses that are termed as comorbidities.Part 1 An overview of psoriasis and its concomorosisPsoriasis is a common chronic inflammatory skin disease associated with abnormal genetic background and immune response,which can be accompanied by multiple system damage.Many scholars at home and abroad have studied the pathogenesis of this disease,but the specific pathogenesis is not clear.With the deep understanding of psoriasis,more and more scholars believe that the disease can also be involved in the visceral organs.Psoriasis co morbidity is also a hot research topic in recent years.A large number of epidemiological surveys show that besides skin damage,it can also involve eye,liver,gastrointestinal tract(ulcerative colitis),cardiovascular,kidney and many other organs.The risk of comorbidity is positively related to the severity of psoriasis,and most of the co-diseases have clinical manifestations after the occurrence of psoriasis.Long term secretory proinflammatory cytokines,such as tumor necrosis factor-alpha,and so on,repeated inflammatory stimulation,may lead to insulin resistance and metabolic syndrome.These inflammatory mediated immune responses and the occurrence of comorbidity may have comnon cytokine.The pathogenesis of psoriasis is closely related to inflammation.Thl and Thl mediated inflammatory reaction and inflammatory mediators such as IL-6,IL-12,IL-17,IL-22,IL-23 and TNF-alpha play an important role in the pathogenesis of psoriasis.Patients with psoriasis often have kidney damage,resulting in impaired renal function and great harm to the human body.Through data analysis of past patients,it is found that the risk of kidney disease is significantly increased in psoriasis patients,and the probability of severe psoriasis complicated with chronic kidney disease will be higher.TNF-alpha,IL-6 and other cytokines not only play an important role in renal damage,but also play an important role in the pathogenesis of psoriasis.Psoriasis is a chronic,inflammatory and recurrent skin disease mediated by multiple genes.There are many clinical e-vidences that kidney damage is one of its multiple complications.However,the pathogenesis is not clear yet.Part 2 Clinical study of renal damage induced by psoriasisObjective Kidney involvement secondary to psoriasis is a controversial issue.In this study,we evaluated the prevalence of urinary abnormalities in patients with psoriasis.Materials and methods 97 psoriasis vulgaris patients and 96 age and gender-matched control subjects without hypertention or diabetes were enrolled in the study.Psoriasis area and severity index was used to assess the severity of psoriasis.Analyse the urea,and 24-h protenuria,albuminuria,RBP,NAG were measured in all patients and controls.Results The patients with psoriasis had an increased prevalence of pathological albuminuria,protenuria compared with controls(P<0.05).The psoriasis area and severity index scores in psoriasis patients correlated significantly with 24-h albuminuria.Conclusion The increased prevalence of pathological albuminuria,ptoteinuria and the positive correlation with psoriasis severity may suggest subclinical glomerular dysfunction in these patients.Part 3 Experimental study and mechanism of renal injury caused by psoriasisObjective:Objective to elucidate the mechanism of renal injury induced by psoriasis vulgaris.Methods:BALB/C mice were treated with 5%Imiquimod Cream(50mg),1 time/day for 7 days,and the model of psoriasis in mice was made.The experiment was divided into 4 groups:blank control group(blank group),model group,positive regulation of lipopolysaccharide group(LPS group)and negative regulation of dexamethasone group(group DEX).The blank control group with Vaseline daub after intraperitoneal injection of normal saline,7 consecutive days;the model group,with 5%Imiquimod Cream after intraperitoneal injection of saline,continuous 7 days;group LPS,with 5%Imiquimod Cream in the day after,then intraperitoneal injection of LPS,0.1 mg/kg;group DEX,with 5%Imiquimod Cream in every day.After intraperitoneal injection of dexamethasone,0.1 mg/kg.Mice in each group were killed after eighth days of experiment.We detected the changes of mouse skin lesions and renal function,serum and renal levels of inflammatory cytokines in serum and kidney,MDA and SOD activity,renal pathological examination,24 hours urine protein,kidney CD2AP and podocin protein expression,TLR/NF-kappa B pathway related protein expression.Results:In the model group on the second day,the back skin showed a pale red;third days and a small amount of skin thickening,erythema and scales;fourth to fifth days,and continued to increase more scaly erythema,gradually thickening of the skin;sixth to seventh days,skin lesions to reach the maximum,and showed the typical lesions of psoriasis.In the model group,serum creatinine and urea nitrogen content increased significantly(P<0.01);the