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背景与目的通过对醋酸铅诱导大鼠脑细胞凋亡及对fos、jun、P53基因和一氧化氮合酶表达的影响,进一步揭示铅的神经毒作用机制。材料与方法成年SD大鼠经腹腔注射醋酸铅染毒,分别用原位末端标记法观测细胞凋亡,用SP法测定脑组织中fos、jun、P53及nNOS和iNOS的蛋白表达情况。结果25mg/kg、50mg/kg、100mg/kg剂量染铅组大鼠海马、皮层组织凋亡细胞数量明显增加,并和染铅剂量有良好的剂量效应关系;大鼠脑组织海马、皮层fos、jun、P53、iNOS表达阳性细胞数显著增加,表达强度有升高趋势;各剂量染铅组海马组织中nNOS表达明显升高,而皮层组织nNOS表达无明显变化;相关分析表明,铅诱导的神经细胞凋亡与fos、jun、P53及iNOS的表达呈正相关。结论在铅诱导神经细胞凋亡的过程中,高表达的NOS使得NO生成过多进而引起DNA损伤,激活P53,同时使fos、jun表达增加也可激活P53,启动凋亡过程,诱导细胞发生凋亡。
BACKGROUND & OBJECTIVE: To further investigate the neurotoxic mechanism of lead by inducing apoptosis of rat brain cells induced by lead acetate and its effect on the expression of fos, jun, P53 and nitric oxide synthase. MATERIALS AND METHODS Adult SD rats were injected intraperitoneally with lead acetate. Apoptosis was observed by in situ end labeling. The protein expressions of fos, jun, P53, nNOS and iNOS were determined by SP method. Results The number of apoptotic cells in hippocampus and cortex of 25 mg / kg, 50 mg / kg and 100 mg / kg dose groups significantly increased, and had a good dose-response relationship with the lead dose. The fos, jun, P53, iNOS positive cells increased significantly, the expression intensity increased; the nNOS expression in hippocampus of each dose of lead significantly increased, while the expression of cortical nNOS no significant change; correlation analysis showed that lead-induced nerve Apoptosis was positively correlated with the expression of fos, jun, P53 and iNOS. Conclusion In the process of lead-induced neuronal apoptosis, high expression of NOS causes excessive production of NO, which in turn leads to DNA damage and activation of P53. At the same time, increased expression of fos and jun activates P53, initiates apoptosis and induces cell apoptosis Death.