To investigate the mechanism of imperatorin on Aβ1-42 induced neuronal damoge in Alzheimer's disease model mice based on X-linked inhibitor of apoptosis protein/Smac/DIABLO pathway

LUO Li; WAN Hangjuan; HE Wei

Abstract：Objective:This study aimed to explore the mechanism by which imperatorin(IMP)modulates neuronal apoptosis in Alzheimer's disease(AD)induced by β-amyloid1-42(Aβ1-42),focusing on X-linked inhibitor of apop-tosis protein(XIAP)/the second mitochondrial-derived activator of caspases(Smac/DIABLO)signaling pathway.Methods:An in vitro model of AD was established by treating isolated mouse brain slices with three different concen-trations of Aβ1-42(1μmol/L,10μmol/L,and 20μmol/L).Degree of cellular damage was assessed by detecting the ac-tivities of lactate dehydrogenase(LDH),Caspase-3,and Caspase-9,and protein levels of XIAP and Smac/DIABLO were determined by enzyme-linked immunosorbent assay(ELISA).Additionally,AD mouse models were constructed and treated with IMP(2.5 mg·kg-1·d-1,5.0 mg·kg-1·d-1)for 13 days.After treatment,the cerebral cortex was stained with Nysted to observe the neuronal status,and Western blot was used to detect changes in XIAP/Smac/DIAB-LO pathway-related proteins.Results:In vitro experiments showed that the Smac/DIABLO protein content and LDH,Caspase-3 and Caspase-9 activities were significantly elevated in each Aβ1-42-treatedgroup compared with the con-trol group,while the XIAP protein content was decreased,and the difference was also statically significant(P<0.05).In AD model mice,Nysted staining showed a significant increase in neuronal damage,with up-regulated expression of Smac/DIABLO and its downstream effector proteins,and down-regulated XIAP protein levels,and the difference was also statically significant(P<0.05).Compared with the AD mouse group,neuronal injury was alleviated in the IMP-treated group,the expression of Smac/DIABLO and its downstream effector proteins was decreased,and the XIAP protein level was increased,and the difference was also statically significant(P<0.05).Conclusion:IMP can effectively alleviate neuronal damage in AD mice by inhibiting Smac/DIABLO expression and promoting XIAP expression.