目的 探討蝎毒多肽提取物(PESV)對(duì)5-Fu干預(yù)H₂₂荷瘤小鼠免疫功能的影響。方法 Balb/c小鼠隨機(jī)分為對(duì)照組、模型組、化療組及PESV高、低劑量組,模型組接種H₂₂肝癌,化療組ip 20 mg/kg 5-Fu,PESV組化療同時(shí)ig 40、10 mg/kgPESV,連續(xù)干預(yù)28 d后處死,計(jì)算瘤質(zhì)量、抑瘤率、脾臟指數(shù)和胸腺指數(shù)。采用雞紅細(xì)胞吞噬實(shí)驗(yàn)檢測(cè)H₂₂荷瘤小鼠腹腔巨噬細(xì)胞吞噬功能;流式細(xì)胞術(shù)檢測(cè)小鼠脾細(xì)胞中T細(xì)胞亞群、NK細(xì)胞和NKT細(xì)胞的變化;采用ELISA法檢測(cè)小鼠外周血中IFN-γ和IL-4的分泌水平。結(jié)果 與化療組比較,PESV高劑量組瘤質(zhì)量明顯減輕(P < 0.05);低、高劑量組的脾臟指數(shù)、高劑量組胸腺指數(shù)、腹腔巨噬細(xì)胞吞噬率和吞噬指數(shù)、高劑量組CD4⁺T/CD8⁺T值及高、低劑量組NK/NKT細(xì)胞均顯著升高(P < 0.05、0.01、0.001)。與化療組比較,PESV高、低劑量組小鼠血清中IFN-γ水平明顯增高,IL-4水平顯著降低(P < 0.05、0.01)。結(jié)論 PESV可逆轉(zhuǎn)5-Fu干預(yù)H₂₂荷瘤小鼠導(dǎo)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.

國(guó)家自然科學(xué)基金(81303077,81403150);山東省中醫(yī)藥科技發(fā)展計(jì)劃項(xiàng)目(2015-323)