| Objectives In the study,mice was applied to preliminarily clarify the effects of lead exposure on neuroinflammation and Th17 cells in obesity mice.the factors regulating Th17 cells across the choroid plexus were investigated.Our finding will provide the basis for the mechanism of central nervous system injury induced by lead exposure.Methods 1 60 healthy C57/BL/6 male mice were randomly divided into common diet group and high fat diet group.The criteria for obesity models established is that the weight of each mouse in the high fat diet group was more than 20% of the average weight of the common diet group.Then the mice in the common diet group were randomly divided into the control group and the lead exposure group.The mice in the high fat diet group were randomly divided into obesity group and obesity+lead exposure group.The mice in lead exposure group and obesity+lead exposure group were given 250 mg.L-1lead acetate by free drinking water,while the mice in control group and obesity group were free drinking purified water for 12 weeks.2 Morris water maze,new object recognition test and open field test were used to detect the behavioral changes of mice;3 The contents of TG and T-CHO in serum of mice were determined by colorimetry;4 The expression of IL-1?,Iba1,IL-17 A,IL-22,TNF-a,IL-6,TGF-? in mouse hippocampus and hypothalamus,and CCL21 in CP was detected by Western blotting;5 The proportion of Th17 cells in blood and brain was detected by Flow cytometry;6 CCK-8 kit was used to detect the effect of lead acetate and palmitic acid on the growth of Z310 cells;7 Z310 cells key chemokines was screened by antibody chip;8 Blood–CSF model was appled to verify the regulationg effect the chemokines CCL21 on Th17 cells.Results 1 The results of water maze showed that the escape latency of obesity+lead exposure group was higher than that of obesity and lead exposure group alone?P < 0.05?;In the open field experiment and new object recognition results,the number of standing times and new object recognition index of obesity+lead exposed mice decreased significantly,which was lower than that of obesity or lead exposed group alone?P < 0.05?.2 The expression of IL-1? in the hippocampus of obesity group and lead exposed group was 1.67 and 1.69 times higher than that of the control group?P < 0.05?,obesity + lead exposure group was higher than obesity group and lead exposure group?P < 0.05?;The expression of Iba1 in the hippocampus of obesity group and lead exposed group was higher than that of obesity group and lead exposure group?P < 0.05?;Compared with the control group,the levels of IL-6,TGF-?,IL-1 ? and TNF-a in the hypothalamus of obesity and lead exposed mice increased,the expression of IL-1?,IL-6 and TGF-? in the hypothalamus of obesity+lead exposed mice were higher than those of the obesity and lead exposed mice,the expression of TNF-a protein in hypothalamus of obesity+lead exposed mice was higher than that of obesity group?P < 0.05?;3 The percentage of Th17/CD4+ T cells in the obesity group and the lead exposed group higher than in the control group,the obesity+lead exposed group higher than that of obesity or lead alone exposed group;Compared with the control group,the expression of IL-17 A and IL-22 in the hippocampus and hypothalamus of obesity group and lead exposed group increased,and the expression of IL-17 A in obesity + lead exposed group was higher than in obesity group and lead exposed group?P < 0.05?.The percentage of Th17/CD4+ in blood of obesity+lead exposure group was higher than that of obesity and lead exposure group?P < 0.05?.4 The chemokines CCL21,28,27,8,6,3/4,CXCL16,13 and IL-16 of T-lymphocytes were significantly higher than those of lead acetate and palmitic acid alone,CCL21 increased the most significantly.5 Compared with the obesity group and the lead exposure group,the expression of CCL21 in the CP of obesity+lead exposure group increased by 2.55 and 1.37 times that of the obesity group and lead exposure group.6 After CCL21 decreased,the number of Th17 cells in the lead and palmitic acid exposed group decreased significantly?P < 0.05?.Conclusions Lead exposure can aggravate the injury of neuroinflammation in obesity mice,which is manifested by the increase of Th17 cells and the release of IL-17 A.Furthermore,CCL21 in the blood cerebrospinal fluid barrier regulating Th17 cells entering the central nervous system was involved in this process.Figure 15;Table 9;Reference 137... |
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