苦参碱对H_(22)荷瘤小鼠的抑瘤作用及对免疫功能的影响

Antitumor efficacy of matrine and its effect on immune function in H_(22) tumor-bearing mice

目的 研究苦参碱的体内抑瘤效应与荷瘤机体免疫功能的关系 ,初步探讨苦参碱抑瘤作用的免疫学机制。方法 采用 MTT法观察不同剂量苦参碱对荷瘤小鼠外周血淋巴细胞 (PBL )增殖能力的影响 ;采用小鼠 H2 2 肝癌细胞实体瘤模型进行苦参碱的体内抑瘤实验 ,测定肿瘤生长抑制率 (IR) ,观察荷瘤小鼠免疫器官质量和病理学形态的改变 ;EL ISA法检测小鼠血清中白细胞介素 - 2 (IL - 2 )和白细胞介素 - 12 (IL - 12 )水平。结果 高、低剂量苦参碱对小鼠 H2 2 实体瘤生长具有明显抑制作用 ,抑瘤率分别为 6 0 .7%和 6 2 .5 % (P<0 .0 1) ;体外增殖试验显示 ,苦参碱单独作用时 ,对荷瘤小鼠静止 PBL体外增殖的抑制作用较明显 ,但对刀豆蛋白 A (Con A)活化的荷瘤小鼠PBL 的体外增殖反应表现出一定的促进作用 ,随苦参碱质量浓度的增高 ,促进作用随之减弱 ;苦参碱治疗后小鼠的脾脏和胸腺质量减轻 ,其中以脾脏变化更为明显 (P<0 .0 1) ,病理切片显示胸腺皮质变薄 ;苦参碱不能提高荷瘤小鼠血清 IL - 2和 IL - 12水平 (P>0 .0 5 )。结论 苦参碱在体内具有较强的抗肿瘤作用 ,但在体内、体外都表现出一定的免疫抑制作用 ,显示苦参碱的抗肿瘤活性不是通过提高机体的免疫功能来实现的。

Object To investigate the relationship between in vivo antitumor efficacy of matrine and its effect on immune function in H 22 tumor-bearing model mice and discuss the immune mechanism of matrine in inhibiting tumor growth. Methods MTT assay was used to observe the influence of matrine on proliferation of peripheral blood lymphocytes (PBL) stimulated by ConA in vitro from H 22 tumor-bearing mice. H 22 tumor-bearing model mice were applied to evaluate in vivo antitumor efficacy of matrine. The tumor growth inhibitory rate (IR) was calculated. Murine serum IL-2 and IL-12 were detected by means of ELISA assay. Results Matrine had remarkable inhibitory effect on tumor growth in H 22 tumor-bearing model mice. The IR were 60.7% and 62.5% (P<0.01) in the groups treated with low- and high-dose of matrine, respectively. Matrine showed an increasingly inhibitory effect on in vitro proliferation of murine PBL with an elevation of matrine dosage and a lessen SI scores compared with that of control panel when it was prescribed in single, while a combined effect on proliferation of murine PBL activated by ConA observed in MTT assay, and a decreasing inhibitory effect was also found along with the elevation of matrine dosage. The weights of both spleen and thymus of H 22 tumor-bearing model mice treated with matrine became less than that of control panel, and spleen decreased more than thymus gland (P<0.01). Paraffin slice H and E staining revealed thymus cortex became thinner. The increasing of serum IL-2 and IL-12 had not appeared in H 22 tumor-bearing model mice treated with matrine (P>0.05). Conclusion Matrine has marked in vivo antitumor effect, but it can not improve the immune function of H 22 tumor-bearing mice both in vivo and in vitro. This inferred that improving immune function may not be the main mechanism for matrine to exert its antitumor effect.