羧甲基茯苓多糖对氟尿嘧啶致肠炎小鼠的保护作用  

Protective effects of CMP on 5-Fu-induced intestinal mucositis of mice

作　　者：王灿红 何晓山[2] 张丽静[1] 霍小位 刘冬羽[1] 韩嘉媛[1] 李立勇[1] 曹丽[1] 

机构地区：[1]中国医学科学院药用植物研究所,北京100193 [2]云南中医学院中药学院,云南昆明650500

出　　处：《中国药理学通报》2016年第4期484-489,共6页Chinese Pharmacological Bulletin

基　　金：国家科技部"重大新药创制"科技重大专项课题-早期成药性评价关键技术(No2012ZX09501001-004);国家科技部"重大新药创制"科技重大专项-综合性新药研究开发技术大平台-创新药物研究开发技术平台建设(No2012ZX09301-002-001-026)

摘　　要：目的探讨羧甲基茯苓多糖(carboxymethylpachymaran,CMP)对氟尿嘧啶(fluorouracil,5-Fu)所致小鼠肠黏膜炎的改善、肠道保护作用及可能作用机制。方法建立5-Fu小鼠肠黏膜炎模型,随机分组、给药。炭末推进法测定小鼠肠推进率,并测量小鼠结肠长度;生物化学方法检测派氏集合淋巴结(PPs)匀浆上清液中活性氧类(ROS)和谷胱甘肽(GSH)的含量、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的活力;ELISA法检测PPs匀浆上清中IL-1β的含量;小鼠结肠做病理组织切片观察,免疫组化法检测结肠组织中NF-κB和p-p38的表达。结果与5-Fu模型组比较,CMP能明显延长5-Fu所致的结肠缩短(P<0.01);明显促进肠推进功能(P<0.05);结肠病理学切片显示,CMP能明显减轻5-Fu所致的结肠黏膜上皮杯状细胞丢失、隐窝深度变浅及炎症细胞浸润;并且明显升高PPs匀浆上清中GSH含量、CAT和GSH-Px的活性(P<0.01或P<0.05),降低ROS(P<0.05)和IL-1β的含量(P<0.01);免疫组化结果显示,相比5-Fu组,CMP明显降低结肠组织NF-κB和p-p38的表达。结论 CMP能够减轻5-Fu所致小鼠结肠黏膜炎,改善5-Fu所致的肠道传输功能失调,并保护5-Fu对肠道的氧化损伤和细胞凋亡,其机制可能与增强机体抗氧化、抑制炎症及抗凋亡作用有关。Aim To evaluate the mucosal-protective effects of carboxymethylpachyman( CMP) on Fluorouracil( 5-Fu)-induced mice intestinal mucositis and explore its mechanisms. Methods ICR mice were assigned randomly to four groups: normal group( n = 8; receiving pure water orally for 14 d),CMP group( n = 8;200 mg·kg^(-1) CMP for 14 d orally),5-Fu group( n =8; 25 mg·kg^(-1) 5-Fu for 7 d,intraperitoneally( i. p.),and CMP + 5-Fu group( n = 8; 200 mg·kg^(-1) CMP for 14 d orally and 25 mg·kg^(-1) 5-Fu for 7 d,i. p.). At day 14 the mice were sacrificed. The intestinal propelling rate and the colon length were measured. ROS,GSH and IL^(-1) βcontents,and CAT,GSH-Px activities in homogenate supernatant of PPs were measured by kits for observing the effects of CMP on mice lipid peroxidation and intestinal mucosal inflammatory induced by 5-Fu. Colon tissues were used for hematoxylin and eosin( HE) staining for the determination of the effect of CMP on mice colon histopathology,immunohistochemistry for the protein levels of NF-κB and p-p38. Results CMP significantly extended colon lengths,accelerate the intestinal propelling rates,reduced colonic mucosa epithelium goblet cell loss,inflammatory cells infiltration,and crypt depth shallow induced by 5-Fu. CMP obviously reduced ROS and IL-1β contents,and prevented reductions in homogenate supernatant of PPs GSH content,CATand GSH-Px activities by 5-Fu administration,and also reduced the expression of NF-κB and p-p38 in colon tissues. However,CMP alone had no effect on the colon of normal mice. Conclusion The current study demonstrates that CMP may have significant protective effects against 5-Fu-induced intestinal mucositis. Its mechanism may be related to enhancing the antioxidant activity,anti-inflammatory and anti-apoptotic effects.

关 键 词：羧甲基茯苓多糖 抗氧化 氟尿嘧啶 肠黏膜炎 肠推进 肠道保护 

分 类 号：R-332[医药卫生] R284.1