糙皮侧耳碱提水溶性多糖对肿瘤的抑制作用及其机制

Inhibitory effect of water-soluble polysaccharide alkali-extracted from Pleurotus ostreatus and its mechanism

目的:研究糙皮侧耳(Pleurotus ostreatus)碱提水溶性多糖对肿瘤的抑制作用,并探讨其作用机制。方法:通过碱液提取、乙醇沉淀、联合脱蛋白和柱层析方法,分离得到粗皮侧耳碱提水溶性多糖WPOP-N1;BalB/C小鼠前肢腋皮下注射S-180肉瘤细胞建立肿瘤小鼠模型,将60只雌性小鼠随机分为正常对照组、模型对照组、环磷酰胺阳性对照组(30 mg·kg-1)、WPOP-N1低、中和高剂量组(100、200和400mg·kg-1),每组10只。除正常对照组外,在每只小鼠的前肢腋皮下注射S-180肉瘤细胞悬液,对照组小鼠给予生理盐水,模型对照组小鼠给予脂多糖10mg·L-1。采用ELISA法检测各组小鼠血清TNF-α水平,评价WPOP-N1对巨噬细胞吞噬作用,NO和TNF-α水平的影响。结果:WPOP-N1低、中和高剂量组小鼠瘤质量分别为(2.38±0.55)、(1.79±0.64)和(1.37±0.51)g,均低于正常对照组[(3.71±0.81)g](P<0.05);WPOP-N1低、中和高剂量组抑瘤率分别为35.8%、51.8%和63.1%;WPOP-N1中、高剂量组荷瘤小鼠血清TNF-α水平高于正常对照组(P<0.05或P<0.01);腹腔巨噬细胞的吞噬能力高于正常对照组(P<0.05或P<0.01);WPOP-N1低、中和高剂量组小鼠腹腔巨噬细胞分泌NO和TNF-α水平升高(P<0.05),并具有剂量效应。结论:WPOP-N1具有显著的体内肿瘤抑制作用,其作用机制可能是活化巨噬细胞分泌NO和TNF-α,并增强巨噬细胞的吞噬能力。

Objective To study the inhibitory effect of water-soluble polysaccharide alkali-extracted from Pleurotus ostreatus and to clarify its mechanism.Methods The water-soluble polysaccharide WPOP-N1 from Pleurotus ostreatus were obtained by alkaline extraction,ethanol precipitation,and joint deproteinized and column chromatography methods.Forelimbs of BalB/C mice were subcutaneously injected with S-180 sarcoma cells to establish mouse tumor models.60 BalB/C mice were randomly divided into normal control group,model control group,cyclophosphamide（positive control） group,WPOP-N1 low,medium,high doses groups（100,200 and 400 mg·kg-1）,and there were 10 mice in each group.Besides normal control group,the mice in the other groups were subcutaneously injected with S-180 sarcoma cells suspensions,and the mice in normal control group were given saline and the mice in model control group were given lipopolysaccharide.The levels of serum TNF-α secreted were detected by ELISA method.The effects of WPOP-N1 on macrophage phagocytic function and the levels of NO and TNF-α were estimated.Results The tumor weights of mice in WPOP-N1 low,medium and high doses groups were（2.38±0.55）,（1.79±0.64）,and（1.37±0.51） g,respectively,which were lower than that in normal control group（3.71 g±0.81 g）（P0.05）;the anti-tumor rates of WPOP-N1 low,medium and high doses groups were 35.8%,51.8%,and 63.1%;the serum TNF-α levels of mice in WPOP-N1 medium and high doses groups were higher than that in normal control group（P0.05 or P0.01）;the phagocytic activities of peritoneal macrophages of mice in WPOP-N1 medium and high doses groups were higher than that in normal control group（P0.05 or P0.01）;the NO and TNF-α levels secreted by murine peritoneal macrophages in WPOP-N1 low,medium and high doses groups were increased（P0.05） and had a dose-response.Conclusion WPOP-N1 has a significantly inhibitory effect on tumor in vivo and its mechanism may be related to activating macrophages to secrete NO and TNF-α,and enhancing the phagocytic activities of macrophages.