【摘要】 目的制何首乌(Polygoni Multiflori Radix Praeparata, PM)是常用的补益肝肾中药,近年来由何首乌及其制剂引起的肝损伤受到广泛关注。本研究旨在探索制何首乌造成免疫特异质肝损伤的化学物质和配伍减毒机制。方法本研究以脂多糖(Lipopolisaccharide,LPS)诱导免疫特异质体质,利用中药组分敲除技术,筛选制何首乌特异质肝脏损伤的化学物质;选择多种具有免疫调节作用的中药多/寡糖,探究其与制何首乌配伍后的减毒作用。结果在LPS诱导的免疫应激动物模型中,PM醇提物造成免疫特异质肝损伤。PM提取物中敲除蒽醌类成分后,其肝损伤作用明显降低;而PM中分离的蒽醌类成分能引起动物免疫特异质肝损伤。肉苁蓉多糖、褐藻寡糖、壳寡糖与制何首乌配伍,均能减轻制何首乌造成的免疫特异质肝损伤,抑制多种炎症因子表达。结论免疫特异质体质是导致制何首乌肝毒性的重要因素,蒽醌类成分是造成其肝损伤的主要物质基础,肉苁蓉多糖、褐藻寡糖、壳寡糖能减轻PM造成的特异质肝损伤。更多还原

【Abstract】 Objective Polygoni Multiflori Radix(PM, He-Shou-Wu), is used as a reputable tonifying traditional Chinese medicine for a long time. However, in recent years, the liver injury caused by PM or its preparations attracted wide attention. This research was to investigate the mechanism, material basis and attenuation of PM induced idiosyncratic liver injury. Methods In this study, we investigated the molecular basis of PM-induced liver injury based on a non-hepatotoxic dose of LPS. A component “knock-out” strategy with TSG(2,3,5,4’-tetrahydroxy stilbene-2-O-β-D-glucopyranoside) or AN(anthraquinone) eliminated was used to study the material basis for PM-induced liver injury. Finally, some polysaccharides and oligosaccharides were selected to explore their toxicity attenuated effects when used compatible with PM. Results In LPS-induced immune stress mice or rats, PM caused immune-idiosyncratic liver injury. After knockout anthraquinones(AN) from PM(PM-AN), the liver injury was significantly reduced and the AN isolated from PM also caused immune-idiosyncratic liver injury.Pretreatment with Cistanchedeserticola polysaccharide(CDP), Alginate oligosaccharide(AO), Chitosan oligosaccharide(CO) could attenuate the PM-induced liver injury and inhibit the expression of various cytokines. Conclusion The immune-idiosyncratic constitution is an important factor leading to the liver injury of PM. Anthraquinone is a major material basis of PM-induced liver injury. Polysaccharides or oligosaccharides could attenuate PMinduced liver injury, which was related with immune-modulatory effects.更多还原