IL-17单克隆抗体对肺纤维化大鼠的保护作用及部分机制研究

发布时间：2018-10-14 18:12

【摘要】：目的探讨白介素(IL)-17单克隆抗体(m Ab)对博莱霉素所致大鼠肺纤维化的保护作用及相关机制。方法将♂SD大鼠75只随机分为正常对照组、假手术组、模型组、非特异性Ig G组、IL-17 m Ab组,各组15只,后3组大鼠予以博莱霉素A5气管内注入构建肺纤维化模型,而假手术组给予等量生理盐水气管内注入。后2组于d 7、14、21分别给予非特异性IgG、IL-17 mAb尾静脉注射,其余3组给予等量生理盐水尾静脉注射。所有大鼠d 28处死,留取肺组织,行HE和Masson染色,通过酶联免疫吸附法(ELISA)测定肺组织IL-17、IL-6、肿瘤坏死因子-α(TNF-α)含量,Western blot分析肺组织胞核核因子-κB(NF-κB)p65以及细胞Ⅰ型胶原(ColⅠ)、Ⅲ型胶原(ColⅢ)蛋白表达情况,荧光实时定量PCR检测肺组织ColⅠ、ColⅢmRNA表达水平,分离血清,采用ELISA检测血清Ⅰ型前胶原羧基端前肽(PICP)、Ⅲ型前胶原氨基端前肽(PIIINP)浓度。结果 IL-17m Ab组肺泡炎症和肺纤维化程度明显轻于模型组及非特异性Ig G组(P0.01)。模型组和非特异性Ig G组肺组织IL-17、IL-6、TNF-α含量、胞核NF-κB p65蛋白表达、ColⅠ、ColⅢmRNA和蛋白表达以及血清PICP、PIIINP浓度较正常对照组及假手术组明显升高(P0.01)。经IL-17 m Ab处理后,上述指标相比模型组和非特异性IgG组明显降低(P0.01)。但非特异性Ig G组与模型组以及假手术组与正常对照组上述指标比较无差异(P0.05)。结论 IL-17 mAb通过下调NF-κB表达,抑制肺组织炎症反应及减少胶原蛋白合成,对肺纤维化大鼠产生保护作用。
[Abstract]:Objective to investigate the protective effect of interleukin (IL)-17 monoclonal antibody (m Ab) on bleomycin-induced pulmonary fibrosis in rats. Methods Seventy-five SD rats were randomly divided into normal control group, sham operation group, model group, non-specific Ig G group, IL-17 m Ab group and 15 rats in each group. In the sham operation group, the same amount of saline was injected into the trachea. The latter two groups were injected with nonspecific IgG,IL-17 mAb caudal vein on day 7, 14 and 21, respectively, and the other three groups were given the same amount of normal saline tail vein injection. All the rats were killed on d28, the lung tissue was taken and stained with HE and Masson. The expression of nuclear factor- 魏 B (NF- 魏 B) p65 and collagen 鈪，

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