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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12 d,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。
Objective To study the inhibitory effect of curcumin on the tumor of H22 tumor-bearing mice and its possible mechanism by means of monascus fungi transformation of curcumin, and to lay a foundation for further screening new and effective curcumin antitumor drugs. Methods Kunming mice were inoculated with H22 cells under the armpit to induce tumor-bearing mice model, curcumin-producing cells of Curviruses, cell control group and substrate control group. The H22 cells were inoculated with high, medium and low doses (2, 1, 0.5 g / kg). The normal control group, tumor-bearing model group and cyclophosphamide control group were established. The rats were sacrificed 12 days after the last administration, blood was taken from the rats for 12 days after the last administration to determine the levels of tumor necrosis factor (TNF-α) and interleukin-2 (IL-2) ; Take the liver, thymus, spleen, weighing calculation of organ index. Results The inhibitory effects of curcumin in high, medium and low dose groups were 37.08%, 48.91% and 26.55%, respectively, which were significantly higher than those of the control group and the substrate control group at the same dose, but not higher than that of the control group Amide control group. Mice index showed that each dose of the transformed product was higher than the tumor-bearing model group, while there was no significant difference between the control group and the substrate control group and the tumor-bearing model group (P> 0.05). The levels of TNF-α and IL-2 in serum of curcumin-transformed products were higher than that of tumor-bearing model group and higher than those of control group and substrate control group (P <0.05). CONCLUSION: Curcumin can inhibit the growth of the tumor after transformation, increase the organ index of the major immune organs and improve the immune function of the body. Curcumin may inhibit tumor growth by directly killing the tumor by increasing the level of TNF-α in vivo, or increasing the level of IL-2 to enhance the T-cell immune response.