消退素D1对荷结肠癌裸鼠体重、血液炎症细胞因子水平的影响及其对肿瘤的作用

The effect of Reslovin D1 on the body weight, the level of inflammatory cytokines and the tumor of nude mice with colon cancer

目的探讨消退素D1(RvD1)对荷结肠癌裸鼠体重、血液主要炎性因子水平的影响及其对肿瘤的作用。方法将6~8周龄体重18~20g的裸小鼠分为RvD1+肿瘤接种组、生理盐水+肿瘤接种组、空白对照组(n=6)。SW480结肠癌细胞接种后1周进行RvD1及生理盐水尾静脉注射,1w后采血并切取全部肿瘤组织,检测血液内的炎症细胞因子水平,检测肿瘤的大小、总重量及肿瘤内凋亡、坏死和活性细胞的比率。每2d记录大鼠的体重。结果实验周期内动物的体重分别为:空白对照组(26.9±4.2)g,生理盐水组(22.7±2.6)g,RvD1干预组(22.7±2.1)g。与空白对照组比较,接种肿瘤的两组在皮下种植肿瘤后6~7d小鼠体重开始下降,至实验终点时最明显。与生理盐水组比较,RvD1干预后的小鼠体重下降趋势得到改善,在9~14d期间最为明显。与空白对照组比较,生理盐水组炎症细胞因子水平明显升高,而RvD1干预1w后,炎症细胞因子水平明显下降,除白细胞介素(IL)-10外差异均有统计学意义。接种肿瘤的裸鼠均在皮下形成实体瘤,肿瘤大小(14.3±1.2)mm,平均肿瘤重量(0.24±0.03)g;使用RvD1干预后,肿瘤体积缩小为(9.4±0.9)mm,重量明显减轻为(0.17±0.02)g,两者差异有统计学意义(P=0.001)。生理盐水组和RvD1干预组的肿瘤组织内凋亡细胞的比例分别为(18.9±3.4)%比(45.3±4.9%),坏死细胞的比例分别为(29.7±7.5)%比(17.1±1.4%),活性细胞比例为(51.4±8.2)%比(37.6±5.3%)。比较生理盐水组,RvD1干预后肿瘤组织内,凋亡细胞的比例明显上升(P=0.001),坏死细胞比例明显下降(P=0.002),活性细胞比例明显下降(P=0.006)。结论与生理盐水比较,RvD1能通过抑制荷结肠癌裸鼠体内的炎症细胞因子水平,提高肿瘤组织内凋亡细胞,降低坏死细胞比例,使活性肿瘤细胞比例下降,减小平均肿瘤体积和重量,并使动物的体重下降趋势得到改善。

Objective To investigate the effect of Resolvin D1 (RvD1) on the body weight, the level of inflammatory cytokines and the tumor of nude mice with colon cancer. Methods 6-8-week-old and 18-20 weight nude mice were divided into RvD1+ tumor inoculation group, saline+ tumor inoculation group and blank control group (n=6). One week after inoculation of SW480 colon cancer cells, RvD1 and saline were injected into the tail vein. After 1 week, blood was collected and all tumor tissues were harvested. The levels of inflammatory cytokines in the blood were detected, and the size and total weight of the tumors and The ratio of apoptosis, necrosis and active cells in the tumor were detected. The body weight of the mice was recorded every 2 days. Results The body weights of the animals in the experimental period were: blank control group (26.9±4.2) g, saline group (22.7±2.6) g, and RvD1 intervention group (22.7±2.1) g. Compared with the blank control group, the weight of the mice in the two groups inoculated with tumors began to decrease 6-7 days after subcutaneous implantation of tumors, and was most obvious at the end of the experiment. Compared with the saline group, the weight loss trend of the mice after RvD1 intervention was improved, and it was most obvious during the 9-14 d period. Compared with the blank control group, the level of inflammatory cytokines in the saline group was significantly increased, and the level of inflammatory cytokines was significantly decreased after 1 w of RvD1 intervention, with statistical significance except interleukin (IL)-10. The nude mice inoculated with tumors formed solid tumors under the skin. The tumor size was (14.3±1.2) mm, and the average tumor weight was (0.24±0.03) g. After intervention with RvD1, the tumor volume was reduced, and the size was (9.4±0.9) mm. The weight was (0.17±0.02) g, and the weight were statistically significant, P=0.001. The ratio of apoptotic cells in the saline group and the RvD1 intervention group was (18.9±3.4)% vs. (45.3±4.9)%, and the proportion of necrotic cells was (29.7±7.5)% vs. (17.1±1.4)%, the ratio of active cells (51.4±8.2)% vs. (37.6±5.3)%. Compared with the saline group, the proportion of apoptotic cells in the tumor tissue increased significantly after RvD1 intervention (P=0.001), the proportion of necrotic cells decreased significantly (P=0.002), and the proportion of active cells decreased significantly (P=0.006). Conclusion Compared with saline, RvD1 inhibited the level of inflammatory cytokines in nude mice with colon cancer, increased apoptotic cells in tumor tissue, reduced the proportion of necrotic cells, decreased the proportion of tumor cells and reduced the average tumor volume and weight. Thus, the weight decline of the animal was improved.