黄连素改善小鼠结肠腺癌恶病质实验研究

Berberine improves cachexia in mice with colon adenocarcinoma

目的通过小鼠结肠腺癌恶病质模型实验探索传统中药提取物黄连素改善恶病质状态的作用及机制。方法将40只BALB/c小鼠随机分成5组,每组8只。即非荷瘤健康对照组、肿瘤恶病质组、黄连素低剂量干预组、黄连素中剂量干预组、黄连素高剂量干预组,使用小白鼠结肠腺癌细胞株CT-26皮下注射BALB/c小鼠,构建荷瘤小鼠肿瘤恶病质模型。黄连素低、中、高剂量干预组小鼠分别给予黄连素12.5 mg/(kg·d)、25 mg/(kg·d)、50mg/(kg·d)灌胃,连续15天。健康对照组、肿瘤恶病质组给予等量生理盐水灌胃。观察低、中、高剂量黄连素对恶病质小鼠的体质量、摄食量、饮水量以及血清中三酰甘油、血糖及总蛋白、白蛋白水平的影响,并比较各组肿瘤组织炎性细胞因子白细胞介素1(interleukin-1,IL-1)、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平以及肝、肾组织形态。观察不同剂量黄连素纠正恶病质的疗效及对肝肾的保护作用。结果与肿瘤恶病质组比较,黄连素干预各组能抑制癌症恶病质小鼠体质量下降,增加小鼠的摄食量、饮水量(均P<0.05);可升高血中总蛋白、白蛋白、血糖浓度,降低血清中三酰甘油的异常升高(均P<0.05);可降低肿瘤组织中的IL-1、IL-6及TNF-α表达水平(均P<0.05);可改善肝、肾组织形态。结论黄连素能有效改善小鼠结肠腺癌恶病质状态,以黄连素中、高剂量组疗效更佳,其机制可能与其有效降低细胞因子(IL-1、IL-6及TNF-α)表达相关。

Objective To investigate the effects of berberine on cancer cachexia in mice with colon adenocarcinoma.Methods Forty BALB/c mice were evenly divided into 5 groups randomly：control group,tumor-bearing group,tumor-bearing group with low-dose berberine [12.5 mg/（kg · d） ],tumor-bearing group with medium-dose berberine[25 mg/（kg·d） ],tumor-bearing group with high-dose berberine [50 mg/（kg·d） ].Cancer cachectic model was induced by inoculation of mice colon adenocarcinoma CT-26 cells in BALB/c mice.The body weight,food and water intake were observed.Total protein,albumin,glucose,triglycerides,interleukin-1（IL-1）,IL-6,tumor necrosis factor-α（TNF-α） were measured.Tissue morphology and apoptotic index of liver and kidney were examined.Results Compared with tumor-bearing group,tumor-bearing group with berberine showed reduced weight loss and increased food and water intake（all P 〈 0.05）.It also showed increased concentration of total protein,albumin and glucose and a decrease of the abnormal rise of triglycerides（all P 〈 0.05）.Berberine decreased IL-1,IL-6,TNF-α levels（all P 〈 0.05）,and reduced the apoptosis of liver and kidney cells.Conclusion Berberine can improve cancer-induced cachexia in mice with colon adenocarcinoma,which may be associated with its effects on the down-regulation of cytokines IL-1,IL-6 and TNF-α.