白细胞介素11防治大鼠大剂量甲氨蝶呤致黏膜炎的实验研究  

The effects of interleukin-11 on high dose methotrexate(HDMTX) induced mucositis in Wistar rats

作　　者：韩月芹[1] 陈力军[1] 孙晓静[2] 赵国法[2] 程秀英[1] 

机构地区：[1]山东大学临床学院山东省立医院,济南山东聊城市人民医院儿科252000 [2]山东聊城市人民医院

出　　处：《中华血液学杂志》2004年第12期740-744,共5页Chinese Journal of Hematology

摘　　要：目的　观察白细胞介素 11(IL 11)防治大剂量甲氨蝶呤 (HDMTX)致Wistar大鼠小肠黏膜炎的疗效及IL 11对HDMTX抑制人T淋巴细胞白血病细胞系CEM增殖作用的影响。方法　Wistar大鼠腹腔注射MTX 1ml(10 0mg/kg) ,同时皮下注射IL 114 75 μg·kg-1·d-1(大剂量 )或 15 0 μg·kg-1·d-1(小剂量 ) ,分 2次 ,共 2d ;同时设生理盐水对照组及单独注射MTX对照组。各组大鼠于MTX注射后第1,3,5 ,7天处死 ,观察各组大鼠死亡率、小肠组织形态学及超微结构变化以及小肠隐窝细胞增殖细胞核抗原 (PCNA)变化情况。MTT法观察不同浓度IL 11对CEM细胞增殖的影响及对HDMTX抑制作用的影响。结果　在体内 ,IL 11可明显降低小肠组织病理学积分 ,增加小肠绒毛的高度 ,增加绒毛高度/隐窝深度的比值 ,促进小肠隐窝细胞核的增殖 ,使实验鼠死亡率下降。IL 11预防治疗组效果最好 ,与MTX对照组比较 ,差异有统计学意义 (P <0 .0 1)。在体外 ,IL 11对CEM细胞的增殖及HDMTX的抑瘤作用无明显影响。结论IL 11可以明显减轻HDMTX诱发的小肠黏膜炎的严重程度 ,缩短病程 ,提高实验动物的存活率 ,IL 11可以安全地用于儿童急性淋巴细胞白血病HDMTX的化疗。Objective To explore the therapeutic effect of interleukin 11(IL 11)on high dose methotrexate(HDMTX)induced mucositis in Wistar’s rats, the proliferative effect on CEM leukemia cell line and the antitumor effect on HDMTX. MethodsNinety five 5 week old,120 150 grams weight Wistar rats were randomly divided into five groups. Group A is normal control (n=15), group B MTX control(n=20), group C IL 11 pretreatment group before MTX injection(n=20), group D(n=20) the high dose IL 11 group (475 μg·kg -1 ·d -1 ) after MTX injection, group E(n=20) the low dose IL 11 group (150 μg·kg -1 ·d -1 ) after MTX injection. All rats in group B ～ E were given 1 ml MTX intraperitonealy(100 mg/kg). Rats were killed at day 1,3,5,7after MTX injection. The mortality rates, changes of small intestine tissue morphology and ultra structure were observed. The proliferation of small intestine crypt cell was assayed by proliferating cell nuclear antigen(PCNA) immunohistochemical staining. MTT method was used to detect the proliferation of CEM cell line.Result IL 11 treatment resulted in a significant increase of survival of HDMTX treated rats, increased of small intestinal villus length and villus/crypt ratio. IL 11 administration was associated with enhancement of small intestine mucosa recovery after HDMTX therapy. Group C showed a greater effect than group B (P<0.01). IL 11 had no effect on CEM cell proliferation. ConclusionIL 11 has a significant mitigating effect on high dose MTX induced intestinal mucositis in rat, and significantly increase the survival of the rats. IL 11 could be safely used in the HDMTX treatment of childhood acute lymphocyte leukemia.

关 键 词：IL—1 MTX 大剂量 大鼠 甲氨蝶呤 白细胞介素11 小肠 细胞核 白血病细胞系 实验鼠 

分 类 号：R733.7[医药卫生—肿瘤]