精氨酸双糖苷对环磷酰胺致免疫抑制小鼠免疫功能的影响

THE PROTECTIVE EFFECT OF ARGINYL-FRUCTOSYL-GLUCOSE AGAINST CYCLOPHOSPHAMIDE-INDUCED IMMUNOSUPPRESSION IN MICE

目的研究精氨酸双糖苷（arginyl-fructosyl-glucose,AFG）对环磷酰胺（CTX）诱导的免疫抑制小鼠免疫功能的影响。方法取BALB/C小鼠脾淋巴细胞,以不同浓度AFG（1,2,4,6,8,10μg/ml）刺激淋巴细胞的体外转化。另取ICR小鼠80只,随机分为8组：正常对照组（N）和免疫抑制模型组（M）给予生理盐水,免疫抑制给予AFG组：M＋AFG-H,M＋AFG-M和M＋AFG-L,三组分别给予50,30,10 mg/kg bw AFG,正常给AFG组：N＋AFG-H,N＋AFG-M和N＋AFG-L三组对应给予高中低50,30,10 mg/kg bw AFG。免疫抑制对照组及M＋AFG-H,M＋AFG-M,M＋AFG-L在第1、2、3、9、16、23、30 d小鼠腹腔注射CTX 80mg/kg。测定AFG对BALB/C小鼠淋巴细胞体外转化的影响。30 d后处死ICR小鼠,测定胸腺指数和脾脏指数。AFG对脾淋巴细胞自然转化,T细胞转化,B细胞转化的影响,以及肿瘤坏死因子-α（TNF-α）及白细胞介素-2（IL-2）含量。结果高中低剂量AFG均能显著提高免疫抑制小鼠的脾脏指数和胸腺指数（P〈0.01,P〈0.05=。AFG对于体外脾淋巴细胞转化的促进作用随浓度的增大而增大,加药剂量为1-10μg/ml时,转化率呈浓度依赖性。AFG中剂量能显著促进免疫抑制小鼠脾细胞的自然转化（P〈0.05）,而AFG低剂量能极显著促进脾淋巴细胞的自然转化（P〈0.01）;高剂量AFG对于免疫抑制小鼠T淋巴细胞的转化具有显著性（P〈0.05）;高中低剂量AFG均能显著促进免疫抑制小鼠B淋巴细胞的转化（P〈0.01,P〈0.05）。AFG高中低剂量均能显著提高免疫抑制小鼠血清中TNF-α（P〈0.01）,其中高中剂量均能显著增加IL-2含量（P〈0.01,P〈0.05）。结论 AFG具有很强的免疫增强活性并能拮抗CTX的免疫抑制作用。

Objective To evaluate the effect of arginyl-fructosyl-glucose（AFG） on cyclophosphamide（CTX）-induced immunosuppression in mice. Methods Ten BALB/C mice were sacrificed, and the spleen lymphocytes transformation was stimulated with different concentrations of AFG（1, 2, 4, 6, 8, 10 μg/ml）in vitro. Another eighty mice were divided randomly into eight groups with 10 mice in each group：normal control（N） and immunosuppression model（M） received normal saline（NS） solution（0.9%, w/v）. Groups M＋AFG-H, M＋AFG-M and M＋AFG-L received AFG at dosages of 50, 30 and 10 mg/kg bw, respectively; Groups N＋AFG-H, N＋AFG-M and N＋AFG-L also received AFG at dosages of 50, 30 and10 mg/kg bw, respectively. Groups M＋AFG-H, M＋AFG-M and M＋AFG-L were treated with CTX（80 mg/kg bw） on days 1, 2, 3, 9, 16, 23 and 30. The effect of AFG on lymphocytes transformation was determined in vitro. After treatment with AFG for 30 days, the animals were sacrificed, and various immune indices, such as thymus and spleen indices, activity of lymphocyte transformation, tumor necrosis factor-α（TNF-α）and interleukin-2（IL-2） content in serum were measured. Results Thymus and spleen indices were significantly higher in mice treated with different doses of AFG（P〈0.01,P〈0.05）than those in the M group. The function of AFG in promoting spleen lymphocyte transformation in vitro was enhanced with increasing concentration, when administered in the range from 1 to 10 μg/ml, the conversion rate was concentration-dependent. AFG-M could promote spleen lymphocyte transformation significantly（P〈0.05）and the effect of AFG-L on spleen lymphocyte transformation was very significant（P0.01）; T lymphocyte and B lymphocyte were transformed obviously at the high dose of AFG（P〈0.05）, and mice treated with AFG-M and AFG-L were also had a significant（P0.01, P〈0.05）higher conversion rate of B lymphocyte compared with immunosuppression model. ELISA experiments showed that AFG treatment enhanced production of TNF-α（P0.01）,while orally administered AFG-H and AFG-M enhanced production of IL-2（P0.01, P〈0.05）. Conclusion AFG displayed strong immune enhancing activity and a protective effect against CTX-induced immunosuppression.