Phenylethanoid glycosides of Pedicularis muscicola ameliorate high altitude-induced memory impairment by activating mTOR signal pathway
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摘要: 目的 探讨藓生马先蒿苯乙醇苷（phenylethanoid glycosides，PhGs）改善高原记忆损伤的机制，明确其是否通过激活mTOR信号通路来实现的。 方法 清洁级雄性Wistar 大鼠60只，随机分为常氧对照组、缺氧组、PhGs低、中、高剂量组（50、200、400 mg/kg灌胃给药），常氧对照组和缺氧组给予等体积的灭菌注射用水，连续给药7 d。给药第4天，缺氧组和PhGs低、中、高剂量组置于大型低压氧舱模拟高原低压低氧环境（7 500 m，3 d）。采用SYBR Green 实时定量聚合酶链式反应（PCR）检测海马组织中mTOR、P70S6K和4E-BP1 mRNA表达；蛋白质印迹法（Western blot）检测海马组织中p-mTOR、p-P70S6K和p-4E-BP1 蛋白表达。 结果 与常氧对照组比较，缺氧组海马组织中mTOR、P70S6K mRNA表达分别下调达22.50%、26.00%（P<0.05，P<0.01），4E-BP1 mRNA表达上调达41.28%（P<0.01）；p-mTOR和p-P70S6K蛋白表达分别降低42.28%和11.70%（P<0.05，P<0.01），p-4E-BP1蛋白表达升高111.86%（P<0.01）。与缺氧组比较，PhGs低剂量组4E-BP1 mRNA表达下调达77.33%（P<0.01），p-P70S6K蛋白表达升高32.53%（P<0.01），p-4E-BP1蛋白表达降低82.4%（P<0.01）；PhGs中、高剂量组海马组织中mTOR、P70S6K mRNA表达分别上调达64.56% 、60.76% 和14.86%、20.27%（P<0.01），4E-BP1 mRNA 表达分别下调达72.67%、71.57%（P<0.01），p-mTOR、p-P70S6K蛋白表达分别升高65.12%、94.17%和56.63%、78.31%（P<0.01），p-4E-BP1蛋白表达分别降低57.6%和40%（P<0.01）。 结论 藓生马先蒿苯乙醇苷能够改善高原记忆损伤，其保护机制可能是通过激活mTOR信号通路实现的。Abstract: Objective To investigate the mechanism of phenylethanoid glycosides of pedicularis muscicola Maxim ameliorating high altitude memory impairmentby activating mTOR signal pathway. Methods 60 clean male Wistar rats were randomly divided into normoxic control group, hypoxia group, PhGs low, medium and high dose groups(50, 200, 400 mg/kg by oral administration). Normoxic control and hypoxia groups were administered with sterile injection water for 7 days. On the fourth day of drug treatment, hypoxia and PhGs groups were exposed to a specially designed animal decompression chamber, which simulated 7 500 m high altitude environment. The expression levels of mTOR, P70S6K and 4E-BP1 mRNA in hippocampus were detected by SYBR Green real-time PCR. The expression levels of p-mTOR, p-P70S6k and p-4E-BP1 protein in hippocampus were detected by Western blot. Results For hypoxia group rats, mTORand P70S6k mRNA repression, p-mTOR and p-P70S6K protein repression were respectively decreased by 22.50%, 26.00%, 42.28% and 11.70%(P<0.05, P<0.01), 4E-BP1 mRNA repression and p-4E-BP1 protein repression were respectively increased by 41.28%, 111.86%(P<0.01) in comparison tonormoxic control group.Compared with hypoxia group,for PhGs low dose group rats, 4E-BP1 mRNA repression and p-4E-BP1 protein repression were respectively decreased by 77.33% and 82.4%(P<0.01), p-P70S6K protein repression was increased by 32.53%(P<0.01). For PhGs medium, high dose groups, mTOR and P70S6k mRNA repression,p-mTOR and p-P70S6K protein repression were respectively increased by 64.56%, 60.76%; 14.86%, 20.27%; 65.12%, 94.17% and 56.63%, 78.31%(P<0.01), 4E-BP1 mRNA repression and p-4E-BP1 protein repression were respectively decreased by 72.67%, 71.57% and 57.6%, 40%(P<0.01). Conclusion Phenylethanoid glycosides of Pedicularis muscicola Maxim can ameliorate high altitude-induced memory impairment. This protective mechanism may due to the activation of mTOR signal pathway.
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