黄芪多糖对 Lewis 肺癌小鼠细胞因子及顺铂所致免疫功能低下的影响

摘要

Objective To observe the effects of Astragalus polysaccharide ( APS) on tumor growth, cytokine and immune function impairment induced by cisplatin ( DDP) in mice bearing Lewis lung cancer.Methods A total of 90 mice were used in this study:10 for blank control group, and 80 mice with transplanted Lewis lung cancer were randomly divided into 8 groups:model control group (physiological saline), positive control group treated with DDP (6 mg/kg), low dose APS (50 mg/kg), moderate dose APS (100 mg/kg) and high dose APS (200 mg/kg) groups and three combinations of APS+DDP groups ( the same three APS levels with half dose of DDP, respectively) .0.3 mL of the drugs was intraper-itoneally injected to the mice, respectively, on the second day after moldeling.DDP was injected once a week and other drugs were injected once per day for consecutive 20 days.On the 21st day, blood samples were collected and serum levels of cytokine IL-2, IL-6, IL-12 and TNF-αwere determined by ELISA, and the tumor inhibition rate and immune organ in-dexes were assessed.Results The tumor inhibition rates of the positive control, low, moderate and high dose APS groups and three combinations of APS+DDP groups of mice bearing Lewis lung carcinoma were 49.30%, 17.21%, 39.68%, 17.21%, 51.02%, 57.21%and 65.11%, respectively.Compared with the model group, P<0.05 or P<0.01, and compared the three combination groups with the DDP group, P<0.05.Compared with the blank control group, the spleen index was significantly increased in the moderate and high dose APS groups and the three combinations of APS +DDP groups.There was a significant difference between the spleen indexes of the model control group, and the spleen indexes of high dose APS and the combination with high dose APS groups were significantly higher than that of the model control group (P<0.05).Compared with the DDP group, APS in various doses and combinations increased the thymus index and spleen index.Conclusions APS can improve the levels of cytokine IL -2, IL-6, IL-12 and TNF-αin mice bearing Lewis lung cancer, enhance the immune function impairment induced by DDP, has certain protective effect on the immune organs, and inhibit the growth of Lewis lung cancer in mice.When APS is used in combination with a half-dose of DDP, APS enhanced the inhibition of tumor growth.This mechanism may be related to the enhanced body immune function.Our results indicate that APS enhances the therapeutic effect of DDP and reduces its toxicity, therefore, may have potential application value in future treatment of solid tumors.%目的：观察黄芪多糖（ APS）对小鼠Lewis肺癌移植瘤生长、细胞因子及顺铂（ DDP）所致免疫功能低下的影响。方法90只小鼠，设空白对照组10只，余80只依次造模为荷瘤小鼠，并随机分为8组：模型组（等体积生理盐水），顺铂阳性对照组（6 mg/kg DDP），APS低（50 mg/kg）、中（100 mg/kg）、高剂量（200 mg/kg）组，联合用药低、中、高剂量组（ DDP剂量减半， APS各剂量同上），于造模次日起各组分别腹腔注射等体积的药物0.3 mL。DDP每周一次，其余药物每天1次，连续20d。于第21天取血清采用ELISA法测定细胞因子IL-2、IL-6、IL-12、TNF-α的水平，并观察各组抑瘤率及免疫器官指数。结果 DDP、APS低、中、高剂量及联合用药低、中、高剂量组对小鼠Lewis肺癌移植瘤的抑瘤率分别为49.30％、17.21％、39.68％、42.98％、51.02％、57.21％、65.11％（与模型组比较P ＜0.05或0.01；联合用药组与DDP组比较P＜0.05）。与空白对照组比较，APS中、高剂量组和联合用药组脾脏指数显著升高；与模型组比较，APS高剂量和联合高剂量脾脏指数差异有显著性（ P＜0.05）；与DDP组比较，APS各剂量和联合用药组小鼠胸腺指数和脾脏指数均升高。结论 APS能提高Lewis 肺癌小鼠血清中细胞因子IL-2、IL-6、IL-12、TNF-α的水平；增强DDP所致免疫功能低下小鼠的免疫功能，对免疫器官有一定的保护作用；能抑制小鼠Lewis肺癌细胞的生长，在与DDP减半量联合使用时可使DDP抑瘤作用增强，且其机制可能与增强机体的免疫功能有关，说明APS对DDP有一定的增效减毒作用。此项研究在实体瘤的治疗中有潜在的应用前景。