关键词: 铅;神经毒性;凋亡;fos基因;jun基因, p53基因;一氧化氮合酶

Abstract: BACKGROUND ＆ AIM: To study the effect of lead acetate on the apoptosis and the expression of fos, jun, P53 and NOS and to provide some scientific basis for further delineation of the neurotoxic mechanisms of lead. MATERIAL AND METHODS: Mature and healthy Sprague-Dawley rats were randomly divided into four groups. Lead acetate was injected intraperitoneally. The determination of apoptosis in hippocampus and cerebral cortex was made by terminal-deoxynucleotidyl transferase mediated d-UTP nick and labeling(TUNEL). The expression of fos, jun, P53 genes and nNOS, iNOS in hippocampus and cerebral cortex were measured by using immunohistochemical method. RESULTS: ① TUNEL showed that lead acetate induced apoptosis of cells from hippocampus, cerebral cortex in every treatment group (P<0.05), and there was a significant dose-response relationship.② The expression of fos, jun, P53 and iNOS increased in neural cells from hippocampus, cerebral cortex in every lead acetate treatment group compared with the control.③ The expression of nNOS significantly increased in hippocampus in every treatment group compared with the control.However the expression of nNOS in cerebral cortex showed no significant difference between the treatment groups and the control group.④ Correlation analysis demonstrated that apoptosis correlated positively with the expression of fos, jun, P53 and iNOS. CONCLUSION: The overexpression of P53, which was caused by damage of DNA elicited by the excessive amount of NO from the overexpression of NOS, induced apoptosis of neural cells. Lead acetate also induced the prolonged expression of fos and jun which may initiate the expression of P53 followed by apoptosis of neural cells.

Key words: lead, neurotoxicity, apoptosis, fos gene, jun gene, nitric oxide synthase