亚慢性铝染毒对大鼠海马长时程增强及小G蛋白RAS和细胞外调节蛋白激酶的影响

Effects of subchronic aluminum exposure on long-term potentiation and activities of RAS and extracellular regulated protein kinases in rats

目的研究在亚慢性铝染毒致大鼠海马长时程增强（Long-term potentiation，LTP）损害的过程中，小G蛋白RAS及其下游的细胞外调节蛋白激酶（extracellular regulated protein kinases，ERK）活力的变化。方法健康成年雄性Wistar大鼠24只，随机分为对照组、低剂量组、中剂量组和高剂量组，每组6只。采用腹腔注射麦芽酚铝[Al（mal）3]的方式对大鼠进行染毒，对照组给予生理盐水，低、中、高剂量组的染毒剂量分别为15、30和45 μmol/kg，连续染毒5 d后休息2 d，持续8周。染毒结束后采用在体海马CA1区LTP记录技术，记录兴奋性突触后电位（fEPSP）；然后断头取海马，并提取总蛋白，采用酶联免疫吸附测定法（ELISA）分别测定RAS和ERK活力。结果LTP检测结果显示，对照组在高频刺激（HFS）后1、30和60 min fEPSP幅度分别为1.90±0.19，1.64±0.15和1.54±0.08；低剂量组在60 min时fEPSP幅值是1.40±0.06，与对照组比较，差异有统计学意义（P〈0.05）；中剂量组在30 min和60 min时fEPSP幅值分别下降到1.33±0.20和1.12±0.07，与对照组比较，差异有统计学意义（P〈0.05）；高剂量组在30 min和60 min fEPSP幅值进一步下降到1.05±0.05和0.91±0.10，分别与对照组、低剂量组和中剂量组比较，差异有统计学意义（P〈0.05），在高频刺激后，随着染铝剂量的增加fEPSP幅值出现剂量依赖性的降低。ELISA检测结果显示，对照组、低、中、高剂量组大鼠的RAS活力分别为12 245±765、11 567±531、8 560±476和6 578±608，ERK的活力分别为0.35±0.02、0.31±0.03、0.23±0.02和0.16±0.02，与对照组和低剂量组比较，中剂量组与高剂量组RAS和ERK活力降低，差异有统计学意义（P〈0.05）；与中剂量组比较，高剂量组RAS和ERK活力降低，差异有统计学意义（P〈0.05）。结论RAS及ERK与铝抑制大鼠海马LTP的机制有关，RAS-MAPK通路可能是铝致学习记忆损害的作用机制之一。

ObjectiveTo study the effects of subchronic aluminum exposure on LTP and activities of RAS and ERK in rats in vivo.Methods24 Wistar rats were randomly divided into control group、low-dose group、medium-dose group and high-dose group, and received saline （control group） or Al （mal） 3 （15 μmol、kg、30 μmol、kg or 45 μmol/kg） via intraperitoneal injection （i.p.） for 8 weeks, respectively. The fEPSP in CA1 region were recorded by field potentiation technique in vivo and the hippocampal activities of RAS and ERK were examined by ELISA.Results The fEPSP amplitudes of the control group were 1.90±0.19, 1.64±0.15 and 1.54±0.08 at 1, 30 and 60 min after HFS, respectively. The fEPSP amplitudes of the low-dose group were 1.40±0.06 at 60 min, which represented a statistically significant decrease compared to the control group （P〈0.05） ; these values at 30min and 60min dropped to 1.33±0.20 and 1.12±0.07 in the medium-dose group （P〈0.05） and further decreased to 1.05±0.05 and 0.91±0.10 in the high-dose group （P〈0.05） . And the activity dose-dependent decreases were observed both in RAS and ERK： compared with the control group and the low-dose group, the activities of RAS and ERK of the medium-dose and high-dose group significantly decreased （P〈0.05） and compared with the medium-dose group, the activities of the high-dose group statistically dropped （P〈0.05） .ConclusionRAS and ERK may be related to the suppression of LTP by subchronic aluminum exposure and the RAS-MAPK transduction pathway may be involved in the damage of learning and memory induced by aluminum.