Effects of aluminum on the intracellular calcium concentration and the expression of calcium channels in the hippocampus of rats / 中国地方病学杂志

ABSTRACT

Objective To dynamically investigate the effects of aluminum on the concentration of free intracellular Ca2+([Ca2+]i) and the expression of calcium channels in the hippocampus of rats. Methods Healthy 64 Wistar rats were taken as the experimental objects. And these rats were randomly divided into 16 groups according to their weights, and were instilled with AlCl3 at 0(control),37.3,74.7 and 248.7 mg/kg respectively. The experimental time exposed to AlCl3 was 45,75,120 d, among which the rats were given AlCl3 for 120 d fed normally for 30 d. The hippoeampus were segregated on day 45,75,120 and 150 d and the[Ca2+]i of hippocampus of rats were detected by fluorospectrophotometer. The expression of Ryanodine receptor 2 (RyR2) mRNA and α1C ubunit of L-type calcium ehannels(L-Ca2+α1C) mRNA were detected by RT-PCR analysis. Results [Ca2+]i was increased by AlCl3 in a dose-and time-dependant manner(F=23.136 and 19.089, P<0.01). There was a synergistic effect between the dose and time in [Ca2+]i (F=2.270, P<0.05). In time of 120,150 days, the [Ca2+]i of rats hippocampus in 37.3[(299.3±48.7), (342.7±35.3)nmol/L], 74.7[(391.2±47.9), (408.1±42.8)nmol/L] and 248.7 mg/kg group[(397.9±55.8), (405.2±22.7)nmol/L] significantly increased compared with control group [(195.1±29.9), (209.1±30.6)nmol/L; P<0.01]. The expression of RyR2 mRNA and L-Ca2+α1C mRNA were increased by AlCl3(F=23.301 and 60.812, P<0.01). The experimental time could lower the expression of L-Ca2+ α1C mRNA (F=6.088, P<0.01), but had no influences on the expression of RyR2 mR NA (F=1.361, P>0.05). There was interaction between the dose of AlCl3 and the time in the expression of L-Ca2+α1C mRNA (F=5.876,P< 0.01). On day 75,120 and 150 of the experiment, the expression of L-Ca2+α1C mRNA in rat hippocampus of 74.7 (1.03±0.16,1.18±0.18,0.92±0.11) and 248.7 mg/kg group(1.89±0.26, 1.25±0.10, 1.07±0.14) also increased compared with control group(0.63±0.09,0.78±0.16,0.69±0.11; P<0.05 or <0.01). On day 45,75, 120 and 150 of the experiment, the expression of RyR2 mRNA in 74.7(0.49±0.06,0.51±0.07,0.57±0.11, 0.47±0.11), 248.7(0.47±0.03,0.52±0.09, 0.70±0.10, 0.78±0.09)mg/kg AlCl3 groups was highly increased compared with control group (0.24±0.07, 0.32±0.04, 0.30±0.06, 0.27±0.06; P<0.05 or<0.01). Conclusion Al increases [Ca2+]i by increasing the expression of the RyR2 mRNA and L-Ca2+α1C mRNA, thus exerts an irreversible neuronal toxicity.