粒-巨噬细胞集落刺激因子促进草酸铂腹腔化疗下大鼠结肠吻合口愈合机制的初步研究  

PRELIMINARY STUDY ON MECHANISMS OF GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR IN ENHANCING IMPAIRED COLONIC ANASTOMOTIC HEALING IN RATS TREATED WITH INTRAPERITONEAL OXALIPLATIN

作　　者：刘勇[1] 杨阳[2] 刘辉[3] 宋云骏 贾喜花[1] 张晓伟[1] 郭建美[1] 

机构地区：[1]保定市第一中心医院肿瘤内科,河北保定071000 [2]河北大学中医学院 [3]中国医学科学院北京协和医学院基础医学研究所 [4]承德市肿瘤医院肿瘤外科

出　　处：《中国修复重建外科杂志》2012年第10期1232-1236,共5页Chinese Journal of Reparative and Reconstructive Surgery

摘　　要：目的观察粒-巨噬细胞集落刺激因子(granulocyte macrophage-colony stimulating factor,GM-CSF)局部应用于草酸铂腹腔化疗下大鼠结肠吻合口愈合过程中的组织学变化,探讨其作用机制。方法 10周龄清洁级雄性Wistar大鼠60只,体重(235±18)g,制备结肠吻合模型,随机分为3组(n=20)。术后1 d,A、B组腹腔对应注射10 mL 5%葡萄糖溶液、10 mL含草酸铂(25 mg/kg)的5%葡萄糖溶液;C组术后即刻吻合口区域注射50μg GM-CSF,术后1 d腹腔注射10 mL含草酸铂(25 mg/kg)的5%葡萄糖溶液。术后观察大鼠一般情况,于2、3、5、7 d测量吻合口破裂压,组织学观察并计算吻合口愈合指数,免疫组织化学染色检测Ⅰ型胶原纤维阳性染色面积。结果术后各组大鼠均存活至实验完成。术后2、3 d各组吻合口破裂压相似(P>0.05);5、7 d时,B组吻合口破裂压显著低于A、C组(P<0.05),A、C组间差异无统计学意义(P>0.05)。吻合口愈合指数结果示,术后各时间点,A、C组间单核细胞浸润、黏膜上皮细胞覆盖、黏膜下层-肌层衔接程度及肉芽组织形成相似(P>0.05),A、C组黏膜上皮细胞覆盖及肉芽组织形成均显著优于B组(P<0.05);术后2、3 d,A、C组单核细胞浸润显著优于B组(P<0.05),5、7 d黏膜下层-肌层衔接程度优于B组(P<0.05)。术后2、3 d,各组Ⅰ型胶原纤维阳性染色面积比较差异均无统计学意义(P>0.05);5、7 d时A、C组Ⅰ型胶原纤维阳性染色面积显著高于B组(P<0.05),A、C组间比较差异无统计学意义(P>0.05)。结论局部注射GM-CSF可通过早期动员巨噬细胞浸润,提高大鼠黏膜下层胶原纤维沉积,从而加速结肠愈合进程。Objective To investigate the mechanisms of local flapplication of granulocyte macrophagecolony stimulating factor（GM-CSF） on healing of colonic anastomoses impaired by intrflaperitoneal oxaliplatin in rats.Methods Sixty 10-week-old male Wistar rats were made the colonic anastomosis model and randomized into 3 groups,20 rats in each.The rats received intrflaperitoneal injection of 5% dextrose in group A,and intrflaperitoneal injection of 5% dextrose and 10 mL oxaliplatin（25 mg/kg） in group B at 1 day;and 50 μg GM-CSF was injected into the perianastomotic area immediately after operation and 10 mL intrflaperitoneal oxaliplatin（25 mg/kg） was given at 1 day.The general situation of rats was observed after operation.Anastomotic healing was tested by measuring the bursting pressure in vivo at 2,3,5,7 days.Anastomotic healing score was evaluated by histological staining.Immunohistochemical staining of the anastomotic site was used to determine the amount of collagen type I content.Results All animals survived to the experiment end.There was no significant difference in the bursting pressure among 3 groups at 2 and 3 days（P 0.05）;the bursting pressure of group B was significantly lower than that of groups A and C（P 0.05）.There was no significant difference in mononuclear cells in ltration,mucosal epithelialization,submucosa-muscle layer connection degree,and granulation tissue formation between groups A and C at di erent time points（P 0.05）;groups A and C were significantly better than group B in mucosal epithelialization and granulation tissue formation（P 0.05）.Groups A and C were significantly better than group B in mononuclear cells in ltration at 2 and 3 days,and in submucosa-muscle layer connection degree at 5 and 7 days（P 0.05）.There was no significant difference in collagen type I content among 3 groups at 2 and 3 days（P 0.05）;the content of collagen type I in groups A and C were significantly higher than that in group B（P 0.05） at 5 and 7 days.Conclusion Local administrati

关 键 词：粒-巨噬细胞集落刺激因子 结肠吻合口 草酸铂 愈合机制 大鼠 

分 类 号：R73-36[医药卫生—肿瘤]