Correlation Analysis Of Renal Macrophage BTK Expression And Clinical Indicators In Patients With Diabetic Nephropathy

Background and purpose: DN is one of the main chronic complications of diabetes and has gradually become the main cause of ESRD.The pathogenesis of DN is complex,in which inflammation and fibrosis both play an important role in the occurrence and development of the disease.Current studies have found that a high-glucose environment can induce a variety of inflammatory cells(including T cells,mast cells,macrophages,etc.)to activate and infiltrate the kidneys,mainly macrophages.Macrophages can aggravate kidney damage through a variety of ways,and promote inflammation and fibrosis of the kidney.BTK is a non-receptor tyrosine kinase of the Tec family,which is mainly expressed in myeloid hematopoietic cells.In addition to its important role in regulating B cells,BTK can also regulate the activation of macrophages and the release of pro-inflammatory mediators through the Toll-like receptor signaling pathway,thereby affecting the progression of DN.The previous research of the research group confirmed that the high glucose environment can activate the expression of BTK in bone marrow-derived macrophages,and by activating the downstream NF-κB signaling pathway,thereby inducing the release of pro-inflammatory mediators,and BTK inhibition can alleviate this process.BTK The role in clinical DN has not yet been elucidated.Therefore,this study intends to use human specimens to explore the correlation between BTK expression of macrophages and clinical indicators.Method: 18 cases of normal volunteers and 18 cases of normal kidney tissue adjacent to cancer were collected as the Control group.A total of 49 patients with DN who were hospitalized in the First Affiliated Hospital of Anhui Medical University from January 2016 to January 2020 and were diagnosed with DN by renal biopsy were collected,and their serum and kidney tissue were collected.At the same time,general clinical data and biochemical indicators of subjects were collected,including gender,age,glycosylated hemoglobin,BMI,SBP,DBP,MAP,24-hour urine protein,serum creatinine,blood urea nitrogen,e GFR,and blood uric acid.ELISA was used to detect the expression of inflammatory factors IL-1β,TNF-α and MCP-1 in the serum of each group;immunohistochemistry was used to detect the expression changes of TNF-α,IL-1β,CD68,BTK and p-BTK in the kidney tissue of each group;laser;Confocal detection of macrophages co-labeled expression with i NOS,BTK and p-BTK in kidney tissues of each group.Result: Compared with the Control group,patients in the DN group had a significant increase in glycosylated hemoglobin,SBP,DBP,MAP,24-hour urine protein,serum creatinine,blood urea nitrogen,and blood uric acid,and a significant decrease in e GFR.There was no statistical difference in BMI.The ELISA results showed that compared with the Control group,the inflammatory factors TNF-α,IL-1β,and MCP-1 in the serum of the DN group were significantly increased,suggesting an increase in inflammatory mediators in the serum of DN patients.The results of immunohistochemistry showed that the expression of TNF-α and IL-1β in the kidney of the DN group was significantly higher than that in the Control group,suggesting that inflammation in the kidney tissue of DN patients,CD68 and BTK also increased in the glomeruli and tubular interstitium of the DN group.The expressions of BTK and p-BTK were significantly increased,suggesting that the infiltration of macrophages in the renal tissues of patients with DN was increased,accompanied by increased expression and phosphorylation of BTK.The laser confocal results showed that compared with the Control group,the macrophage infiltration in the kidney of the DN group increased,and the expression of i NOS,BTK,and p-BTK in the macrophages increased,indicating that the macrophages in the kidneys of patients with DN were activated and accompanied by activation and phosphorylation of BTK.The results of linear correlation analysis showed that the expression of BTK in glomeruli in the DN group was positively correlated with urine protein and serum creatinine,and negatively correlated with e GFR.At the same time,BTK expression in the renal tubule interstitium was also positively correlated with urine protein and serum creatinine,which was also negatively correlated with e GFR,which suggests that the activation of BTK in the kidney of DN patients has a strong correlation with clinical indicators.Conclusion: The inflammation in the serum and kidney of DN patients increased,and the infiltration and activation of macrophages and BTK in the kidney increased.The expression of BTK has an important correlation with the clinical indicators of DN patients.BTK can be used as a potential target for the treatment of DN.