重组人干扰素-β-1a对BALB/C小鼠硬化症的疗效评价  

Treatment of recombinant human interferon-β-1a on sclerosis of BALB/C mice

作　　者：张丽君[1] 张英[1] 陈献雄[1] 王妍[1] 张微微[2] 韦康[2] 田建明[2] 

机构地区：[1]深圳职业技术学院应用化学与生物技术学院,广东深圳518055 [2]吉林省中医药科学院,吉林长春130012

出　　处：《中国新药与临床杂志》2014年第9期677-682,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：广东省教育部产学研结合项目(2012B091100408);深圳市科技创新委资助项目(JAS2009032012-00A;GGJS201303311523444401)

摘　　要：目的研究本实验室表达的重组人干扰素-β-1a(IFN-β-1a)对BALB/C小鼠硬化症的疗效。方法通过皮下注射博来霉素制BALB/C小鼠硬化症模型,并设空白对照组,制模成功小鼠分为空白对照组,模型组,泼尼松龙组,进口重组人IFN-β-1a组和重组人IFN-β-1a低、中、高剂量组。上述各药物组分别皮下注射相应受试药物20次(隔日一次),空白对照组和模型组皮下注射生理盐水。取皮肤及心、肺、肾做病理组织学检查;采用碱水解法测定皮肤羟脯氨酸含量;采用免疫组化方法和RT-PCR技术检测小鼠造模处皮肤胶原蛋白-Ⅰ、胶原蛋白-Ⅲ、单核细胞趋化蛋白-1、α-平滑肌肌动蛋白、转化生长因子-β1、转化生长因子-β2表达。结果病理学检测结果显示,使用本实验室表达重组人IFN-β-1a注射液治疗后,皮下组织纤维化程度、肺纤维化程度明显改善,造模处皮肤羟脯氨酸的含量也有明显下降(P<0.05或P<0.01),且中、高剂量组与进口重组人IFN-β-1a效果无显著差异(P>0.05);免疫组化检测结果和RT-PCR技术检测结果均显示,重组人IFN-β-1a注射液中、高剂量组小鼠造模处皮肤上述各蛋白和mRNA的表达均显著低于模型组(P<0.05或P<0.01),且中、高剂量组与进口重组人IFN-β-1a组无显著差异(P>0.05)。结论本实验室表达的重组人IFN-β-1a可显著改善BALB/C小鼠硬化症的症状,与进口重组人IFN-β-1a效果相当。AIM To evaluate the effects of recombinant human interferon （IFN） -β-1a expressed in our laboratory on the sclerosis of BALB/C mice. METHODS The sclerosis model of BALB/C mice were induced by hypodermic injection of bleomycin. The multiple sclerosis model of BALB/C mice then were divided into control group, model group, prednisolone group, imported recombinant human IFN- β- 1a group and recombinant human IFN-β-1a low, middile and high dose groups expressed in our laboratory. The drug groups mentioned above were treated with drugs respectively in subcutaneous injection for 20 times, qod and the control group and model group were treated with saline in subcutaneous injection. The skins, lungs, hearts and kidneys of all groups were sampled for histopathology examination. The contents of hydroxyproline in the skin were detected by alkali hydrolysis method. The expression of collagen （COL） - I , COL-HI, monocyte chemotactic protein-1 （MCP- 1）, α-smooth muscle actin （α-SMA）, transforming growth factor （TGF） -β1, TGF-β2 were detected using immunohistochemical method and RT-PCR method. RESULTS The histopathology results showed that the fibrosis stage of subcutaneous and lung tissue improved obviously and the contents of hydroxyproline were also decreased significantly after treatment with recombinant human IFN- β- 1a expressed in our laboratory （P 〈 0.05 or P 〈 0.01）. Moreover, there was no significant difference between middle, high dose groups and imported recombinant human IFN-β-1a respectively （P 〉 0.05）. The protein and mRNA expressions of COL- I , COL- Ⅲ, MCP-1, a-SMA, TGF-β1 and TGF-β2 reduced significantly after treatment by the middle, high dose groups of recombinant human IFN- β- 1a expressed in our laboratory （P 〈 0.05 or P 〈 0.01 ） and there also was no significant difference between middle, high dose groups and imported recombinant human IFN- β- 1a respectively （P 〉 0.05）. CONCLUSION The recombinant human IFN- β - 1a expressed in our laboratory

关 键 词：干扰素Β 多发性硬化 纤维相关胶原类 博来霉素 

分 类 号：R963[医药卫生—微生物与生化药学] R986[医药卫生—药理学]