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首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >Ursodeoxycholic acid treatment in a rat model of cancer cachexia
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Ursodeoxycholic acid treatment in a rat model of cancer cachexia

机译：熊去氧胆酸治疗癌症恶病质的大鼠模型

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BackgroundCancer cachexia is characterized by loss of both adipose and skeletal muscle tissue and by an increased production of proinflammatory cytokines. Ursodeoxycholic acid (UDCA), a bile acid used for centuries in the treatment of liver disease, is known to confer anti-inflammatory and anti-apoptotic effects as well as beneficial effects on mitochondrial integrity and cell signaling. We hypothesized that UDCA ameliorates the wasting process in the Yoshida hepatoma tumor model. In addition, we sought to establish if UDCA exerts beneficial effects on survival in this model.Methods and resultsForty-seven male rats were inoculated intraperitoneally with 108 Yoshida hepatoma AH-130 cells and treated with placebo or one of two different doses of UDCA, 25 or 100?mg/kg daily. Body weight, body composition, and activity indicators were measured over the course of study up to day?16. UDCA treatment had no effect on tumor growth, loss of body weight, and loss of fat mass. Compared with placebo, low-dose UDCA improved tissue loss in the lung (p?=?0.022) and tended to reduce tissue loss in brown adipocytes (p?=?0.06), gastrocnemius muscle (p?=?0.06), extensor digitorum longus muscle (p?=?0.09), and soleus muscle (p?=?0.07). Compared with placebo, high-dose UDCA tended to reduce the loss of lean body mass (p?=?0.06), lung tissue (p?=?0.1), white adipose tissue (p?=?0.11), and gastrocnemius muscle (p?=?0.11). The activity and food intake were not altered in tumor-bearing rats by either dose of UDCA. Both doses tended to decrease the mortality rate in tumor-bearing rats, (hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.17–1.04; p?=?0.061 for low-dose UDCA; HR, 0.44; 95% CI, 0.18–1.05; p?=?0.065 for high-dose UDCA).ConclusionUDCA treatment in the Yoshida hepatoma model showed a trend towards attenuation of tissue loss in animals with progressive weight loss in cancer cachexia. Tumor growth and activity indicators were not altered. Both doses of UDCA tended to reduce the mortality rates in tumor-bearing animals. Larger studies with longer follow-up are required to verify these findings.
机译：背景癌症恶病质的特征在于脂肪和骨骼肌组织的缺失以及促炎性细胞因子的产生增加。熊去氧胆酸（UDCA）是一种用于治疗肝脏疾病的胆汁酸，已有数百年历史，可赋予抗炎和抗凋亡作用，并对线粒体完整性和细胞信号传导产生有益作用。我们假设UDCA改善了吉田肝癌肿瘤模型中的浪费过程。此外，我们试图确定UDCA是否在该模型中对生存产生有益的作用。方法和结果47只雄性大鼠腹膜内接种108株吉田肝癌AH-130细胞，并用安慰剂或两种不同剂量的UDCA治疗25或每天100？mg / kg。在研究过程中一直测量体重，身体组成和活动指标，直到第16天。 UDCA治疗对肿瘤生长，体重减轻和脂肪量减少没有影响。与安慰剂相比，低剂量UDCA改善了肺部组织损失（p？=？0.022），并倾向于减少褐色脂肪细胞（p？=？0.06），腓肠肌（p？=？0.06），指趾伸肌的组织损失。比目鱼肌（p = 0.09）和比目鱼肌（p = 0.07）。与安慰剂相比，大剂量UDCA倾向于减少瘦体重（p？=？0.06），肺组织（p？=？0.1），白色脂肪组织（p？=？0.11）和腓肠肌（ p≥0.11）。两种剂量的UDCA都不会改变荷瘤大鼠的活动性和食物摄入量。两种剂量都倾向于降低荷瘤大鼠的死亡率（危险比（HR）为0.42; 95％置信区间（CI）为0.17–1.04;低剂量UDCA p？=？0.061; HR为0.44;低剂量UDCA为p。 95％CI，0.18–1.05;对于大剂量UDCA，p？=？0.065）。结论吉田肝癌模型中的UDCA治疗显示出动物组织减少的趋势，癌症恶病质逐渐减轻。肿瘤生长和活动指标未改变。两种剂量的UDCA都倾向于降低荷瘤动物的死亡率。需要更大的研究和更长的随访来验证这些发现。

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