FOXO3调控NF-κBp50表达介导肠上皮细胞凋亡参与溃疡性结肠炎相关癌变及健脾清热活血方药干预研究  

Explore the intervention mechanism of Jian Pi Qing Re Huo Xue decoction by detecting Foxo3 mediated nuclear factor-ΚBp50 influencing enterocyte apoptosis in ulcerative colitis associated carcinogenesis

作　　者：王其进 陈玉[2] 张涛[2] 平倩[2] 王小平[3] 

机构地区：[1]海南省中医医院,海南海口570100 [2]广西中医药大学附属瑞康医院,广西南宁530011 [3]江西中医药高等专科学校,江西抚州344700

出　　处：《时珍国医国药》2015年第12期3043-3046,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(No.81260536);广西自然科学基金(No.2013GNSFAA019116)

摘　　要：目的观察溃疡性结肠炎相关癌变(ulcerative colitis associated carcinogenesis,UCAC)结肠黏膜FOXO3、NF-κBp50、C-myc、肠上皮细胞凋亡及健脾清热活血方药对上述指标的影响,探讨健脾清热活血方药防治UCAC的可能机制。方法120只SPF级雄性Balb-c按体质量随机分为正常组、模型组、对照组(美沙拉嗪组)、治疗组(低、中、高剂量组),采用DMH/DSS复合法制备UCAC模型,除正常组同步饲养外,其余各组分别予不同药物干预20周,第20周末处死全部动物。采用TUNEL染色检测肠上皮细胞凋亡;采用Real-time PCR及Western-bloting技术检测FOXO3、NF-κBp50、C-myc表达变化。结果 UCAC模型组小鼠结肠黏膜上皮细胞凋亡率为(18.65±2.47)%,结肠Foxo3、NF-ΚBp50、C-myc基因及其蛋白表达上升,该变化与UCAC组织病理学积分呈正相关;治疗组结肠黏膜上皮细胞凋亡率为(6.54±1.13)%,结肠FOXO3、NF-κBp50、C-myc基因及其蛋白表达较模型组比较明显下降,有统计学意义(P<0.05)。结论 FOXO3上调NF-κBp50表达诱导肠上皮细胞凋亡加速,破坏肠黏膜屏障,导致炎症持续在UCAC发病中占据重要地位;健脾清热活血方药可能通过下调FOXO3、NF-κBp50、C-myc表达,介导肠上皮细胞凋亡,修复肠黏膜屏障而发挥缓解UCAC的效用。Objective We aim to discuss the mechanism of Jian Pi Qing Re Huo Xue decoction in preventing the onset of UCAC by observing changes of Foxo3,NF-κBp50,and C-myc in colon mucosa and the intestinal epithelial cell apoptosis.Methods 120 SPF Balb / c rats were randomly divided into normal group,blank group,control group（ mesalazine group） and treatment groups（ low,medium and high dose group） according to weight. The UCAC model was prepared by DMH / DSS commixture. Except normal group,the other groups were given the intervention of different drugs for 20 weeks. All the rats were killed at the end of 20 th week. The apoptosis rates of intestinal epithelial cells were detected by TUNEL staining. The expressions of Foxo3,NF-κBp50,and C-myc were detected by the Real-time PCR and Western-blotting. Results The apoptosis rate of intestinal mucosal epithelial cells in the UCAC group was 18. 65% ± 2. 47%. The expressions of colon Foxo3,NF-κBp50,and C-myc were on the increment. These changes were positively correlated with UCAC pathological integral calculus. The apoptosis rate of intestinal mucosal epithelial cell in treatment group was 6. 54% ± 1. 13%. And the expressions of colon Foxo3,NF-κBp50,and C-myc were much lower than blank group. There was a statistical significant different（ P〈0. 05）. Conclusion The rising expression of NF-κBp50 which led to the accelerated apoptosis of intestinal epithelial cell was regulated by Foxo3. The damage of intestinal mucosa barrier and persistent inflammation play an important role in the pathogenesis of UCAC. Jian Pi Qing Re Huo Xue decoction exerts a distinct effect on relieving symptoms of UCAC by down-regulating the expression of colon Foxo3,NF-κBp50,and C-myc.

关 键 词：FOXO3 核转录因子-κBp50 肠上皮细胞凋亡 溃疡性结肠炎相关癌变 健脾清热活血方药 

分 类 号：R285.5[医药卫生—中药学]