| Lead poisoning is one of the geochemical diseases, which has been shown to be toxic tothe liver and kidney, and is highly carcinogenic. Lead could pass the blood-brain barrier,reduce the learning and memory ability and damage the structural of cerebral cortex andhippocampus. However, little is known about the mechanism of lead poisoning. In order tostudy further mechanism of lead poisoning, the Kunming mice were used to explore theeffects of different concentrations of lead acetate (0,2.4,4.8,9.6mmol/L) on cerebral cellmorphology and the expression of microtubule-associated protein2(MAP2) in this study.The Kunming mice were orally administered with lead acetate to detect its median lethaldose (LD50) by Bliss method, and some indexes, which included body weight, organ relativeindex, lead level in blood, necropsy and histopathology, were analyzed to certify the animalmodel of lead poisoning. The changes of morphology and ultrastructure of nerve cell in miceexposed to lead were observed by standard optical microscopes and electron microscope. Thedistribution of lead in the nerve cell in mice were analyzed by Energy Dispersive Spectrometer(EDS).The change of MAP2mRNA expression was detected by Real-time quantitative polymerasechain reaction (q-PCR), and the changes of MAP2protein expression were detected byWestern Blot.The results of lead acute toxicity experiment showed that the LD50of lead acetate inmice is10562mg/kg, and it was low toxic substance. The body weight gain of mice was notrelevant significantly with the dosage rising of lead acetate. Compared with the control group,the kidney relative index in low dosage group (2.4mmol/L) was increased significantly(P<0.05), and it was increased highly (P<0.01) in the4.8and9.6mmol/L groups, and therelative indexes of the rest organs were no significant difference (P>0.05). The tissues of mice,such as cardiac, spleen and kidney, swelled out, especially in high dosage group (9.6mmol/L).Cardiac fibers were broken, the alveolar wall were gathered, the liver cords arrangeddisorderly and there were different sizes of liver cells. Spleen hemorrhage was obviouse, thecavity of renal tubule were shrinked and the mount of maculae densa were increased.The results of morphological test with standard optical microscopes showed the number andmorphologic structure of granule cells and pyramidal cells in mice brain were no remarkable changein2.4mmol/L group, compared with the controls. The number of granule cells wre decreasedand molecular layer were breaked in4.8mmol/L and9.6mmol/L groups, especially in 9.6mmol/L groups. The results of TEM experiments showed that the nuclear membrane andmitochondrial cristae in nerve cells were seen clear in the controls. The neurons in cortex ofmice exposed to lead were observed obvious changes: mitochondria swelled, chromatinaggregated, perinuclear space enlarged, nuclear membrane damaged and cristae mitochondriafractured and lost, microtubule shortened and tangled and the number of it was decreased.The results of the energy spectrum analysis showed that lead could pass the blood-brainbarrier and has been found in nucleopore, chromatin and nuclear membrane in nerve cell inexperimental groups. The content of lead in brain cell was increased with exposed dosageraise of lead acetate.Real-time quantitative polymerase chain reaction analysis showed that the expression ofMAP2mRNA of nerve cells in experimental groups were decreased remarkably comparedwith the cotrols(P<0.05), and the expression of2.4mmol/L,4.8mmol/L and9.6mmol/Ldosage groups are0.336,0.347and0.553times of0mmol/L dosage group respectively.The result of Western blot showed that the protein expression of MAP2was decreased inexperimental groups compared with the controls. The value of the controls,2.4,4.8and9.6mmol/L groups were12666.9,8638.0,4471.3and2553.1respectively.The study suggested that high dosage lead could cause a significant dose-dependent toxic effect oncerebral cells morphology and the microtubule-associated protein2(MAP2) in mice. |
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