| 活性氧簇诱导硬皮病小鼠模型时效性的基础研究 |
| 投稿时间：2015-11-07 修订日期：2015-11-16 点此下载全文 |
| 引用本文：戴才俊,夏晓茹,吴佩亮,傅扬扬,黄晓颖,王良兴.活性氧簇诱导硬皮病小鼠模型时效性的基础研究[J].医学研究杂志,2016,45(4):80-84 |
| DOI：
10.11969/j.issn.1673-548X.2016.04.022 |
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| 基金项目:温州市科技局科技计划项目(Y20140250) |
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| 中文摘要:目的 应用活性氧簇(ROS)成分次氯酸(HClO)构建硬皮病小鼠动物模型,观察其皮肤纤维化和肺间质病变发生的时效特点。方法 36只6周龄雌性Balb/c小鼠随机平均分至造模组和对照组。造模组随机分3组,每组6只,分别予小鼠背部中央区皮肤皮下注射HClO 300μl,每日1次,分别持续4、5和6周;对照组随机分3组,每组6只,注射等量PBS,1次/日,分别持续4、5和6周。注射时间结束2周后处死小鼠,取注射部位周围、腹部皮肤及小鼠肺组织进行HE染色和Masson染色,镜下观察和测定各组皮肤厚度、胶原纤维含量,新鲜皮肤组织测定羟脯氨酸含量。结果 3组对照组(4、5、6周)小鼠背部和腹部皮肤均未出现表真皮层增厚和弹性降低,3组间皮肤厚度比较,差异无统计学意义(P>0.05);与对照组相比,连续注射4周HClO的造模组小鼠背部均出现弥漫增厚,弹性降低,真皮层明显增厚,腹部皮肤真皮层有所增厚;连续注射6周HClO的小鼠皮肤厚度较4周显著增加(P<0.05),胶原纤维增粗更加明显,并伴有纤维断裂,真皮层炎性细胞浸润,真皮血管壁增厚甚至闭塞。与对照组相比,连续注射4周的造模组小鼠未见明显肺间质病变,而6周造模肺组织出现肺泡间隔增厚,其间成纤维细胞增生,小血管壁增厚等纤维化表现。3组对照组(4、5、6周)小鼠之间背部皮肤的Masson染色胶原纤维组织化学指数比较,差异无统计学意义(P>0.05);与对照组相比,造模组背部皮肤的Masson染色胶原纤维组织化学指数升高,(P<0.05),且6周造模组的表达水平高于4周造模组,(P<0.05)。3组对照组(4、5、6周)小鼠之间背部皮肤的羟脯氨酸含量比较,差异无统计学意义(P>0.05);与对照组相比,造模组背部皮肤的羟脯氨酸含量升高(P<0.05),且6周造模组的表达水平高于4周造模组,(P<0.05)。结论 ROS构建的硬皮病小鼠动物模型随诱导时间的延长可出现注射区域外皮肤弥漫纤维化和硬皮病肺间质病变,该模型更加符合硬皮病皮肤和肺部病理改变特点。 |
| 中文关键词:硬皮病 动物模型 纤维化 活性氧簇 |
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| Basic Research of Timeliness on Reactive Oxygen Species Induced Scleroderma Mouse Model |
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| Abstract:Objective To establish a mouse model of scleroderma by local injections of ROS-HClO, then observe the timeliness characteristics of the progress of skin fibrosis and interstitial lung disease. Methods Thirty six Balb/c female mice were averagely divided into model and control groups randomly. Then model mice were divided into three groups randomly(6 in each group). 300μl HClO was daily injected subcutaneously into backs of model mice for 4, 5, and 6 weeks respectively. Control mice were divided into three groups randomly (6 in each group). Totally 300μl PBS was daily injected subcutaneously into backs of control group mice for 4, 5, and 6 weeks respectively. Two weeks after the end of injections, the mice were killed, the skin and lung samples were obtained for HE and Masson staining; the thickness of the skin was determined, the contents of collagen under masson staining and the contents of hydroxyproline of local injected skin were measured. Results In control groups of 4, 5 and 6 weeks, back and abdominal skin of all these groups didn't appear diffusely thickened, indicating the thickness of skin had no significant difference (P>0.05).Compared with control groups, back skin of model group in 4 weeks appeared diffusely thickened, elasticity was decreased, and dermis was obviously thickened; the thickness of skin increased more obviously in 6 weeks compared with model group of 4 weeks (P<0.05).Even more, collagen fibers markedly thickened and even cracked, inflammatory cells infiltrated in dermis layers, and vascular wall of dermis thickened and even occluded.The model group of 4 weeks had no noticeable change in lung tissues, while the model group of 6 weeks showed interstitial fibrosis in lung tissues. Changes included thickening in alveolar septum, fibroblasts proliferation in septum, thicker walls of small blood vessels. The collagen histochemical index of Masson staining in back skin of control groups of 4, 5 and 6 weeks had no significant difference (P>0.05). The collagen histochemical index of Masson staining in back skin of model groups were significantly different compared with control groups (P<0.05), and the index of model group in 6 weeks were much higher comparing with 4 weeks group (P<0.05). The contents of the hydroxyproline in back skin of control groups of 4, 5 and 6 weeks had no significant difference (P>0.05). The contents of the hydroxyproline in back skin of model groups were significantly different comparing with control groups (P<0.05), and the contents of model group in 6 weeks were much higher comparing with 4 weeks group (P<0.05). Conclusion The mice model of scleroderma induced by ROS can present diffused skin fibrosis and interstitial lung disease along with increased time. This animal model matches the characteristics and requirements of the pathological changes in the skin and lung of scleroderma. |
| keywords:Scleroderma Animal model Fibrosis Reactive oxygen species(ROS) |
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