熊果酸对荷骨肉瘤大鼠免疫功能的影响

Effects of ursolic acid on immune function of osteosarcoma rats

目的研究熊果酸对荷骨肉瘤大鼠免疫功能的影响及其机制。方法通过于Wistar大鼠股骨远端骨髓腔中注射接种骨肉瘤UMR106细胞的方法建立荷骨肉瘤大鼠模型并腹腔注射给予不同剂量的熊果酸100、50、25 mg/(kg·d)和顺铂2.5 mg/(kg·d)进行干预治疗,疗程5天。观察大鼠生存状态和肿瘤生长状况;称量瘤体质量并计算抑瘤率,HE染色法观察肿瘤组织形态结构改变,MTT法测定脾淋巴细胞转化率;ELISA法测定血清中白细胞介素-2(interleukin-2,IL-2)和肿瘤坏死因子-α(tumor necrosis factor alpha,TNF-α)含量;流式细胞术检测血液中T淋巴细胞亚群CD4^+、CD8^+百分率并计算CD4^+/CD8^+比值。结果经熊果酸干预治疗5天荷骨肉瘤大鼠饮食状况好转,瘤体缩小、瘤体质量减轻且硬度较差,呈现肿瘤细胞皱缩、组织片状坏死等变化;抑瘤率显著升高,脾淋巴细胞转化率显著升高,血清中IL-2、TNF-α含量显著降低,血液中CD4^+显著升高、CD8^+百分率显著降低,CD4^+/CD8^+比值显著升高,且均具有一定的剂量依赖性。结论熊果酸具有提高荷骨肉瘤大鼠免疫功能的作用,其机制可能与熊果酸能够有效提高脾淋巴细胞转化率,降低IL-2、TNF-α含量以及提高CD4^+百分率、降低CD8^+百分率而提高CD4^+/CD8^+比值有关。

Objective To investigate the effects and mechanism of ursolic acid（ UA） on immune function of osteosarcoma cancer rats. Methods The osteosarcoma cancer rat models were conducted by in-jecting osteosarcoma cancer cell line UMR106 and were treated with UA 100,50,25 mg /（ kg·d） and Cisplatin 2. 5 mg /（ kg·d） by intraperitoneal injection for 5 d. The rats’ general states and tumor growth conditions were observed,the histopathological changes of tumor tissue were observed by HE staining; he tumor weight was detected and inhibition rate was calculated,the spleen lymphocyte transformation rate was detected by MTT,the content of IL-2 and TNF-α in serum were detected,the percentage of CD4~＋,CD8~＋in blood were detected and the ratio of CD4~＋/ CD8~＋was calculated. Results The diet situation of the rats in UA treated groups were improved,tumor were reduced and hardness were less,tumor cell showed shrinkage,tissue necrosis,etc; the tumor inhibition rate were increased; the spleen lymphocyte transformation rate were significantly increased; the content of IL-2 and TNF-α in serum were significantly decreased; the CD4~＋percentage in blood were significantly increased,the CD8~＋percentage was significantly decreased,the ratio of CD4~＋/ CD8~＋in UA treated groups were significantly increased. The effect of the above mentioned effects of UA has a certain dose dependence. Conclusion UA can effectively improve the immune function of osteosarcoma cancer rat; which perhaps related to its effects of increasing the spleen lymphocyte transformation rate,reducing the content of IL-2 and TNF-α,increasing CD4~＋percentages,decreasing CD8~＋percentages and raising the ratio of CD4~＋/ CD8~＋.