serum creatinine and urea nitrogen content of LPS group increased further(P<0.05);compared with the model group,the serum creatinine and urea nitrogen content of DEX group decreased significantly(P<0.05).Serum and kidney group in a mouse model of IL-1 beta,IL-6,TNF-alpha,IL-17 and IL-22 were significantly increased(P<0.01);compared with the model group,the serum levels of LPS mice in IL-6,IL-1 beta,TNF-alpha,IL-17 and IL-22 levels increased(P<0.05);compared with the model group.The serum of mice in DEX group in IL-6,IL-1 beta,TNF-alpha,IL-17 and IL-22 were significantly decreased(P<0.05).The content of MDA in serum and kidney in mice of model group increased significantly(P<0.01),the activity of SOD was significantly decreased(P<0.01);compared with the model group,the serum levels of MDA in LPS group were increased(P<0.05),the activity of SOD further decreased significantly(P<0.05);compared with the model group.The MDA content in serum of mice in DEX group decreased significantly(P<0.05),the activity of SOD was significantly increased(P<0.05).Kidney pathological examination of HE staining showed that the model mice glomerular volume increased,capillary basement membrane thickened and mesangial matrix hyperplasia,tubular epithelial cells with vacuolar lesions,see protein tube;compared with the model group,LPS group,to further promote the mouse kidney injury;compared with the model group,DEX group,kidney the degree of injury was significantly reduced,glomerular morphology was normal,visible part of thickening of basement membrane,mild mesangial hyperplasia,only a small number of renal tubular epithelial cell vacuolation,lesion degree was significantly lighter than the model group.Kidney pathological examination of PAS staining showed that the ratio of kidney tissue in the model group positive staining area and glomerular area tangent increased significantly;compared with the model group,the LPS group further increased the mouse kidney tissue staining positive area,induced glomerular hypertrophy,basement membrane thickening and mesangial hyperplasia;DEX mice kidney tissue positive staining area,inhibition and improve glomerular hypertrophy,basement membrane thickening and mesangial hyperplasia.The 24 h urine protein of model group were significantly increased(P<0.01);compared with the model group,after 7 days in group LPS,the amount of urine protein in mice increased significantly(P<0.05);compared with the model group,DEX group improved the amount of urine protein in mice,seventh days,24 h urine protein the amount of DEX group were significantly lower(P<0.05).Kidney tissue in mice model of podocin and CD2AP protein expression were decreased(P<0.01);compared with the model group,the renal tissues of mice in the LPS expression of podocin and CD2AP protein were significantly decreased(P<0.05);compared with the model group,DEX group,podocin in renal tissue of mice CD2AP protein expression increased significantly(P Tatsuya<0.05).The expression of NF-kappa Bp65 in the kidney of psoriasis mice increased significantly(P<0.01).Compared with the model group,the expression of NF-kappa Bp65 in the LPS group increased significantly(P<0.05),and the expression of NF-kappa Bp65 in DEX group decreased significantly(P<0.05).The expression of I kappa B alpha in the kidney of psoriasis mice was significantly decreased(0.60 + 0.06)(P<0.05).Compared with the model group,the expression of I kappa B alpha was significantly decreased(P<0.05)in the group LPS(P<0.05),and the expression of I kappa B a(0.66 + 0.07)in DEX model group was significantly increased(P<0.01)compared with the model group.The expression of MyD88 protein(0.68 + 0.06)in the kidney of psoriatic mice increased significantly(P<0.01).Compared with the model group,the expression of MyD88 protein in the kidneys of group LPS(0.85 + 0.10)increased significantly(P<0.05).Compared with the model group,the expression of MyD88 protein(0.53 + 0.07)in the kidneys of group DEX was significantly decreased(P<0.05).The expression of TLR2 and TLR4 in the kidney of psoriasis mice increased significantly(P<0.01).Compared with the model group,the expression of TLR2 and TLR4 in the LPS group increased significantly(P<0.05),and the expression of TLR2 and TLR4 in DEX group was significantly lower than that in the model group(P<0.05).Conclusion:Psoriasis induced renal injury and activated the TLR receptor on the basis of skin lesions,promoted the expression of TLR2,TLR4 and so on,and then activated the expression of MyD88 protein.MyD88 protein further activated the expression of NF-kappa B related protein,the expression of NF-kappa Bp65 protein was increased,I?B? protein was reduced.The levels of inflammatory factors such as IL-1?,IL-6,TNF-a,IL-17 and IL-22 were increased,which caused renal tubules and glomerular podocytes and glomerular mesangial cells and eventually led to renal renal damage.