Effects Of Lead On Glucose Metabolism In Rat Brain

[Objective]In order to enrich the theoretical study on the mechanism of brain damage caused by lead exposed and provide theoretical basis for the prevention of lead poisoning,this test explored the effects of different doses of lead on brain function of rats from the glucose metabolism.[Methods]In the test,40 healthy(55 ± 5)g male SD rats were adaptive fed for 7 days,and then were randomly divided into 4 groups:normal control group(deionized water + basal diet),low dose lead group(0.1%lead acetate deionized water solution + basal diet),middle dose lead group(0.2%lead acetate deionized water solution + basal diet),high dose exposure group(0.3%lead acetate deionized water solution + basal diet).During the test,the body weight of rats in each group were weighed every 5 days.After 65 days,the rat brain tissues were collected,and the hippocampus and cortex were isolated,then we determined the content of lead,calcium,zinc,iron,manganese,magnesium,copper and the enzyme activity of hexokinase(HK),fructose-6-phosphate kinase(PFK),pyruvate kinase(PK),6-phosphate glucose dehydrogenase(G-6-Pase);observed the apoptotic cells by TUNEL;determined the relative expression of Insr,Irs1,PI3K,Akt2,mTOR,GLUT-1 and GLUT-3 by RT-PCR,and the protein expression of GLUT-1 and GLUT-3 by Western-blot.[Results](1)Compared with the normal control group,body weight in dose group increased slowly,and it had dose-effect relationship.Before the 35th day,the body weight of low dose group was higher than that of the normal control group,the middle dose group and high dose group,respectively,reached a significant level on the 25th day and the 10th day(P<0.05),on the 55th day both groups were at the extreme level(P<0.01).(2)Compared with the normal control group,the content of Pb in the brain tissue of three dose groups significantly increased(P<0.05 or P<0.01),and had dose-effect relationship.The low dose group and middle dose group of calcium,zinc,iron,manganese,magnesium and copper content decreased,increased in high dose group.In the low dose group,magnesium,zinc content significantly decreased(P<0.05 or P<0.01),in the middle dose group,calcium,magnesium,zinc content significantly decreased(P<0.05 or P<0.01),in the high dose group,zinc,iron,calcium,manganese,copper content significantly increased(P<0.05 or P<0.01).(3)Compared with the control group,in hippocampus tissue,there were no significant apoptosis of neuronal cells in low dose group and high dose group.And in cortical tissue,there were moderate apoptosis of neuronal cells in low dose group and high dose group,and neuronal apoptosis was strong expressed in middle group.(4)Compared with the normal control group,the activity of HK,PFK,PK and G-6-Pase in three dose groups in the brain extremely decreased(P<0.01).(5)Compared with the normal control group,in hippocampus tissue,the expression of Insr,Irs1,PI3K,Akt2,mTOR mRNA in three dose groups significantly decreased,the expression of GLUT-1 mRNA in three dose groups and GLUT-3 mRNA in middle dose group and high dose group significantly increased(P<0.05 or P<0.01).In cortex tissue,in low dose group,the expression of Irs1,mTOR and GLUT-3 increased and PI3K decreased.In middle dose group,the expression of Irs1,Akt2 increased and Insr,PI3K decreased.In high dose group,the expression of Insr,PI3K and GLUT-3 increased and Akt2 decreased,the differences reached significant level(P<0.05 or P<0.01).(6)The Western blot results showed that compared with the normal control group,the expression of GLUT-1 in three dose groups in hippocampus increased.In middle and high dose group,the differences reached significant level(P<0.05).The expression of GLUT-3 also increased,the differences in high dose group reached extreme level(P<0.01).[Conclusions]Lead exposed lead to body weight increase slowly,two price of mineral elements imbalance,neuron apoptosis increase,also affect the information transmission of insulin signal pathway and the ability of GLUT glucose transporter,decrease glycolysis and pentose phosphate pathway activity,leading to abnormal on glucose metabolism of neurons,affect the normal function of brain.