摘要
目的:探索加味健脾解毒方对腹水型肝癌小鼠恶病质及IL-1a、IL-6、TNF-a和泛素蛋白酶体途径的作用。方法:60只C57BL/6小鼠随机分为正常对照组,荷瘤模型组,中药低浓度组、中药高浓度组、醋酸甲羟孕酮联合吲哚美辛组5组。H22肝癌细胞株腹腔注射建立小鼠腹水型肝癌恶病质模型,记录小鼠体质量、摄食量、腓肠肌重量等恶液质指标;检测腹水IL-1a、IL-6、TNF-a水平;检测腓肠肌Mu-RF1、Atrogin1蛋白及mRNA表达。结果:与模型组比,高、低浓度加味健脾解毒方明显减缓小鼠体质量及腹水增长(P<0.05),降低小鼠腓肠肌消耗(P<0.01),提高去腹水体质量(P<0.01)和摄食量(P<0.05);降低腹水IL-1a、IL-6、TNF-a水平(P<0.01);降低Mu-RF1、Atrogin1蛋白及mRNA表达(P<0.01)。上述指标高浓度中药优于低浓度中药(P<0.05);高浓度中药与醋酸甲羟孕酮联合吲哚美辛组相当(P>0.05)。腹水量和肝脏指数高浓度中药优于醋酸甲羟孕酮联合吲哚美辛组(P<0.05)。结论:加味健脾解毒方可延缓腹水肝癌小鼠的恶病质进展,可能与其降低IL-1、IL-6、TNF-a水平及抑制泛素蛋白酶体途径过度激活有关。
Objective： To explore the effect of modified Jianpi Jiedu Recipe（ MJPJD） on cachexia of ascites hepatoma mice and IL-1a,IL-6,TNF-α and ubiquitin proteasome pathways. Methods： 60 C57 BL /6 mice were randomly divided into normal control group,tumor model group,MJPJD low and high concentrations groups and medroxyprogesterone acetate combined with indomethacin group. Mice cachexia model was established by intraperitoneal injection of H22 hepatoma cell line. We recorded cachexia conditions such as body weight,food intake,gastrocnemius weight and so on. ELISA was used to detect IL-1a,IL-6 and TNF-α levels in ascites. Western Blot and RT-PCR detected protein and mRNA of Mu-RF1 and Atrogin1 in mice gastrocnemius muscle. Results： Compared with model group,the high and low concentrations of MJPJD groups can effectively control the body weight and growth of mice ascites（ P 〈0. 05）,decrease mice gastrocnemius muscle consumption significantly（ P〈 0. 01）,maintain the net weight（ P 〈0. 01）,increase the food intake of mice（ P 〈0. 05） and can significantly lower the levels of IL-1a,IL-6 and TNF-α（ P〈 0. 01） and significantly reduce the Mu-RF1,Atrogin1 protein and mRNA expressions（ P 〈0. 01）. These indexes above of high concentration MJPJD group were better than that of low concentration MJPJD group（ P 〈0. 05） and similar to medroxyprogesterone acetate combined with indomethacin group（ P〈 0. 05）. Ascites weight and liver index of high concentration MJPJD group were better than that of medroxyprogesterone acetate combined with indomethacin group（ P〉 0. 05）. Conclusion： The modified Jianpi Jiedu Recipe might delay the cachexia progress of cachexia of liver cancer ascites mice model and its mechanism is associated with reducing IL-1,IL-6 and TNF-α levels and the inhibition of the over activation of ubiquitin proteasome pathway.
出处
《中华中医药学刊》
CAS
北大核心
2015年第12期2830-2835,I0018-I0020,共9页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金青年科学基金项目(81102581)
