目的：观察金钗石斛多糖（Dendrobium nobile polysaccharides，DNP）对脂多糖（lipopolysaccharide， LPS）诱导的大鼠学习记忆减退及神经炎症的改善作用。方法：DNP（40、80、160 mg·kg-1·d-1）预防性给药7 d，侧脑室注射20µg LPS制备大鼠学习记忆减退模型。制模后d 5开始，Morris水迷宫法检测大鼠的空间辨别学习记忆能力。行为学检测结束后，HE染色观察大鼠海马神经元的细胞形态改变，RT-PCR及Western Blot分别检测大鼠海马组织中肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）、白介素1β（interleukine-1β，IL-1β）、转化生长因子β1（transforming growth factor-β1，TGF-β1）的mRNA及蛋白表达。结果：与假手术组比较，模型组大鼠在定位航行实验中逃避潜伏期明显延长，在空间探索实验中其校正潜伏期明显缩短；大鼠海马神经元排列散乱，部分神经元丢失，出现核固缩，嗜伊红染色；大鼠海马组织中TNF-α、IL-1β、TGF-β1 mRNA及其蛋白的表达量明显增加。DNP（40、80、160 mg·kg-1·d-1）给药组能改善大鼠学习记忆能力，对抗LPS引起的大鼠海马CA1区神经元损伤，并降低大鼠海马组织中TNF-α、IL-1β、TGF-β1的mRNA及蛋白表达。结论：DNP可减轻LPS诱导的大鼠学习记忆减退及神经元损伤，抑制其海马的炎症反应。%Objective:To investigate the protective effects and potential mechanisms ofDendrobium nobile polysaccharides(DNP) fromDendrobium nobileLindl. on learning and memory deficits induced by lipopolysaccharide(LPS).Methods:Rats were orally treated with DNP(40,80,160 mg·kg-1) for 7 days,followed by bilateral intra-cerebroventricular injection of LPS(20μg·rat-1) to induce learning and memory deficits. Rats were continued to receive DNP until the end of experiments. Morris water maze was used to test the abilities of spatial learning and memory. The neuronal injury in hippocampus was observed by hematoxylin-eosin staining. The mRNA and protein expressions of neuroinflammation-related genes and proteins in rats hippocampus were detected by real time RT-PCR and Western blot,respectively.Results:Compared to sham(saline-injected) rats,LPS significantly prolonged the escape latency in the navigation test and shortened the adjusted escape latency(P<0.01). These learning and memory deficits were significantly improved by DNP treatment(P<0.01). LPS injection caused neuronal injury in hippocampus,and increased the mRNA and protein expressions of TNF-α,IL-1β and TGF-β1 in rat hippocampus(P<0.01),which were suppressed by DNP treatments(P<0.05). Conclusions:DNP could protect LPS-induced learning and memory deficits and neuronal injury in rats. The mechanisms appear to be due to the inhibition of LPS-elicited inflammatory responses in the hippocampus.
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