The Role Of Th17 Cell In The Nervous System Injury Following Lead Exposure In Obesity Mice

Objective: To explore the effect of Th17 cells on the nervous system injury in obesity mice induced following lead exposure,the model of obesity mice with lead exposure were established,the impairment of subventricular zone in obesity mice after lead exposure were detected,and the number of Th17 cells and the expression of IL-17 in SVZ of obesity mice after lead exposure were detected,Methods: A total of 60 healthy C57 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 combine with lead exposure group.Tthe mice in lead exposure group and obesity combine with lead exposure group were given 250mg/L lead acetate by free drinking water for 9 weeks,while the mice in control group and obesity group were free drinking purified water.Morris water maze was used to detect the spatial learning and memory ability of mice,open field experiment was used to detect the behavior of autonomous exploration in mice.The contents of lead in the whole blood and SVZ of the mice were detected by ICP-MS.The expression of BDNF in SVZ was detected by Western blot.The the number of newborn neurons and the number Th17 cells in SVZ/choroid plexuswere observed by immunofluorescence.The percentage of Th17 cells in blood was detected by flow cytometry.The content of IL-17 in SVZ was detected by ELISA kit.And real-time PCR was applied to detect the m RNA expression of VCAM-1,ICAM-1,CCL20 in CP.Results 1 After three months high fat feed,the weight of mice in high fat diet group was 20% more than that of normal diet group.2 After 9 weeks lead exposure,compared with the control group,the escape latency in mice of obesity group and lead exposure group increased,and the frequency of passing platform decreased(P<0.05).In particular,compared with obesity group and lead exposure group,the escape latency in the third day of the obesity combine with lead exposure group were increased;Compared with the control group,the time of staying at the central region,the number of traversing the lattices,and the path in the central region in obesity group and lead exposure group were all reduced(P<0.05),and these in the obesity combine with lead exposure group were significantly decreased compared with obesity group and lead exposure group(P<0.05).3 Compared with the control group and the obesity group,the lead content of whole blood and SVZ were increased in the lead exposure group and the obesity combine with lead exposure group mice(P<0.05).4 Compared with the control group,the BDNF expression in SVZ of mice in obesity group and lead exposure group were decreased(P<0.05),BDNF expression in the obesity combine with lead exposure group was lower than the obesity group and lead exposure group respectively.5 The number of newborn neurons in SVZ of mice in the obesity group and lead exposure group decreased as compared with the control group.And the number of newborn neurons in the obesity combine with lead exposure group was only 20.1% and 25.1% of that in obesity group mice and lead exposure group mice.6 The number of Th17 cells of SVZ in the obesity group mice and lead exposure group mice were higher than that in control grouop,and the number of Th17 cells of SVZ in obesity combine with lead exposure group mice were 2.5 folds and 2.1 folds than that in the obesity group and lead exposure group(P<0.05).7 Compared with control group [(22.51±3.57)?g/g prot],the expression of IL-17 of SVZ in obesity group mice [(27.97±6.57)?g/g prot] and lead exposure group mice [(33.45±8.16)?g/g prot] were increased significantly(P<0.05),and that in obesity combine with lead exposure group [(41.23±9.73)?g/g prot] was higher than that in the obesity group and lead exposure group(P<0.05).8 The detection of Th17 in blood were found that compared with the control group,the percentage of Th17 cells in obesity group and lead exposure group were increased(P<0.05);And the percentage of Th17 in obesity combine with lead exposure group were 1.4 and 1.7 folds than that in the obesity group and lead exposure group(P<0.05).9 In CP,numbers of Th17 cells in the obesity group and lead exposure group were higher than that in control group,and more Th17 cells were found in besity combine with lead exposure group than that in the obesity group and lead exposure group(P<0.05).10 Compared with the control group,the m RNA level of CCL20 in CP was higher than that in the obesity group and lead exposure group(P<0.05),and that in the obesity combine with lead exposure group were higher than that in obesity group and lead exposure group(P<0.05).11 In CP,compared with the control group,the m RNA levels of VCAM-1 and ICAM-1 in the obesity group and lead exposure group were significantly rised,and compared with the obesity group and lead exposure group,the expression of VCAM-1 m RNA in the obesity combine with lead exposure group increased significantly(P<0.05),but there was no significant difference in ICAM-1 m RNA expression among obesity group,lead exposure group and the obesity combine with lead exposure group(P>0.05).Conclusions Lead exposure could enhance the Th17 translocation through choroid plexus from the peripheral blood to the subventricular zone in the obesity mice.Then Th17 cells secreted IL-17 increasedly,thereby reducing the expression of BDNF,damaging the regeneration of neurons in SVZ,resulting in further decline in neurobehavioral dysfunction.