实验性癌性恶病质的发生及其干预

The occurrence and therapy of expremental cancer cachexia

目的初步探讨促炎细胞因子IL-6、TNF-α在癌性恶病质(CC)形成中的作用并观察不同剂量吲哚美辛(indomethaein,IN)对CC改善效果。方法将鼠结肠腺癌26(colon26)细胞株皮下接种于BALB/c小鼠,构建CC模型。将68只BALB/c小鼠随机分成5组:健康对照组、恶病质+等渗盐水对照组、恶病质+IN 0.5mg/(kg·d)组、恶病质+IN 1.0mg/(kg·d)组、恶病质+IN 2.0mg/(kg·d)组。监测各组小鼠一般情况、去瘤体重、血清IL-6、TNF-α的水平、各生化指标浓度变化、肿瘤组织中bcl-2的表达及癌细胞的凋亡和增殖等情况。结果恶病质小鼠去瘤体重明显下降(P<0.05),血清各生化指标不同程度的出现代谢消耗状态(P<0.05),血清IL-6,TNF-α水平明显升高(P<0.05),小鼠生存时间明显缩短(P<0.05)。IN中低剂量组尤其中剂量组IL-6、TNF-α水平显著降低(P<0.05),各生化指标亦有不同程度的改善(P<0.05),但IN高剂量组较对照组指标比较无统计学意义(P>0.05)。结论炎性细胞因子IL-6、TNF-α与CC的发生密切相关,适当剂量吲哚美辛有显著的逆转CC作用。

Objective To investigate the relationship between cytokine interleukin -6 （IL -6）, tumor necrosis factor-α （TNF -α） and experimental cancer cachexia as well as to observe the effect of indomethacin （IN） on the cachecitic mice. Methods Mice bearing colonic adenocarcinoma cells （colon26） were served as a model of cancer cachexia. Totally 68 healthy BALB/c mice were randomized into 5 groups： healthy control group （HC）, cancer cachexia with normal saline group （CC）, cancer cachexia with IN （0.5mg·kg^-1 · d^-1） group （IN1）, cancer cachexia with IN （1.0mg · kg^-1 · d^-1） group （IN2）, and cancer cachexia with IN （2.0mg · kg^-1 · d^-1 ） group （ IN3 ）. Physiological conditions and bodyweight were documented. Biochemical indicators, serum IL - 6, and TNF - α levels were evaluated. The expression of bcl - 2 gene and the distribution of cancer cell cycle in the tumor tissues were also analyzed by flow cytometry （FLM）. Results Tumor-bearing caused a wasting of non-tumor body weight degradation rate （P 〈 0. 05）. Serum IL-6 and TNF-α levels were significantly elevated accompanied with nutrition depletion （P 〈 0.05）. The life span of CC group was sigificantly shorter than HC group （ P 〈 0. 05）. The middle-and low-dose IN improved some biochemical indicators, reduced the concentration of IL-6 and TNF-α levels （P 〈 0.05）, down-regulated the cancer cell cycle compared with CC group; however, IN3 group had no significant statistical difference in these indicators （P 〈 0.05）. Conclusion Cell cytokine IL -6 and TNF -α are possibly associated with cancer cachexia. IN may potentially improve the condition of cancer cachexia by down-regulating cytokines levels, promoting apoptosis, and inhibiting the proliferation of cancer cell.