Zinc ion (Zn²⁺) is an important functional factor; however, excessive Zn²⁺ can be toxic. To understand the neurotoxicity of excessive Zn²⁺ and the underlying mechanism, PC12 cells were treated with excessive Zn²⁺ and Zn²⁺ plus N, N, N′, N′-Tetrakisethylenediamine (TPEN), a zinc ion chelator agent. Trypan blue and 3-(4,5-dimethyl-2- thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays were used to test cell viability; the relative kits were used to detect the activity of NOS synthase and the content of the receptor for advanced glycation end product (RAGE) in cells. We observed that excessive zinc caused PC12 cell damage and that TPEN partially reversed cell damage caused by excessive zinc. In addition, excessive zinc decreased total nitric oxide synthase (TNOS) activity in cells, in which constitutive nitric oxide synthase (cNOS) activity was significantly reduced; however, inducible nitric oxide synthase (iNOS) activity was extremely promoted. Moreover, excessive zinc upregulated the expression of RAGE, and TPEN effectively reversed the increase in RAGE induced by excessive zinc ions. Therefore, we concluded that excessive zinc caused PC12 cell damage, correlating with the inhibition of NOS and increase of RAGE induced in cells.

锌离子（Zn ²⁺）是重要的功能因子；然而，过量的Zn ²⁺可能是有毒的。为了了解过量 Zn ²⁺的神经毒性及其潜在机制，用过量 Zn ²⁺和 Zn ^{2+处理 PC12 细胞}加上 N, N, N', N'-四乙二胺 (TPEN)，一种锌离子螯合剂。台盼蓝和 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-溴化四唑、噻唑蓝溴化四唑 (MTT) 测定用于测试细胞活力；相关试剂盒用于检测细胞内NOS合酶活性和晚期糖基化终产物受体(RAGE)的含量。我们观察到过量的锌导致 PC12 细胞损伤，而 TPEN 部分逆转了过量锌引起的细胞损伤。此外，过量的锌降低了细胞中总一氧化氮合酶（TNOS）的活性，其中组成型一氧化氮合酶（cNOS）活性显着降低；然而，诱导型一氧化氮合酶（iNOS）的活性得到了极大的促进。此外，过量的锌上调了 RAGE 的表达，TPEN 有效地逆转了过量锌离子引起的 RAGE 增加。因此，我们得出结论，过量的锌会导致 PC12 细胞损伤，这与细胞中 NOS 的抑制和 RAGE 的增加有关。