慢性铝暴露对大鼠海马神经元PKC、CaMKⅡ、Ng 的影响

通过研究慢性铝暴露对大鼠学习记忆和海马长时程增强 (long-term potentiation, LTP) 的影响，并检测海马神经元蛋白激酶Ｃ(protein kinase c, PKC) 活性及Ca²⁺钙调蛋白激酶Ⅱ(Ca²⁺calmodulin dependent protein kinase Ⅱ, CaMK Ⅱ) 和神经颗粒素(neurogranin, Ng) 蛋白表达的变化，探讨铝暴露损害学习记忆的作用机制.选用断乳后 Wistar 大鼠，以含有不同浓度 AlCl₃ 的蒸馏水进行饲养.3 个月后，测定铝暴露组大鼠脑内和血中的铝含量；测量记录大鼠海马群体峰电位(population spike,PS)LTP；用改良 Takai 法测定海马神经元 PKC 活性变化；Western 印迹法检测 CaMK Ⅱ和Ng的蛋白表达.结果显示，与对照组相比,铝暴露组的 PKC 活性降低，差异有统计学意义 (P<0.01)；与对照组相比,铝暴露组的CaM Ⅱ蛋白表达降低，差异有统计学意义(P<0.05)；与对照组相比,铝暴露组的 Ng 蛋白表达降低，且差异有统计学意义(P<0.05).实验结果说明：慢性铝暴露可以降低大鼠海马神经元 PKC 的活性及 Ng 和 CaMKⅡ 的蛋白表达，可能影响 Ng 磷酸化水平，从而影响 CaM 与 Ng 之间的亲和性，也影响 Ca²⁺CaM 对 CaMKⅡ 的调节，抑制 LTP 的形成，损害学习记忆的功能.

Effect of Chronic Aluminum Exposure on PKC,CaMK Ⅱ and Neurogranin in Hippocampus of Rat

To investigate the mechanism of aluminum induced impairments to learning and memory, the effects of chronic aluminum exposure on long term potentiation (LTP) were studied. The activity of protein kinase C (PKC) was determined and the Effect of aluminum on protein expressions of Ca²⁺/calmodulin dependent protein kinase Ⅱ (CaMKⅡ) and neurogranin (Ng) were detected. The ablactated Wistar rats were used to establish the chronic aluminium exposure models by the gavage of AlCl-3 of different concentrations in the drinking water. And 3 months later, the concentrations of aluminum in brain and blood were measured, PS(population spilke) LTP in hippocampus of the rat was recorded, and then the activity of PKC was determined by modified Takai Method. Western blotting was used to determine the protein expressions of CaMKⅡ and Ng in hippocampus. The PKC activity of AlCl-3 exposure groups is obviously lower than that of control groups (P<0.01). The protein expression of Ng in the hippocampi of AlCl-3 exposure groups falls down comparing with that of control groups in a dose dependent manner (P<0.05).The protein expression of CaMKⅡ in the hippocampi of AlCl-3 exposure groups is lower than that of control groups in a dose dependent manner too (P<0.05). Chronic aluminum exposure can reduce not only the activity of PKC but also the protein expressions of CaMKⅡ and Ng and the phosphorylation level of Ng, thus affecting the affinity between Ng and calmodulin (CaM). The adjustment and modulation of Ca²⁺CaM complex to CaMKⅡ were also impacted, inhibiting the formation of LTP and damaging learning and memory.