Correlation Between Fe Metabolism And TCM Syndromes In The Elderly With Mild Cognitive Impairment And The Study Of Fe₃O₄ Nanoenzyme Promoting Neuroblasts Differentiation

Part ?Correlation Between Fe Metabolism and Mild Cognitive Impairment&TCM Syndrome Types in the ElderlyObjective:The objective of the study is to investigate the correlation between Fe metabolism and mild cognitive impairment&TCM syndromes in the elderlyMethods:According to the inclusion and exclusion criteria,150 patients were finally enrolled.There were 108 patients in mild cognitive impairment group and 42 patients in normal control group.It was firstly to find differences in age,gender,years of education and other factors between two groups.The biochemical indicator and Fe metabolism related indicators were measured in the study.Then the correlation between each factor and cognitive function were analyzed.What's more,patients with cognitive dysfunction were classified according to TCM syndrome types and the correlation between different TCM syndrome types and Fe metabolism indicators were analyzed.Results:1.There were significant differences in age,years of education and low-density lipoprotein between MCI and NC groups.Compared with normal control group,patients in MCI group were older and had shorter years of education and higher level of low-density lipoprotein(p<0.05).There were no significant differences in history of alcohol intake,smoking history,whether living alone,diabetes,history of hypertension,BMI and BADL scores(p>0.05).2.The levels of hemoglobin,serum iron and soluble transferrin receptor in the mild cognitive impairment group were lower than these in the normal control group(p<0.05),however,serum hepcidin levels were higher than these in the normal control group.There were no significant differences in serum ferritin,transferrin and total iron binding capacity between two groups(p>0.05).3.Multiple linear regression analysis showed that years of education were positively correlated with the MoCA scores and hepcidin levels were negatively correlated with MoCA scores.4.The common syndrome types of elderly MCI patients were insufficient of qi and blood and deficiency of spleen and kidney.The most severe cognitive impairment and the highest syndrome scores were found in these two syndrome types.The hemoglobin and serum iron levels were lower than the other three syndrome types including the blood stasis blocking brain,hyperactivity of yang due to yin deficiency and fu-organ turbidness stagnation.However,the hepcidin level were higher than these three syndrome types.Conclusion:1.Age,years of education,high low-density lipoprotein levels,low hemoglobin,low serum iron levels,low soluble transferrin receptors,and high hepcidin levels are risk factors for mild cognitive impairment in the elderly.2.Years of education and hepcidin were most closely related to cognitive function and the years of education were positively correlated with the MoCA scores and hepcidin levels were negatively correlated with MoCA scores.Both of them could be used as potential markers to assess the severity of cognitive dysfunction.3.Insufficient of qi and blood and spleen and kidney deficiency syndromes were the dominant syndrome types of MCI in old people and were with the most severe cognitive impairment.In these two syndrome types,serum iron and hemoglobin level were significantly reduced and hepcidin levels were significantly increased.Part ?Study of Fe3O4 Nanoenzyme Promoting Neuroblasts Differentiation in the D-Galactose-Induced Aging MiceObjective:To explore the effect of Fe3O4 nanoenzyme promoting the neuroblasts differentiation in the D-galactose-induced aging mice.Methods:Seventy male ICR mice were randomly divided into five groups:control group,100mg/kg D-gal treatment group(D-gal group),10 ?g/ml PEG-Fe3O4 nanoenzyme treatment group(pFe3O4 group),10?g/ml PEG-Fe3O4 nanoenzyme+100mg/kg D-gal treatment group(pFe3O4+D-gal group),50 mg/kg Melatonin+100mg/kg D-gal group(Mel-gal group).Except for the control group and pFe3O4 group,mice in the other groups were intraperitoneally injected with D-galactose 100 mg/kg daily for 12 weeks.From the ninth week,melatonin was administrated by gavage once a day at 50 mg/kg body weight for 4 weeks in Mel-gal group,Fe3O4 nanoenzyme was drunk daily(diluted with normal saline at 10?g/ml)for 4 weeks in pFe3O4+D-gal group and pFe3O4 group.Inductive Coupled Plasma Emission Spectrometer was used to determine the iron content in the brain;immunohistochemistry was used to determine the neural differentiation,glial cell activation and vascular endothelial cell changes in the dentate gyrus of hippocampus;Western blot analysis was performed on the expression of antioxidant enzyme related proteins,tight junction proteins,apoptosis and autophagy-related proteins.Results:1.Fe3O4 nanoenzyme significantly increased the number of doublecortin(DCX)positive neuroblasts in the dentate gyrus of hippocampus in aging mice.2.Fe3O4 nanoenzyme significantly increased the antioxidant protein levels including SOD-1/2 and Catalase in the hippocampus of aging mice.3.Fe3O4 nanoenzyme significantly inhibited the activation of astrocytes and microglia in the hippocampus of aging mice.4.Fe3O4 nanoenzyme maintained the integrity of the blood-brain barrier,activated autophagy and reduced the expression of apoptosis-related proteins in the hippocampus of aging mice.Conclusion:Fe3O4 nanoenzyme could exert its antioxidant activity and promoted the neuroblasts differentiation in hippocampal dentate gyrus in aging mice through anti-glial,maintaining blood-brain barrier integrity,activating autophagy and anti-apoptosis.