| Objective A chemical solvent commonly used in modern industries,chiefly in footwear,printing,painting,and electronics.Due to the low acute toxicity of n-hexane,cases of n-hexane acute poisoning are rare in occupational work.Occupational n-hexane poisoning is mainly caused by long-term low dose exposure to n-hexane chronic poisoning,n-hexane chronic poisoning mainly involves the peripheral nerves,the main clinical symptoms of multiple peripheral neuropathy.At present,there are many studies on the effect biomarkers of n-hexane,most of which focus on 2,5-hexanedione,pyrrole adducts,blood shadow proteins,neurocytoskeleton proteins,etc.However,these indicators have some defects and cannot be used as ideal biomarkers for n-hexane early exposure effect.N-hexane mainly causes axonal damage,while neurofilament protein is an important component of axonal and plays a key role in axonal transport.Neuron-specific enolase is involved in the energy required for axoplasmic transport.Lack of nerve growth factor can lead to the apoptosis of neurons,resulting in the death of nerve cellsand atrophy of axons.Therefore,this study intends to detect changes in serum levels of neuron-specific enolase,neurofilament protein and nerve growth factor as well as changes in gene expression levels of the above indicators in spinal cord and sciatic nerve tissues from the perspective of animals,so as to explore their potential as biomarkers of n-hexane early exposure effect.From the perspective of occupational population,the change level of the above indicators and the change relationship of NCV in serum were tested to prove this.Method1.Twenty-four eight-week-old SD male rats were selected and randomly divided into 4 groups according to their body weight after passing quarantine,with 6 rats in each group.Group 1: blank control group;Group 2: n-hexane low dose group;Group 3: n-hexane medium dose group;Group 4: n-hexane high-dose group.The doses of n-hexane were168mg/Kg,675mg/Kg and 2700mg/Kg,respectively.Each group was administrated by gavage according to 10mg/Kg body weight and infected for 6 weeks,5d/ week.At week 0,2,4 and 6,1.5ml of blood was collected from inner canthus to determine the contents of NSE,NF-L and NGF in serum.After the poisoning,the rats were sacrificed,the spinal cord and sciatic nerve of the rats were dissected and removed to determine the activities of superoxide dismutase(SOD),glutathione 9peroxidase(GSH-px)and lipid peroxidase malondialdehyde(MDA)in the tissues,and the mRNA expression levels of NSE,NF-L and NGF were determined by RT-PCR.2.73 workers from a factory with chronic n-hexane poisoning in dongguan city in 2016 were selected for adjustment to collect the length of service and serum of the patients exposed to n-hexane,and conduct neuroemg examination of the patients to analyze the change level of relevant indicators in the patients' serum and the performance characteristics of the neuroemg.Results1.Poisoning results of rats: during the experiment,all rats in each group died.Compared with the control group,the low-dose and medium-dose rats showed slow body mass growth at week 6,while the high-dose rats showed slow body mass growth at week 2 and negative body mass growth at week 6.The body mass of the rats was statistically significant in the interaction between the infection treatment group and the infection time(P<0.05).2.Results of gait score of rats: at week 0,the gait of rats in the three dose groups was normal.At week 2 and 4,no abnormal gait was found in the low-dose and medium-dose rats,while 1 and 2 rats in the high-dose group showed mild abnormal gait.At the 6th week of infection,3 rats inthe low-dose group presented mild gait abnormalities,but none presented moderate or severe gait abnormalities.In the medium dose group,4 rats presented mild abnormal gait,2 rats presented moderate abnormal gait,but no severe abnormal gait.In the high-dose group,2 rats presented moderate gait abnormalities,and 4(70%)rats presented severe gait abnormalities.The gait score of rats had statistical significance in the main effect and the interaction effect of infection treatment and infection time(P<0.05).3.The levels of NSE,NF-L and NGF in the serum of rats were statistically significant in the interaction between infection treatment and infection time(P<0.05).The level of NGF in the serum of rats was only statistically significant in terms of the main effect of infection treatment and infection time(P<0.05).4.After 6 weeks of exposure,the activities of antioxidant enzymes SOD and gsh-px in the spinal cord and sciatic nerve tissues of rats decreased significantly in the low,medium and high dose groups(P<0.05),and the content of MDA,an intermediate product of lipid peroxidation,increased significantly in the low,medium and high dose groups(P<0.05).5.After 6 weeks of exposure,the expression levels of NSE and NF-L mRNA in the spinal cord and sciatic nerve tissues weresignificantly decreased in the low,medium and high dose groups(P<0.05).The expression level of NGF mRNA in spinal cord tissues was significantly down-regulated in the medium and high dose groups(P<0.05),and the expression level of NGF mRNA in sciatic nerve tissues was significantly down-regulated in the low,medium and high dose groups(P<0.05).6.The serum NSE level of occupational workers increased significantly in the occupational workers exposed to n-hexane for 1-3months,6-9 months and more than 12 months(P<0.05),and the serum nf-l level did not change significantly.7.MNCV of median nerve and sural nerve significantly slowed down in occupational workers exposed to n-hexane from June to September and ?12 months(P<0.05).In the occupational workers exposed to n-hexane from June to September and ?12 months,median nerve SNCV velocity was significantly reduced(P<0.05),while sural nerve SNCV velocity was significantly reduced in the occupational workers exposed to n-hexane ?12 months(P<0.05).Conclusion1.Under certain dose conditions,n-hexane can cause damage to peripheral nerve tissues and neuropathic changes in rats,and causeimbalance of oxidation/antioxidant system in rats,leading to oxidative stress.2.Under the effect of n-hexane neurotoxicity,the changes of rat serum level of NSE and NF-L relation with rats neurobehavioral changes were positively correlated,rats neurobehavioral changes in serum levels of NGF plays with rats are negatively related to change of the serum NSE and NF-L has the highest sensitivity,change of serum NSE levels than neuroethology changes appear earlier,a large range change,with hexane as the possibility of early exposure effect biomarkers.3.Under the present experimental conditions,the caritas of sciatic nerve tissue on n-hexane nerve toxicity may be higher than that of rat spinal cord tissue.4.Changes in serum NSE level in occupational workers were negatively correlated with changes in median nerve,sural nerve MNCV and sural nerve SNCV,and changes in serum NF-L level were only negatively correlated with changes in median nerve MNCV and SNCV,among which changes in serum NSE level were significantly correlated with changes in nerve conduction velocity.5.Through animal experiments and occupational population experiments,serum NSE level changes can be used as biomarkers of n-hexane early exposure effect. |
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