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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 Jiawei Jianpi Jiedu Fang on cachexia, IL-1a, IL-6, TNF-a and ubiquitin-proteasome pathways in mice with ascites hepatocellular carcinoma. Methods: Sixty C57BL / 6 mice were randomly divided into normal control group, tumor-bearing model group, low concentration Chinese medicine group, high concentration Chinese medicine group, medroxyprogesterone acetate combined with indomethacin group. H22 hepatocellular carcinoma cell lines were established by intraperitoneal injection of mouse model of ascites hepatocarcinoma cachexia mice body weight, food intake, gastrocnemius weight and other indicators of cortisol; ascites IL-1a, IL-6, TNF-a levels were measured gastrocnemius Mu -RF1, Atrogin1 protein and mRNA expression. Results: Compared with the model group, the Jianpi Jiedu Decoction of high and low concentration obviously slowed the body weight and the ascites growth (P <0.05), reduced the consumption of gastrocnemius (P <0.01), and improved the quality of ascites (P < 0.01) and food intake (P <0.05). The levels of IL-1a, IL-6 and TNF-a in ascites were decreased (P <0.01), and the expressions of Mu-RF1 and Atrogin1 were decreased. The above-mentioned indicators of high concentration of Chinese medicine is better than the low concentration of traditional Chinese medicine (P <0.05); high concentration of Chinese medicine and medroxyprogesterone acetate combined indomethacin group (P> 0.05). Ascites and liver index of high concentration of Chinese medicine is superior to medroxyprogesterone acetate indomethacin group (P <0.05). Conclusion: Modified Jianpi Jiedu can delay the progression of cachexia in mice with ascitic hepatocellular carcinoma, which may be related to the decrease of IL-1, IL-6, TNF-a levels and the inhibition of ubiquitin proteasome pathway over-activation.