不同浓度博来霉素诱导硬皮病小鼠模型胃肠道并发症的病理研究

Pathological study of gastrointestinal complications in scleroderma model mice induced by different concentrations of Bleomycin

目的探讨不同浓度博来霉素(BLM)诱导硬皮病小鼠模型胃肠道并发症的病理研究。方法选取雌性BALB/c小鼠18只,采用随机数字法将其分为空白对照组、模型1组和模型2组,各6只。空白对照组背部皮下注射0.1 ml磷酸缓冲液;模型1组注射0.1 ml 200μg/ml BLM;模型2组注射0.1 ml 500μg/ml BLM。三组均连续皮下注射28 d,1次/d。于第28天处死小鼠,观察比较三组小鼠背部注射区皮肤、食管、小肠组织切片的病理学特征,测定其血清D-乳酸(D-LA)和二胺氧化酶(DAO)水平。结果模型1组和模型2组真皮厚度均厚于空白对照组(P<0.05),模型2组真皮厚度厚于模型1组(P<0.05)。模型1组和模型2组食管、小肠胶原容积评分均高于空白对照组(P<0.05),模型2组食管、小肠胶原容积分数均高于模型1组(P<0.05)。模型1组和模型2组血清D-LA和DAO水平均高于空白对照组(P<0.05);模型2组血清D-LA和DAO水平均高于模型1组(P<0.05)。结论两种造模方法都能出现皮肤和肠道炎症浸润及纤维化改变,500μg/ml BLM诱导的硬皮病小鼠模型具有更明显皮肤和肠道病理改变。

Objective To investigate the pathological study of gastrointestinal complications induced by different concentrations of Bleomycin(BLM)in scleroderma model mice.Methods A total of 18 female BALB/c mice were divided into control group,model group 1,and model group 2 by random number table method,with six mice in each group.The control group were injected with 0.1 ml phosphate buffered saline subcutaneously on the back;the model group 1 were injected 0.1 ml 200μg/ml BLM;the model group 2 were injected 0.1 ml 500μg/ml BLM.Three groups were continuously injected for 28 days,once per day.On the 28th day,the mice were sacrificed,and the pathological features of the skin in the injected area,the esophagus,and the small intestinal tissue were observed.The serum levels of D-lactic acid(D-LA)and diamine oxidase(DAO)were gavaged.Results The dermis thickness in model group 1 and model group 2 were thicker than those in the control group(P<0.05),and the dermis thickness of model group 2 was thicker than that in model group 1(P<0.05).The collagen volume scores of the esophageal and small intestinal in model group 1 and model group 2 were higher than those in the control group(P<0.05),and the esophageal collagen volume scores in model group 2 were higher than those in model group 1(P<0.05).The serum levels of D-LA and DAO in model group 1 and model group 2 were higher than those in the control group(P<0.05),while the serum levels of D-LA and DAO in model group 2 were higher than those in model group 1(P<0.05).Conclusion Both modeling methods can show inflammatory infiltration and fibrotic changes in skin and intestine,and the 500μg/ml BLM-induced scleroderma model has more obvious changes in skin and intestinal pathological.