Objective: To investigate the mechanism of electroacupuncture (EA) "Zusanli" (ST36) in delaying colon "inflammation-cancer transformation" in mice by anti-inflammatory.
Methods: C57BL/6J mice were randomly divided into normal, model and EA groups, with 12 mice in each group. The mouse model of colorectal cancer (CRC) was established by intrape-ritoneal injection of azomethane (AOM) and feeding dextran sodium sulfate (DSS). At the beginning of the 2nd cycle, EA was applied to bilateral ST36 for 30 min once every other day for 12 times. The number of colon tumors in each group was observed, and the weight and length of colon were recorded. The contents of interleukin (IL)-1β, IL-6, IL-17A, IL-23, tumor necrosis factor (TNF)-α and CXC chemokine ligand 1 (CXCL1) of serum and colon tissue were detected by MSD multifactorial assay.The apoptosis of local cells in colon tumor was observed by TUNEL staining. Cell proliferation in colon tumor was observed by immunohistochemistry.
Results: Compared with the normal group, the colon length was significantly shortened (P<0.05) and the colon mass was significantly increased (P<0.001) in the model group, the contents of IL-1β, IL-6, TNF-α, IL-17A and CXCL1 of serum and colon tissue were significantly increased (P<0.05, P<0.01, P<0.001), and the content of IL-23 was increased in colon tissue (P<0.05) in the model group. Compared with the model group, the colon mass was decreased (P<0.05) and the contents of IL-1β, IL-6, TNF-α and IL-17A in serum were decreased (P<0.05), while the contents of IL-17A, CXCL1 and IL-23 in colon tissue were decreased (P<0.05) in the EA group, the percentage of local apoptotic cells in the EA group was increased (P<0.001), the percentage of PCNA positive cells was decreased (P<0.001), the number of tumors and the tumor volume were significantly decreased (P<0.01, P<0.05). The contents of IL-6, TNF-α, IL-17A and IL-23 in serum of CRC mice were positively correlated with tumor burden (P<0.05).The contents of IL-1β, TNF-α, CXCL1 and IL-23 in colon tissue of CRC mice were positively correlated with tumor burden (P<0.05).
Conclusion: Electroacupuncture at ST36 can inhibit the inflammatory response of AOM/DSS inflammatory associated CRC mice and delay the "inflammation-cancer transformation" of colon.
目的:探讨电针“足三里”通过抗炎延缓小鼠结肠“炎-癌转化”的机制。方法:C57BL/6J小鼠随机分为正常组、模型组和电针组, 每组12只。采用腹腔注射偶氮甲烷(AOM)联合饲喂葡聚糖硫酸钠(DSS)制备小鼠结直肠癌(CRC)模型, 在开始饲喂第2个循环的DSS当天对电针组小鼠双侧“足三里”行电针治疗, 每次30 min, 隔日1次, 共12次。观察各组小鼠结肠肿瘤数量并测量结肠质量和长度;采用MSD多因子检测技术检测各组小鼠血清和结肠组织白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、CXC趋化因子配体1(CXCL1)、IL-17A和IL-23含量;采用TUNEL染色法观察结肠肿瘤局部细胞凋亡情况;采用免疫组织化学法观察结肠肿瘤局部细胞增殖情况。结果:与正常组比较, 模型组小鼠结肠长度明显缩短(P<0.05), 结肠质量明显增加(P<0.001);血清和结肠组织IL-1β、IL-6、TNF-α、IL-17A、CXCL1含量升高(P<0.05, P<0.01, P<0.001), 结肠组织IL-23含量明显升高(P<0.05)。与模型组比较, 电针组小鼠结肠质量降低(P<0.05), 血清中IL-1β、IL-6、TNF-α、IL-17A含量降低(P<0.05), 结肠组织中IL-17A、CXCL1和IL-23含量降低(P<0.05), 结肠肿瘤局部凋亡细胞百分比增加(P<0.001), 增殖细胞核抗原(PCNA)阳性细胞百分比显著减少(P<0.001), 结肠肿瘤数量明显减少(P<0.01), 肿瘤平均体积缩小(P<0.05)。CRC小鼠血清中IL-6、TNF-α、IL-17A和IL-23含量与肿瘤负荷呈正相关(P<0.05);CRC小鼠结肠组织中IL-1β、TNF-α、CXCL1和IL-23含量与肿瘤负荷呈正相关(P<0.05)。结论:电针“足三里”可抑制AOM/DSS炎性相关性CRC小鼠的炎性反应, 延缓结肠“炎-癌转化”。.
Keywords: Colorectal cancer; Electroacupuncture; Inflammatory reaction; Inflammatory-cancer transformation.