The Role And Mechanism Of Sirt6 In Podocyte Injury In Patients With Lupus Nephritis

Objective: To study the relationship between Sirt6 and podocyte damage in patients with lupus nephritis(Lupus nephritis,LN),and to explore its possible mechanism,to provide new ideas for the diagnosis and treatment of LN.Methods: From September 2018 to September 2020,80 patients who were hospitalized in the Department of Nephrology,Qingdao University Affiliated Hospital and were diagnosed with LN by renal biopsy were selected for retrospective study.According to Semi-quantitative score of LN activity and chronic disease≥ 12 points,they were divided into 37 cases in the inactive group and 43 cases in the active group;In addition,20 patients who underwent nephrectomy due to renal trauma were included as the control group.Collect the clinical indicators and laboratory test results of all the subjects,Observe the damage of glomerulus and podocyte via light microscope(HE,PAS,Masson staining),electron microscope;Immunohistochemical staining method was used to determine the specific markers of podocyte Nephrin,the expression level of Sirt6 in kidney tissue and the degree of macrophage infiltration;and immunofluorescence method was used to determine the position of Sirt6 and infiltration of macrophages phenotypes(CD206/CD68,i NOS/CD68),and the correlation was calculated.Results:(1)Compared with the control group,24-hour urine protein quantification,cholesterol,triglycerides,creatinine,urea nitrogen,uric acid,c-reactive protein,erythrocyte sedimentation rate in LN patients increased,while hemoglobin,platelets,albumin,complement C3,complement C4,estimated glomerular filtration rate decreased,the above changes in the LN activity group were more obvious,and the differences were statistically significant(P<0.05).(2)Compared with the control group,the expression of Nephrin in the kidney tissue of LN patients decreased,the CD68 infiltration of macrophages increased,and the expression level of Nephrin was negatively correlated with the infiltration degree of CD68 macrophages(r=-0.961,P<0.01).(3)The infiltration of macrophages in the kidney tissue of LN patients is mainly M2 type,and the degree of infiltration is negatively correlated with the expression of Nephrin(r=-0.853,P<0.01).(4)The expression level of Sirt6 decreased in the kidney tissue of LN patients,which is more more obvious in the LN-IV than the LN-III,LN-V,and LN-V+III types(P<0.05).The expression level of Sirt6 was positively correlated with 24-hour urine protein quantification(r=-0.648,P<0.01),while positively correlated with serum albumin(r=0.653,P<0.01)and complement C3(r=0.513,P<0.01).(5)The expression level of Sirt6 was positively correlated with the expression level of Nephrin(r=0.908,P<0.01),and negatively correlated with the infiltration degree of macrophage in kidney tissue(r=-0.961,P<0.01).(6)The expression level of Sirt6 in kidney tissue was negatively correlated with the infiltration degree of macrophage M1(r=-0.607,P<0.01),and M2(r=-0.904,P<0.01).Conclusion: This study found that there is podocyte damage in patients with lupus nephritis,and the decrease of Sirt6 expression is related to podocyte injury.The mechanism of participating in podocyte injury may be that by Sirt6 regulates the macrophage phenotype change in kidney tissue of LN patients.