Correlation Of Wnt/β-catenin Signaling Pathway In Cognitive Dysfunction In Chronic Renal Disease

Objective To explore the correlation between Wnt/β-catenin signaling pathway and Cognitive Impairment in chronic kidney disease.method clean grade healthy female C57BL/6 mice,aged 5 months,weight 20-25 g,were randomly divided into two groups :control group(Ctrl group)and cisplatin treatment group(CKD group).The CKD group was injected with cisplatin twice at an interval of 2 weeks.(1)Masson staining was used to observe renal lesions in mice.HE staining was conducted to observe the pathological changes of kidney.(2)At the end of the 8th week after the first injection,The water maze experiment was conducted to observe whether the mice had cognitive impairment.The mice were sacrificed and their serum,kidney,frontal lobe and hippocampus were collected.(3)HE staining was conducted to observe the frontal lobe and hippocampus.(4)The expression levels of Wnt4、 β-catenin and DKK1 in the kidney,frontal lobe and hippocampus of mice were detected by immunofluorescence assay.(5)The expression levels of Wnt4、β-catenin and DKK1 in blood samples were determined by ELLSA.(6)m RNA expression levels of Wnt4 and β-catenin in kidney,frontal lobe and hippocampus of experimental mice were detected by RT-PCR.(7)Western Blot was used to detect the expression levels of Wnt4,β-catenin and DKK1 in the kidney、frontal lobe and hippocampus of mice.Results(1)Masson staining of kidney tissue(glomeruli、tubules)was observed in CKD group with unclear structure.There is a high degree of fibrosis throughout the renal field,mainly concentrated in the glomerulus and the lumen of the renal tubules in the medulla.The boundary between the cutaneous and medulla of kidney tissue was not clear in CKD group.The glomerulus of the entire renal field was significantly reduced,and the renal structure could not be distinguished.(2)In the water maze test,a longer escape latency was observed in mice in the CKD group compared with the Ctrl group.(3)In the CKD group,the structure and hierarchy of the prefrontal cortex were unclear,the number of cells was significantly reduced,the nucleolus was swollen and decomposed,and the neurocytosis in the right prefrontal tissue was the most serious,with pathologically like vacuolar structures and clusters of inflammatory cells.The cells in the hippocampus of CKD group showed severe swelling,chromatin swelling and even decomposition.(4)Immunofluorescence showed that Wnt and β-catenin protein aggregated in and around the nucleus in kidney of CKD group.The two proteins showed a sudden increase of aggregation.Wnt and β-catenin proteins were pairwise close to each other.In the frontal lobe of CKD group,Wnt4 and β-catenin proteins were uniformly distributed around the nucleus.There were two proteins close to each other,but the fluorescence intensity was not high,and there was no sharp increase in the aggregation of two proteins.(5)ELLSA assay showed that the expression levels of Wnt4、 β-catenin and DKK1 were significantly up-regulated in the blood of mice in CKD group.(6)RT-PCR showed that the m RNA expression levels of Wnt4 and β-catenin were increased in kidney tissues of mice in the CKD group,while the m RNA expression levels of Wnt4 and β-catenin in frontal tissues hippocampus of mice in the CKD group were decreased.(7)Western Blot showed that the expression levels of Wnt4 and β-catenin in kidney tissues of mice in CKD group were increased,while the expression level of DKK1 was decreased.The expression levels of Wnt4 and β-catenin in the frontal lobes hippocampus of mice in CKD group were decreased,while the expression level of DKK1 was increased.Conclusion(1)Compared with the Ctrl group,CKD mice showed cognitive impairmen.(2)CKD mice showed damage to the frontal lobe and hippocampus(3)In the CKD group,the Wnt/β-catenin signaling pathway was activated in the kidney tissue and inactivated in the frontal lobe.