中文摘要：

为了探讨凋亡和ERK信号与镉诱导大鼠大脑皮质神经细胞自噬的关系，本研究用20μmol／L镉作用大鼠大脑皮质神经细胞4h，免疫荧光观察自噬小体，吖啶橙染色观察酸性自噬泡的形成；20μmol／L镉单独或联合氟喹作用4h、联合雷帕霉素或caspase抑制剂玉VAD-fmk作用24h，DAPI荧光染色观察细胞核的变化；20μmol／L镉联合ERK抑制荆U0126作用4h，免疫印迹检测ERK、LC3的表达变化。结果表明：镉处理4h，大脑皮质神经细胞发生明显的聚点现象，吖啶橙染色可见酸性自噬泡的形成；与正常组比较，镉处理24h后神经细胞出现染色质固缩、核碎裂；镉联合氯喹作用4h，损伤的神经细胞增多，出现新月状、浓缩的胞核，甚至出现核碎裂；而镉联合雷帕霉素或Z—VAD-fmk组，细胞的损伤明显减轻。U0126能明显抑制原代神经细胞ERK1／2的磷酸化水平，同时还能显著抑制LC3-II的表达（P〈0．05）。说明镉诱导的自噬可以延迟凋亡的发生；ERK是自噬的上游信号分子，它的激活有利于诱导自噬。

英文摘要：

To elucidate the relationship between apoptosis,ERK signal and the autophagy, the neurons were treated with 20mol/L cadmium for 4 h,autophagosoraes were observed hy immunofluorescence and AVOs were surveyed by AO staining. Neurons were pretreated with CQ for 0.5 h, followed by treatment with cadmium for another 4 h,or pretreated with RAPand Z-VAD-fmk for 24 h, followed by treatment with cadmium for another 24 h, morphological changes were detected DAPI staining, neuron cells were treated with 20μmol/L Cd for 4 h following pre-incubation with U0126, a ERK inhibitor for 0.5 h, ERK and LC3 were examined by immunoblotting. Data indicated that LC3 puncta was observed apparently after neurons were treated for 4 h with 20μmol/L cadmium. AO staining discovered the existence of AVOs. In comparison with the control neurons group,the cells in cadmium-treated for 24 h and co-treatment CQ and cadmium for 4 h showed typical morphological changes of apoptosis with nucleus crimpled and chromatin condensedation, even nucleus disintegratation. However, co-treatment with cadmium and RAP or Z-VAD-fmk,cell injuries were alleviated. U0126 significantly decreased the levels of P-ERK1/2, LC3-II, which suggested that autophagy hinders apoptosis in Cd-treated neurons, ERK is a upstream signaling molecule of autophagy,the activation of which is in favor of autophagy.