铝对大鼠海马[Ca^(2+)]i和PKC生物活性影响

Effect of chronic aluminum exposure on [Ca^(2+)]i and bioactivity of PKC in hippocampus of rat

目的通过观察不同浓度慢性铝暴露对海马长时程增强(long-termpotentiation,LTP)的影响,检测海马细胞内Ca2+浓度和蛋白激酶C(PKC)生物活性,研究慢性铝暴露损伤学习记忆的机制。方法选择断乳后Wistar大鼠,以含有不同浓度AlCl3的蒸馏水进行饲养。3个月后,测定脑铝、血铝、海马细胞内Ca2+,测量记录大鼠海马LTP,用改良的Takai法测定PKC活性的变化。结果(1)各染铝组的[Ca2+]i与对照组比较,差异有统计学意义(P<0.01),但各染铝组间差异无统计学意义。(2)各染铝组PKC活性与对照组比较均降低,差异有统计学意义(P<0.01)。结论慢性铝暴露引起大鼠海马细胞内[Ca2+]i下降,使PKC活性降低,导致下游分子的活性受到影响,破坏LTP的形成,损害学习记忆功能。

Objective To go deep into the mechanism of chronically aluminum-induced impairments to memory through observing the effects of chronic aluminum exposure on long-term potentiation（LTP） and studying the changes of Ca^2＋ concentration in hippocampus and protein kinase C. Methods The ablactated Wistar rats were used to establish the chronic-aluminium exposed models by the gavage of AlCl3 of different concentrations in the drinking water to determine the levels of Al in brain, blood and intracellttlar calcium individually, and to measure the LTP in hippocampi of the rats three months later, and then determine the activity of protein kinase C（PKC） with modified Takai method. Results （1）The calcium concentration of AlCl3 exposed groups was lower than that of control groups（ P 〈 0.01 ）, but there was no distinctive difference between the AlCl3 exposed groups. （2）The PKC activity of AlCl3 exposed groups was obviously lower than that of control groups （P 〈 0.01 ）. Conclusion Chronic aluminium exposure can decline the concentration of calcium in hippocampus and reduce the activity of PKC, thus affect the activity of its downstream kinases, damaging the formation of LTP and consequently impairing the ability of learning and memory.