氯膦酸二钠脂质体灌肠缓解葡聚糖硫酸钠诱导的结肠炎  

Liposomal Clodronate Enema Ameliorates Dextran Sulfate Sodium-Induced Murine Colitis

作　　者：杨永红 李海波[5] 王兴民 

机构地区：[1]甘肃博睿生物科技有限公司,甘肃兰州 [2]甘肃省儿童医院,甘肃兰州 [3]兰州大学第二医院,甘肃兰州 [4]甘肃省消化肿瘤重点实验室,甘肃兰州 [5]南通市妇幼保健院,江苏南通

出　　处：《世界肿瘤研究》2018年第1期26-35,共10页World Journal of Cancer Research

基　　金：兰州市人才创新创业项目(2014-RC-81);人社部2015年留学人员回国创业启动支持计划资助。

摘　　要：目的:证明一种新型氯膦酸二钠脂质体灌肠剂可清除小鼠肠道巨噬细胞从而缓解葡聚糖硫酸钠诱导的结肠炎。方法:用含葡聚糖硫酸钠的饮用水诱导野生型小鼠结肠炎,结肠炎小鼠每周用氯膦酸二钠脂质体和空脂质体灌肠一次,共灌肠十次。小鼠结肠组织用苏木精–伊红染色后判定炎症程度,用免疫组织化学染色法检测巨噬细胞的数目、环氧合酶2 (COX-2)以及增殖细胞核抗原(PCNA),并用酶联免疫吸附试验检测血清中的炎性细胞因子TNFα和IL-6。结果:免疫组织化学及H&E染色显示,与葡聚糖硫酸钠肠炎小鼠以及空脂质体灌肠的肠炎小鼠相比,氯膦酸二钠脂质体灌肠可有效地清除肠道组织巨噬细胞从而减轻了葡聚糖硫酸钠诱导的结肠炎。另外,用氯膦酸二钠脂质体灌肠剂清除巨噬细胞显著地降低了血清中炎性细胞因子TNFα和IL-6的产生以及肠道组织中COX-2和PCNA的表达。结论:该新型氯膦酸二钠脂质体灌肠剂可有效地清除肠道巨噬细胞从而减少炎性细胞因子和COX-2的表达、抑制肠道上皮细胞的增生和结肠炎,有望用于结肠炎的辅助治疗和结直肠癌的预防。Aim: To demonstrate that depletion of colon macrophages using a novel liposomal clodronate enema ameliorates dextran sulfate sodium (DSS)-induced colitis. Methods: Murine colitis was in-duced by DSS in drinking water and treated with liposomal clodronate enemas or sham liposomal enemas once a week for a total of 10 treatments. Inflammation was evaluated for colon biopsies following hematoxylin and eosin staining. Colon macrophages, cyclooxygenase-2 (COX-2), and proliferating cell nuclear antigen (PCNA) were determined by immunohistochemical staining. Se-rum TNFα and IL-6, two inflammatory cytokines, were analyzed by enzyme-linked immunosorbent assay. Results: Immunohistochemical staining showed that macrophages were efficiently depleted in colon biopsies from mice treated with liposomal clodronate enemas compared to sham liposomal enemas. In addition, colitis was remarkably ameliorated for mice treated with liposomal clodronate enemas compared to sham liposomal enemas or DSS alone. Finally, the production of TNFα, IL-6, COX-2, and PCNA significantly decreased by depleting colon macrophages using liposomal clodronate enemas compared to sham liposomal enemas or DSS alone. Conclusion: This liposomal clodronate enema is capable of depleting colon macrophages, reducing inflammatory cytokines and COX-2, blocking colon epithelial cell proliferation and colitis. It may be used as an adjuvant therapy for colitis and colorectal cancer prevention.

关 键 词：氯膦酸二钠 脂质体 巨噬细胞清除剂 细胞凋亡 DSS结肠炎 

分 类 号：R28[医药卫生—中药学]