摘要Objective:Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early-and late-stage CKD models in Sprague-Dawley rats.Methods:The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery.Histopathologic examinations were conducted to examine renal and hippocampal damage.Real-time PCR,Western blotting analysis,and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor(BDNF),choline acetyltransferase(ChAT),and synaptophysin(SYP).Results:Compared with the control rats,the rats with early-stage CKD exhibited mild renal damage,while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage.The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats,with further deterioration observed in the rats with late-stage CKD.Additionally,we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD,which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD.Conclusion:These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly.In addition,the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.