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铁皮石斛生物碱对脂多糖诱导大鼠记忆障碍的抑制作用。

Inhibitory effects of Dendrobium alkaloids on memory impairment induced by lipopolysaccharide in rats.

机构信息

Department of Pharmacology, Zunyi Medical College, Zunyi, PR China.

出版信息

Planta Med. 2011 Jan;77(2):117-21. doi: 10.1055/s-0030-1250235. Epub 2010 Aug 17.

Abstract

Dendrobium alkaloids (DNLA), extracted from Dendrobium nobile Lindl. whose botanical name is Dendrobium moniliforme, Orchidaceae family, were studied for their effect on lipopolysaccharide (LPS)-induced memory impairment in rats. SD rats were pretreated with DNLA (40, 80, 160 mg/kg/d for 7 d), followed by LPS (50 µg) injection into the right lateral ventricle to produce memory impairment. DNLA treatment continued for another 13 days. The spatial behavior was tested by the Morris water maze; the level of tumor necrosis factor receptor 1 (TNFR1) mRNA was detected by real time RT-PCR, and the protein level of TNFR1, nuclear factor kappa-B (NF- κB) and phosphorylated p38 mitogen-activated protein kinases (p-p38 MAPK) by Western blotting. The results showed that DNLA significantly improved the neurobehavioral performance and prevented LPS-induced elevation in TNFR1 mRNA and protein levels. LPS-induced activation of p38 MAPK and NF- κB pathway was also suppressed. In conclusion, DNLA is effective in protecting against LPS-induced brain impairment, and this effect is due, at least in part, to prevent overexpression of TNFR1 via inhibition of p-p38 MAPK and the downstream NF- κB signal pathway.

摘要

铁皮石斛生物碱(DNLA)从兰科植物铁皮石斛(Dendrobium moniliforme)中提取,研究其对脂多糖(LPS)诱导的大鼠记忆障碍的影响。SD 大鼠用 DNLA(40、80、160mg/kg/d,预处理 7d)预处理,然后将 LPS(50μg)注射到右侧侧脑室以产生记忆障碍。DNLA 治疗继续进行 13 天。通过 Morris 水迷宫测试空间行为;实时 RT-PCR 检测肿瘤坏死因子受体 1(TNFR1)mRNA 水平,Western blot 检测 TNFR1、核因子 κB(NF- κB)和磷酸化 p38 丝裂原激活蛋白激酶(p-p38 MAPK)蛋白水平。结果表明,DNLA 显著改善了神经行为表现,防止了 LPS 诱导的 TNFR1 mRNA 和蛋白水平升高。LPS 诱导的 p38 MAPK 和 NF- κB 通路的激活也受到抑制。总之,DNLA 有效防治 LPS 诱导的脑损伤,这种作用至少部分是通过抑制 p-p38 MAPK 和下游 NF- κB 信号通路来防止 TNFR1 的过度表达。

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