Role Of Th17/Treg Cytokines In Nerve Injury In Obese Population Following Lead Exposure

ObjectiveThe current study is aimed to investigate the relationship between serum Th17/Treg cytokines and neurobehavioral impairment of obesity workers following lead exposure.Then,obese animal model exposed to lead was establishedto explore the changes of Th17/Treg cytokines in brain tissue and its correlation with serum indexes in order to elucidate the role of Th17/Treg cytokines in the aggravation of neurological injury in obese people exposed to lead.Our finding will provide a new basis for the prevention and control of neurological injury in the occupational population,especially in obese population,following lead exposure.Methods1 A total of 153 workers in a battery factory in Tangshan City were selected as lead exposure group,and 163 workers matched in sex and age who were not exposed to lead and other nervous system hazards were served as control group.All subjects were divided into normal control group,obese group,normal weight lead exposure group and obese weight lead exposure group based on BMI value.2 Self-made questionnaires was used to collect general information.Inductively coupled plasma mass spectrometry?ICP-MS?was applied to detect lead in blood.3 The core neurobehavioral test?WHO/NCTB?was used to detect the emotional state and neurobehavioral function of the subjects.Serum levels of IL-17A,IL-10,IL-22 and TGF-?were detected by ELISA.4 A total 48male Kunming mice with normal weight or obesity were randomly divided into control group,obesity group,lead exposure group,lead exposure+obesity group.Rats in Lead exposure group,lead exposure+obesity group were treated with 250mg/L lead acetate drinking water for 6 months.5 The histopathological changes of hippocampus in mice were observed by HE staining.6 Morris water maze,new object recognition,open field and elevated cross experiments were used to test the neurobehaviour of mice.7 The expression levels of IL-17A,IL-22,IL-10 and TGF-?in hippocampus of mice were detected by immunoblotting and ELISA.Results1.The effect of occupational lead exposure on blood lead content of obese people:Compared with the control group,the blood lead content of the lead exposure group increased?P<0.05?,and there is no significant difference between lead exposure+obesity group and lead exposure group.2.The influence of occupational lead exposure on the emotional state of obese people:Compared with the control group,the scores of strength-hyperactivity?V?decreased in obese group;The scores of tension-anxiety?T?,depression-depression?D?,anger-hostility?A?,fatigue-inertia?F?,confusion-confusion?C?increased in lead exposure+obesity group.The scores of T,D,A and F in lead exposure+obesity group were higher than those in lead exposure group and obesity group?P<0.05?.3.The effect of occupational lead exposure on neurobehavioral function of obese people:Compared with the control group,indices including the auditory digit span NAI,visual retention NAI,visual simple response NAI and NBI in the lead exposure group decreased?P<0.05?.The scores of auditory digital span NAI,visual retention NAI,visual simple response NAI and target tracking NAI in lead exposure+obesity group were all decreased than that in lead exposure or obesity group.Moreover,the NBI scores were also decreased in lead exposure+obesity group compared with lead exposure or obesity group.4.Serum IL-17A and IL-22 levels in obese people with lead exposure were higher than those in obese people or lead exposure?P<0.05?.Compared with the control group,the serum levels of IL-10 and TGF-?in lead exposure group were significantly lower.5.Serum Th17/Treg cytokine release level was positively correlated with emotional state and neurobehavioral NAI in obese people with lead exposure.Serum IL-17A level was positively correlated with emotional state indicators T,D,A and C scores,and negatively correlated with visual retention NAI,auditory digit span NAI and target tracking NAI;Serum IL-22 level was negatively correlated with NAI in visual simple response;Meanwhile,serum IL-10 level was negatively correlated with scores of T and A and positively correlated with NAI?r=0.242?;The serum TGF-?level was positively correlated with NAI of auditory digit breadth and NAI of target tracking.And The levels of IL-17A,IL-10 and TGF-beta were all correlated with NBI?r=0.003,r=0.001,r=0.036?.6.The effects of lead exposure on neurobehaviour of obese mice:1)Compared with the control group,the escape latency of obese group and lead exposed group was prolonged,and the escape latency of lead exposed+obese mice was higher than that of obese and lead exposed mice?P<0.05?.2)The time periods in the central area of the lead exposed group and lead exposed+obese group were less than that in the control group?P<0.05?.3)Compared with the control group and obesity group,the new object recognition index of the lead exposure group and the lead exposure+obesity group decreased?P<0.05?.4)The percentage of mice entering the open arm in obesity group and lead exposure group were lower than that in control group,and the percentage of time spent in lead exposure+obesity group was lower than that in control group?P<0.05?.7.The blood lead content of lead exposure group and lead exposure+obesity group was 2.24 and 2.27 folds higher than that of control group respectively.8.The effect of lead exposure on the expression of Th17/Treg cell release factor in the hippocampus of obese mice:Compared with the control group,the protein expressions of IL-17A and IL-22 in the hippocampus of the lead exposure group increased,while the expression of IL-10 and TGF-?decreased?P<0.05?;The levels of IL-17A and IL-22 in the serum of the lead exposure+obesity group were significantly higher than that of the obese group or lead exposure group,while the expression of IL-10 was lower.9.The effect of lead exposure on the level of Th17/Treg cell release factor in serum of obese mice:Compared with the control group,the levels of IL-10 and TGF-?in obese and lead-exposed mice decreased,and the levels of IL-17A and IL-22 in lead-exposed mice increased.The level of IL-17A in serum of mice exposed to lead plus obesity was higher than that of mice exposed to lead and obesity.The serum levels of IL-17A,IL-22,IL-10and TGF-?in the hippocampus of obese mice exposed to lead were positively correlated(r_IL-17A=0.004,r_IL-22=0.012,r_IL-10=0.001,r _TGF-?=0.015,P<0.05).ConclusionLead exposure can aggravate nerve impairment in obese population or obese mice,and the increase IL-17A in brain tissue and serum was also aggravated,which is related to neurobehavioral impairment.It is suggested that IL-17A is involved in the occurrence and development of neuroinflammation induced by lead exposure and it can be served as a candidate marker of nerve injury.Figure 8;Table 20;Reference 107...