Effect of Astragalus fermentation on hippocampal damage and learning and memory impairment in iodine-deficient rats by regulating Fas signaling pathway
Objective To explore the effect of Astragali radix fermentation on hippocampal damage and learing and memory function in iodine-deficient rats by regulating fatty acid synthetase(Fas)signaling pathway,in or-der to select its best preparation.Methods Sixty Wistar rats were randomly divided into a normal control group,model control group,4.00,2.00,1.00 g·kg-1 group,and positive drug(levothyroxine sodium 9×10-3 mg·kg-1)group.Except for the normal control group,rats were fed an iodine-deficient diet(iodine content of about 20 μg·kg-1)for 90 days to replicate an iodine-deficient model.The levels of free triiodothyronine,free tetraiodo-thyronine and thyroid stimulating hormone in the serum of each groupwere tested and they showed successful modeling.The learning and memory levels were tested by the platform and Morris water maze;the activities of choline acetyltransferase,acetylcholinesterase,catalase and the contents of acetylcholine and malondial-dehyde in serum were detected by enzymoly-linked immunosorbent assay.The survival time and brain index after hypoxia were observed.Hematoxylin-eosinand terminal deoxynucleotide transferase mediated dUTP notch end labeling(TUNEL)staining were used to observe the histopathological changes in hippocampus.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression of Fas,Caspase-3,B lymphoblastoma-2 gene(Bcl-2)and Bcl-2 associated X protein(Bax);and the expressions of Fas,Caspase-3,Bax and Bcl-2 proteins were detected by Western Blotting.Results Compared with the normal group,the model rats underwent a significant decrease in learning and memory ability,a decrease in Ach level and antioxidant vitality in brain tissue,different degrees of damage and apoptosis,disordered arrangement of nerve cells,an increased expression of Fas,Caspase-3,Bax genes and protein,and decreased expression of Bcl-2.Compared with the model group,the latency and number of errors in Morris water maze,the percentage of residence time in the target quadrant and the number of platform crossings were increased;activities of choline acetyltransferase,catalase viability and acetylcholine content,acetylcholines-terase vitality and malondialdehyde content decreased;prolonged survival time after hypoxia,and brain index increased;the histopathological damage of the hippocampus was significantly improved;the relative expres-sion levels of Fas,Caspase-3,and Bax mRNA were reduced,the expression level of Bcl-2 increased and the Bax/Bcl-2 decreased;the relative expression levels of Fas,Caspase-3 and Bax proteins were also significantly decreased while the Bcl-2 protein was increased.The results were related to the doses given.Conclusion Astrag-alus fermentation can improve the learning and memory dysfunction in iodine-deficient rats,and the mecha-nism may be related to the inhibition of Fas signaling pathway and the regulation of acetylcholine metabolism,thus improving energy metabolism and alleviating oxidative stress damage and inhibition of apoptotic effects.
astragali radix fermentationlodine deficiencyfatty acid synthetasehippocampuslearning and memoryapoptosis
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