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姜黄素转化产物抗肿瘤的研究

     

摘要

Objective To study the inhibitory effect of total products of curcumin ( Cur) biotransformation on tumor and possible metabolism in H22 tumor-bearing mice after microbial transformation of Cur by Monascus purpureus, and lay a foundation for screening new and efficient curcumin medications of anti-tumor. Methods Kunming mice were inoculated with H22 cells for establishing tumor-bearing mouse model. All mice were divided into the group of Cur transformation products of Monascus purpureus (Cur group) , Monascus control group ( Monascus group) , substrate control group ( substrate group) , normal control group (normal group) , tumor-bearing model group (model group) and cyclophosphamide control group ( CTX group). The trans-product group, Monascus group and substrate group were, respectively, intervened with corresponding drugs in high, medium and low doses for 12 days. After the last time administration of drugs for 12 hours, the blood samples were collected for separating serum and detecting the levels of tumor necrosis factor-α ( TNF-α) and interleukin-2 (IL-2) . The tumor was taken for weighing and calculating tumor inhibitory rate. The liver, thymus and spleen were taken for weighing and calculating organ indexes. Results The tumor inhibitory rate in high-dose, mid-dose and low-dose Cur groups was respectively 37. 08% , 48. 91% and 26.55% , which was significantly higher than that in high-dose, mid-dose and low-dose Monascus groups and high-dose, mid-dose and low-dose substrategroups, but not higher than that in CTX group. The organ indexes were higher in high-dose, mid-dose and low-dose Cur groups than those in model group, and those in Monascus groups and substrate groups were not different compared with model group (P >0. 05). The levels of TNF-a and IL-2 were higher in high-dose, mid-dose and low-dose Cur groups than those in model group, Monascus groups and substrate groups (P<0.05). Conclusion Cur, after biotransformation, has higher inhibitory effect on tumor, and can increase the organ indexes of main immune organs and improve body's immunity. It may inhibit tumor through rising TNF-a level to kill tumor directly or promoting IL-2 level to enhance immune response of T cells.%目的 利用红曲霉菌对姜黄素进行微生物转化,研究姜黄素转化总产物对H22荷瘤小鼠肿瘤的抑制作用及其可能机理,为进一步筛选新型高效的姜黄素类抗肿瘤新药奠定基础.方法 昆明种小鼠腋下接种H22细胞造成荷瘤小鼠模型,姜黄素红曲霉菌转化产物组、菌体对照组、底物对照组,分别以高、中、低剂量(2、1、0.5 g/kg)进行干预治疗;设立正常对照组、荷瘤模型组、环磷酰胺对照组.连续治疗12d,于末次给药后12 h,取血分离血清,测定肿瘤坏死因子(TNF-α)、白细胞介素-2 (IL-2);剥取肿瘤,称重,计算抑瘤率;取肝脏、胸腺、脾脏,称重计算脏器指数.结果 姜黄素转化产物高、中、低剂量组的抑瘤作用分别为37.08%、48.91%、26.55%,明显高于同剂量的菌体对照组和底物对照组,但并未高于环磷酰胺对照组.小鼠脏器指数结果显示转化产物各剂量组均高于荷瘤模型组,而菌体对照组、底物对照组与荷瘤模型组比较没有显著差异(P>0.05).姜黄素转化产物各剂量组血清TNF-α和IL-2水平均高于荷瘤模型组,且高于菌体对照组及底物对照组,并有显著差异(P<0.05).结论 姜黄素转化后对肿瘤的抑制作用增强,能够增加机体主要免疫器官的脏器指数,提高机体的免疫功能.姜黄素转化后可能是通过提高体内TNF-α水平来直接杀伤肿瘤,或提高IL-2水平增强T细胞免疫应答来抑制肿瘤生长.

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