摘要
目的探讨心，娟对哺乳动物雷帕霉素靶蛋白mTOR／核糖体亚基S6蛋白激酶（p70S6K）信号转导通路及凋亡相关基因表达的影响，观察人参皂甙Rg1对Aβ25-35；引起细胞凋亡的对抗作用和作用机制。方法取SD大鼠30只，随机分为5组，每组6只，即生理盐水对照组、鹪，埘损伤组、A＆5嘣＋Rg1（20、40、80mg／kg）3个剂量组。连续用Rg1灌胃3周后，脑室注射觞，娟10μL（1．0mmol／L），生理盐水对照组注射等量生理盐水。脑室注射后7d，快速取海马CA1区，-70℃冰箱冻存，ImPCR分析mTOR、p70S6K以及凋亡相关基因c—fos、Jun-B、c-jun的mRNA表达水平。结果脑室内注射Aβ25～35能使mTOR和p70S6K的mRNA表达水平降低，使凋亡相关基因c—fOS、Jun-B、c-jHn的mRNA表达明显增加。Rg1可剂量依赖性对抗鹅5哂引起的p70S6KmRNA表达水平降低及c—los、Jun—B、c—jun的mRNA表达水平增加。结论mTOR／p70S6K信号转导通路下调可能参与了Aβ25～35引起的海马神经细胞的凋亡，Rg1通过对抗心5～35引起mTOR／p70S6K信号转导通路下调，抑制促凋亡基因的表达，保护海马神经细胞。
Objective To explore the effects of Aβ25～35 on mTOR/p70S6K signal transduction pathway and the apoptosis- related gene expressions. Methods Thirty Sprague - Dawley rats were randomly divided into five groups with six ones in each group： the control group using physiological saline, the group of Aβ25～35 and the groups of Aβ25～35＋ Rgl of 20,40 and 80 mg/kg. The rats were administrated with intracerebroventricular injec- tion after using the lavage of Rgl for 3 weeks. Equivalent dose of physiological saline was used in the contrast group, hippocampal CA1 region was removed seven days later and received cryopreservation and the analysis of the levels reverse transcription- polyrnerase chain reaction （RT- PCR）of mTOR/p70S6K and the apoptosisrelated gene expressions of c - los, and Jun - B mRNA. Results Intracerebroventricular injection of Aβ25～35 signif- icantly downregulated the expressions of mTOR and p70S6K mRNA levels in hippocampal CA1 regions. These changes were accompanied by the elevated levels of c - fos,Jun- B and c -jun rnRNA. Pretreatment of Rgl 20, 40,80 mg/kg. Conclusion The downregulation of mTOR/p70S6K levels may contribute to the apoptosis evoked by Aβ25～35. Rgl can protect hippocampal neurons through inhibiting the expressions of apoptotic genes by upregulation of mTOR/p70S6K in rat hippocampus.
