注射用免疫核糖核酸Ⅱ的免疫调节及对顺铂的增效减毒作用

Effects of BP on modulating sensitivity and toxicity of cisplatin and regulating immune function in S180 tumor-bearing mice

目的探讨注射用免疫核糖核酸Ⅱ(BP素)对顺铂(DDP)的增效减毒作用及对S180荷瘤小鼠的免疫调节作用。方法建立小鼠S180皮下移植瘤模型,随机分组,采用腹腔注射给药,连续给药10 d,通过白细胞(WBC)计数、骨髓有核细胞计数,取肿瘤、胸腺、脾脏称重,计算抑瘤率、胸腺指数、脾脏指数以及MTT法检测刀豆蛋白A(Con A)诱导的小鼠脾脏T淋巴细胞增殖,观察BP素对顺铂的增效减毒作用。通过ELISA法检测血清中的IL-1β、IL-6、TNF-α水平,通过腹腔巨噬细胞对鸡红细胞吞噬率的测定评价BP素对S180荷瘤小鼠的免疫调节作用。结果 BP素与DDP联合应用可显著提高DDP对S180荷瘤小鼠的抗肿瘤作用(P<0.01),明显改善DDP化疗所致的脾脏指数下降,外周血WBC数、骨髓有核细胞数的减少及脾脏T淋巴细胞增殖抑制等毒副作用(P<0.01或P<0.05);单用BP素可显著降低荷瘤小鼠血清中的IL-1β、IL-6、TNF-α水平(P<0.01或P<0.05),提高腹腔巨噬细胞吞噬鸡红细胞的吞噬率(P<0.01)。结论 BP素对DDP具有增效减毒作用,并对S180荷瘤小鼠具有免疫调节作用。

Objective To investigate the effects of BP on modulating sensitivity and toxicity of cisplatin and regulating immune function in S180 tumor-bearing mice. Method The S180 tumor-bearing mice model was established and consecutively administrated with BP alone（12.5, 50 mg/kg, i.p.）, DDP alone（2 mg/kg, i.p.） or BP ＋ DDP（25, 50, 100 mg/kg ＋ 2 mg/kg） for 10 days. To evaluate the synergistic antitumor and attenuated effects of BP combined with DDP, peripheral white blood cells（WBC） and bone marrow nucleated cells were calculated. Also tumor, thymus and spleen were weighed and tumor inhibition rate, thymus and spleen index were measured, and Con A-induced T cells proliferation was also conducted by MTT assay. To evaluate the immune regulatory effect of BP, serum levels of IL-1β, IL-6 and TNF-α were detected by ELISA and phagocytic ratio of peritoneal macrophages was calculated. Result BP combined with DDP could significantly enhance the antitumor effect（P〈0.01）. BP significantly reversed DDP-induced reduction of spleen index, WBC and bone marrow nucleated cells（P〈0.01 or P〈0.05）. BP combined with DDP could also significantly improve T cells proliferation（P〈0.01 or P〈0.05）. Moreover, BP could obviously decrease levels of IL-1β, IL-6 and TNF-α in serum（P〈0.01 or P〈0.05） and improve the phagocytic ratio（P〈0.01）. Conclusion BP combined with DDP has synergistic antitumor effect and attenuated DDP-induced toxic effects in S180 tumor-bearing mice. Moreover, BP has immunomodulatory effects in S180 tumor-bearing mice.