目的 探讨蝎毒多肽提取物(PESV)对5-Fu干预H₂₂荷瘤小鼠免疫功能的影响。方法 Balb/c小鼠随机分为对照组、模型组、化疗组及PESV高、低剂量组,模型组接种H₂₂肝癌,化疗组ip 20 mg/kg 5-Fu,PESV组化疗同时ig 40、10 mg/kgPESV,连续干预28 d后处死,计算瘤质量、抑瘤率、脾脏指数和胸腺指数。采用鸡红细胞吞噬实验检测H₂₂荷瘤小鼠腹腔巨噬细胞吞噬功能;流式细胞术检测小鼠脾细胞中T细胞亚群、NK细胞和NKT细胞的变化;采用ELISA法检测小鼠外周血中IFN-γ和IL-4的分泌水平。结果 与化疗组比较,PESV高剂量组瘤质量明显减轻(P < 0.05);低、高剂量组的脾脏指数、高剂量组胸腺指数、腹腔巨噬细胞吞噬率和吞噬指数、高剂量组CD4⁺T/CD8⁺T值及高、低剂量组NK/NKT细胞均显著升高(P < 0.05、0.01、0.001)。与化疗组比较,PESV高、低剂量组小鼠血清中IFN-γ水平明显增高,IL-4水平显著降低(P < 0.05、0.01)。结论 PESV可逆转5-Fu干预H₂₂荷瘤小鼠导致的免疫抑制作用。

Objective To study effects of polypeptide extract from scorpion venom (PESV) on immunological function of H₂₂ hepatocarcinoma-bearing mice intervened by 5-Fu. Methods After being inoculated with hepatocarcinoma (H₂₂), Balb/c mice were divided into control group, tumor-bearing group, chemotherapy group, high- and low-dose 5-Fu in combination with PESV groups. All of the mice were put to death after consecutive intervention for 28 d, then to calculate tumor weight, tumor inhibition rate, spleen index, and thymus index. Phagocytizing chicken red blood cell test was used to detect abdominal macrophage phagocytosis in H₂₂ hepatocarcinoma-bearing mice. T cell subsets, changes of NK and NKT cells in spleen cells were detected using flow cytometry. The secretion levels of IFN-γ and IL-4 in peripheral blood were detected by ELISA. Results Compared with the chemotherapy group, tumor weights of the 5-Fu in combination with PESV groups were significantly decreased (P < 0.05), and spleen index and thymus index in this group were significantly increased (P < 0.05). At the same time, phagocytic ratio and index of macrophage cell in abdominal cavity in this group were significantly higher than those in the chemotherapy group (P < 0.05). Values of CD4⁺T/CD8⁺T cells in the high-dose 5-Fu in combination with PESV group were significantly higher than that in the chemotherapy group (P < 0.01). Levels of NK/NKT cells in the high- and low-dose 5-Fu in combination with PESV groups were significantly higher than those of model group (P < 0.01 and 0.05, respectively). Compared with the chemotherapy group, content of serum IFN-γ was significantly higher, while content of serum IL-4 decreased significantly in the high- and low-dose 5-Fu in combination with PESV groups (P < 0.01 and 0.05, respectively). Conclusion PESV could reverse immunosuppression of H₂₂ hepatocarcinoma-bearing mice caused by 5-Fu intervention.

国家自然科学基金(81303077,81403150);山东省中医药科技发展计划项目(2015-323)