杨桃根中2-十二烷基-6-甲氧基-2,5-二烯-1,4-环己二酮抗肝癌作用及机制的研究

目的：探讨杨桃根中2-十二烷基-6-甲氧基-2，5-二烯-1，4-环己二酮（DMDD）对裸鼠肝癌的抑瘤作用，并研究其机制。方法：建立人肝癌裸鼠皮下移植瘤模型，48只裸鼠随机分为6个组：DMDD高剂量组，DMDD中剂量组，DMDD低剂量组，多柔比星组，模型组，空白组，每组8只。记录裸鼠体质量和肿瘤大小变化，计算瘤重，抑瘤率，肿瘤指数及脏器指数；检测血常规指标：白细胞（WBC）、红细胞（RBC）、血红蛋白（HGB）和血小板（PLT）；采用酶联免疫法检测裸鼠血清中白介素2（IL-2）和白介素10（IL-10）的含量；免疫组化法检测TLR4，MyD88和NF-κB的蛋白表达水平。结果：DMDD各剂量组及多柔比星组的瘤体质量均小于模型组（P<0.01），DMDD高、中、低剂量组及多柔比星组的抑瘤率分别：66.39%，63.11%，47.33%，49.38%，DMDD各剂量组和多柔比星组的肿瘤指数低于模型组（P<0.01），DMDD各剂量组的脾脏指数低于模型组（P<0.01）；DMDD各剂量组均能升高WBC、HGB和PLT的数量（P<0.01或P<0.05）；DMDD各剂量组能降低的血清中IL-2和IL-10的表达水平（P<0.01或P<0.05）；免疫组化结果显示，DMDD各剂量组均能下调TLR4，MyD88和NF-κB的蛋白表达水平。结论：DMDD具有良好的抗肝癌作用，该作用可能与其能改善裸鼠免疫器官的功能和血常规指标，下调IL-2和IL-10的水平，调控TLR4/MyD88/NF-κB信号通路有关。

Anti-hepatocarcinoma effect and its mechanism of 2-dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione in carambola roots

OBJECTIVE To investigate the anti-tumor effect and mechanism of DMDD on hepatocarcinoma in nude mice. METHODS A subcutaneous xenograft model of human hepatocarcinoma was established. 48 nude mice were randomly divided into six groups: high-dose DMDD group, medium-dose DMDD group, low-dose DMDD group, doxorubicin group, model group, blank group, with 8 mice in each group. Changes in body weight and tumor size in nude mice were recorded. Tumor weight, tumor inhibition rate, tumor index, and organ index were calculated. Blood routine indexes: white blood cell(WBC), red blood cell(RBC), hemoglobin(HGB) and platelet(PLT). Serum levels of interleukin-2(IL-2) and interleukin-10(IL-10) in nude mice were detected by enzyme-linked immunosorbent assay. The expression levels of TLR4, MyD88 and NF-κB were detected by immunohistochemistry.RESULTS The tumor weight of all DMDD groups and doxorubicin group were lower than that of model group(P<0.01). The tumor inhibition rates of all DMDD groups and doxorubicin group were 66.39%, 63.11%, 47.33%, 49.38%, respectively. The tumor index of all DMDD groups and doxorubicin group was lower than that of model group(P<0.01), and the spleen indexes of all DMDD groups was lower than that of model group(P<0.01);the number of WBC, HGB and PLT increased in DMDD group(P<0.01 or P<0.05);the levels of IL-2 and IL-10 in serum decreased in DMDD group(P<0.01 or P<0.05);immunohistochemical results showed that the expression levels of TLR4, MyD88 and NF-κB were down-regulated in all DMDD groups.CONCLUSION DMDD has a great anti-hepatocarcinoma effect, which may be related to the improvement of immune function and blood routine index, down-regulation of IL-2 and IL-10 levels and regulation of TLR4/MyD88/NF-kB signaling pathway in nude mice.