| Objective:To observe the effect of arsenic poisoning on the learning and memory ability of rats,and the effect of dictyophora polysaccharide on arsenic toxicity after intervention.Through the detection of arsenic content in hippocampus and blood of rats and proteomics research,the neurotoxic effect and mechanism of arsenic and the action mechanism of dictyophora polysaccharide on arsenic neurotoxicity were clarified,so as to provide a scientific basis for understanding the neurotoxicity of arsenic.Methods:Sixty SD rats,clean grade,were randomly divided into normal control group(20rats fed with ordinary feed),arsenic exposure group(20 rats fed with feed with arsenic content of 50 mg / kg)and dictyophora polysaccharide intervention group(arsenic + dictyophora polysaccharide)(20 rats fed with feed with arsenic content of50 mg / kg),half male and half female.After 3 months of exposure,the changes of body weight and morphology of the two groups were observed.Then,the normal control group was fed with ordinary feed and gavage with distilled water,the arsenic exposed group was fed with arsenic feed and gavage with distilled water,and the dictyophora polysaccharide intervention group was fed with arsenic feed and gavage with dictyophora polysaccharide solution.The concentration of dictyophora polysaccharide solution was 10 ml / kg.Rats in each group were gavaged with distilled water or dictyophora polysaccharide solution according to their body weight(20ml /kg.BW).After one month,morris water maze test was used to evaluate the learning and memory ability of rats;The contents of arsenic in hippocampus and blood were measured by ICP-MS;Nissl staining was used to observe the changes of hippocampal neurons and Nissl bodies;proteomic method was used to observe the changes in hippocampal protein levels in rats,and the differential proteins were analyzed by bioinformatics;The differential protein expression was verified by Western blot.Results:The results of morris water maze experiment showed that compared with the control group and intervention group,the swimming trajectory line of arsenic exposed rats was more irregular,the escape latency was higher,the time of crossing the target platform and the time of target quadrant were less,and the difference was statistically significant(P < 0.05).The detection of arsenic content showed that the blood arsenic and hippocampal arsenic content in the arsenic exposure group and the dictyophora polysaccharide intervention group were significantly higher than those in the control group,and the difference was statistically significant(P<0.05).Hippocampal Nissl staining showed that the neurons in hippocampal CA1 and CA3 areas of arsenic exposed rats were sparse and disordered,and the area of neurons was significantly reduced.The neurons in DG,CA1 and CA3 areas of dictyophora polysaccharide intervention group and control group were large,full and arranged in close order.Proteomic analysis showed that most of the differential proteins enriched in energy metabolism,apoptosis,synapses,neurons and mitochondria in the arsenic poisoned hippocampus were dysregulated,and the expression levels of these proteins were restored after dictyophora polysaccharide intervention.Western blot results showed that compared with the control group,Lrp1 and Hsp90aa1,two key proteins enriched in catabolism,neurons and mitochondria,were down-regulated in the arsenic exposure group,and the difference was statistically significant(P<0.05).Compared with the arsenic exposure group,the expressions of Lrp1 and Hsp90aa1 were also up-regulated in the dictyophora polysaccharide intervention group,and the difference was statistically significant(P<0.05).Conclusions:After arsenic poisoning in rats,arsenic ions can cross the blood-brain barrier and enrich in the hippocampus,leading to spatial learning and memory dysfunction and pathological damage in the hippocampus of rats.The supplementation of dictyophora polysaccharide can improve the neurotoxicity of arsenic poisoning.The results of proteomics also showed that arsenic was neurotoxic,which could lead to the down-regulation of energy metabolism,mitochondria,synapses and neuron related proteins in most hippocampus,and the up-regulation of apoptosis related proteins.Dictyophora polysaccharide had certain intervention and protective effects on arsenic neurotoxicity.These findings may provide a direction for the study of dictyophora polysaccharide to improve arsenic neurotoxicity.We still need to more studies and further verify the molecular mechanism of arsenic induced hippocampal toxicity and the hypothesis proposed of this study in futute. |
