纹党参多糖联合环磷酰胺对S_(180)荷瘤小鼠抗肿瘤增效机制的研究

Study on Synergetic Mechanism of Polysaccharide Extracted from WenXian DangShen Combined with Cyclophosphamide in Fighting against S_(180) Tumor of the Mice

目的:研究纹党参多糖对环磷酰胺抗肿瘤作用的增效效应及作用机制。方法:选用健康成年昆明种小鼠135只,随机分为9组:正常对照组(ZD组),荷瘤对照组(HD组),环磷酰胺组(CP组),纹党参多糖高(WCPP-G组)、中(WCPP-Z组)、低(WCPP-D组)剂量治疗组及WCPP-G、WCPP-Z、WCPP-D联合CP组,每组15只。除ZD组小鼠外,将0.2 mL(1×10^(10)个/L)肿瘤细胞接种于各组小鼠腋窝皮下。ZD组和HD组给予0.5 m L生理盐水灌胃,6小时后给予等体积蒸馏水,1次/d;CP组0.5mL生理盐水灌胃,6小时后腹腔注射环磷酰胺20 mg/(kg·d);WCPP-G、WCPP-Z、WCP-D组分别给予高[400 mg/(kg·d)]、中[200 mg/(kg·d)]、低[100 mg/(kg·d)]浓度0.5 mL党参多糖水溶液灌胃,6小时后腹腔注射0.5 mL生理盐水;WCPP-G、WCPP-Z、WCP-D联合CP组分别给予高、中、低浓度0.5 m L党参多糖水溶液灌胃,6小时后腹腔注射环磷酰胺20 mg/(kg·d)。20天后计算抑瘤率,测定免疫相关指标及血清细胞因子IL-2、IL-6、IL-1β、IL-4、INF-γ、TNF-α的含量。结果:与ZD组比较,HD组IL-2、IL-6、TNF-α、INF-γ水平下降,其中TNF-α变化不明显,差异无统计学意义(P>0.05),其余各项变化明显,差异有统计学意义(P<0.05)。与HD组比较,CP组IL-2、IL-1β、IL-6、IL-4、TNF-α水平降低,其中INF-γ、IL-2水平变化不明显,差异无统计学意义(P>0.05),其余各项变化明显,差异有统计学意义(P<0.05);IL-2、IL-6、IL-1β、IL-4、TNF-α、INF-γ水平各剂量WCPP组及其联合CP组均显著增高,差异有统计学意义(P<0.05)。与HD组及CP组比较,WCPP-G、Z组及各剂量WCPP联合CP组IL-2、IL-6水平变化明显差异有统计学意义(P<0.05),各剂量WCPP组及其联合CP组IL-1β和TNF-α水平均有明显变化,差异有统计学意义(P<0.05)。与CP组比较,WCPP-D组IL-2水平变化明显,差异有统计学意义(P<0.05);WCPP-Z、WCPP-D组IL-4水平变化明显,差异有统计学意义(P<0.05)。与HD组比较,各剂量WCPP组及其联合CP组IL-4和INF-γ水平变化明显,差异有统计学意义(P<0.05)。WCPP各组的抑瘤率均低于CP组;WCPP-G、WCPP-Z、WCP-D+CP组的抑瘤率高于CP组。结论:纹党参多糖能增强环磷酰胺的抗小鼠S180肿瘤作用,这可能与其能提高荷瘤小鼠外周血IL-2水平,降低IL-4水平逆转Th1/Th2漂移,促进免疫细胞的活化和增殖,激活免疫细胞对瘤细胞的特异性和非特异性杀伤有关。

hbstrt^g Objective： To study the synergy between the polysaccharide extracted from WenXian DangShen [Codonopsis pilosula. Var . modesta （Nannf） L. T. shen] and cyclophosphamide fighting against tumor and its mech- anism. Methods： All 135 mice were randomized into nine groups： normal control group （ZD group）, cancer-beating control group （HD group）, cyclophosphamide group（CP group）, the treatment groups ofhigh（WCPP-G group）, mod-erate（WCPP-Z group） and low（WCPP-D group） doses of the polysaccharide extracted from WenXian DangShen, and WCPP-G, WCPP-Z and WCPP-D combined with CP groups, 15 mice each group. Except the mice in ZD group, 0.2mL（lxl01~/L） tumor cells were transplanted under the skin of the armpit of the mice in different groups. ZD group and HD groups were given with intragastric administration of 0.5mL physiological saline, and the distilled water in the same amount in six hours, once per day; CP group accepted intragastric administration of 0.5mL physiological saline, and peritoneal injection of cyclophosphamide 20 mg/ （kg＇d） in six hours; WCPP-G, WCPP-Z and WWCP-D groups accepted intragastric administration ofpolysaccharide aqueous solution in high [400 mg/ （kg·d）], moderate [200 mg/（kg·d）] and low [100 mg/（kg·d）] concentrations, and peritoneal injection of 0.5mL physiological saline in six hours; WCPP-G, WCPP-Z and WWCP-D combined with CP groups received 0.5mL polysaccharide aqueous so- lution in high, moderate and low concentrations by lavage respectively, and peritoneal injection of cyclophos- phamide 20mg/ （kg·d） in six hours; tumor inhibition rate was calculated in 20 days, the contents of immune-related indexes, serum cytokines including IL-2, IL-6, IL- 1/3, IL-4, INF-T and TNF-a were detected. Results： Compared with ZD group, the levels of IL-2, IL-6, INF-T and TNF-a decreased, while the changes of TNF-a changed indistinctly in HD group （P〉0.05）, and others changed evidently （P〈0.05）. Compared with HD group, the levels oflL-2, IL-1β, IL-6, IL-4 and TNF-a lowered in CP group, while the levels of INF-T and IL-2 changed insignificantly （P〉0.05）, others changes obviously （P〈0.05）; the levels oflL-2, IL-6, IL-1β, IL-4, TNF-a and INF-T rose evidently in WCPP groups in different doses and WCPP combine with CP groups （P〈0.05）. Compared with HD group and CP group, the levels of IL-2 and IL-6 changed significantly in WCPP-G, Z group and WCPP combined with CP groups in dif- ferent doses （P〈 0.05）. The levels of IL-113 and TNF-a showed obvious changes in WCPP groups in different doses and WCPP combined with CP groups （P〈0.05）. Compared with CP group, the levels of IL-2 changed notably in WCPP-D group （P〈0.05）; the levels oflL-4 changed notably in WCPP-Z and WCPP-D groups （P〈0.05）. Com- pared with HD group, the levels of IL-4 and INF-T changed apparently in WCPP groups in different doses and WCPP combined with CP groups （P〈0.05）. WCPP groups were lower than CP group in tumor inhibition rate; WCPP-G, WCPP-Z and WCPP-D groups were higher than CP group in tumor inhibition rate. Conclusion： The polysaccharide extracted from WenXian DangShen could enhance anti-tumor effects of cyclophosphamide of the mice, which might be related to improving the levels of IL-2 in peripheral blood of tumor-bearing mice, decreasing the levels of IL-4 to reverse Th1/Th2 shifting, promoting the activation and proliferation of immunological cells, arousing immunological cells＇ specific and nonspecific killings to tumor cells.