Objective: To study the effects of subchronic aluminum exposure on LTP and activities of RAS and ERK in rats in vivo. Methods: 24 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) . Conclusion: RAS 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.
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。.
Keywords: Aluminum; Long-term potentiation; Protein kinases; Ras proteins.