[1]刘理静,钱 红,尹辉明,等.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[J].中国药理学通报,2015,(11):1586-1591.[doi:10.3969/j.issn.1001-1978.2015.11.021]
 LIU Li-jing,QIAN Hong,YIN Hui-ming,et al.Protective effect of IL-17 monoclonal antibody on rats with pulmonary fibrosis and its partial mechanisms[J].Chinese Pharmacological Bulletin,2015,(11):1586-1591.[doi:10.3969/j.issn.1001-1978.2015.11.021]
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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()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2015年11期
页码:
1586-1591
栏目:
论 著
出版日期:
2015-11-30

文章信息/Info

Title:
Protective effect of IL-17 monoclonal antibody on rats with pulmonary fibrosis and its partial mechanisms
作者:
刘理静12钱 红1尹辉明2张 平3王在岩3肖 华3
1.湖南医药学院临床医学院,湖南 怀化 418000; 2. 湖南医药学院附属第一医院呼吸内科,湖南 怀化 418000; 3.南华大学附属第一医院呼吸内科,湖南 衡阳 421001
Author(s):
LIU Li-jing12 QIAN Hong1 YIN Hui-ming2 ZHANG Ping3 WANG Zai-yan3 XIAO Hua3
1.School of Clinical Medicine, Hunan University of Medicine, Huaihua Hunan 418000, China; 2. Dept of Respiration, the First Affiliated Hospital, Hunan University of Medicine, Huaihua Hunan 418000, China; 3.Dept of Respiration, the First Affiliated Hospital,University of South China, Hengyang Hunan 421001,China
关键词:
白介素-17单克隆抗体 肺纤维化 炎症反应 白介素-6 肿瘤坏死因子-α 核因子-κB Ⅰ型胶原 Ⅲ型胶原
Keywords:
IL-17 monoclonal antibody pulmonary fibrosis inflammatory response IL-6 TNF-α NF-κB Col Ⅰ Col Ⅲ
分类号:
R-332; R322.35; R392.11; R392.12; R563.13; R977.6
DOI:
10.3969/j.issn.1001-1978.2015.11.021
文献标志码:
A
摘要:
目的 探讨白介素(IL)-17单克隆抗体(mAb)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IgG组、IL-17 mAb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(Col Ⅰ)、Ⅲ型胶原(Col Ⅲ)蛋白表达情况,荧光实时定量PCR检测肺组织Col Ⅰ、Col Ⅲ mRNA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-17mAb组肺泡炎症和肺纤维化程度明显轻于模型组及非特异性IgG组(P<0.01)。模型组和非特异性IgG组肺组织IL-17、IL-6、TNF-α含量、胞核NF-κB p65蛋白表达、Col Ⅰ、Col Ⅲ mRNA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(P<0.01)。经IL-17 mAb处理后,上述指标相比模型组和非特异性IgG组明显降低(P<0.01)。但非特异性IgG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(P>0.05)。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:
Aim To explore the protective effects of interleukin-17(IL-17)monoclonal antibody(mAb)on bleomycin-induced pulmonary fibrosis rats and the related mechanisms. Methods Seventy-five male SD rats were randomly divided into normal control group, sham operation group, model group, non-specific IgG group and IL-17 mAb group. Each group included fifteen rats. Rats in the latter three groups were intratracheally administered with bleomycin A5 to establish pulmonary fibrosis model, whereas the ones in sham operation group were treated with the same volume of physiological saline. On day 7, 14 and 21, rats in non-specific IgG group and IL-17 mAb group were injected with non-specific IgG and IL-17 mAb,respectively,through the caudal vein.However,the ones in the other groups were administered with the same volume of physiological saline. All rats were sacrificed on day 28. Pulmonary tissues were then removed, and HE and Masson staining was performed. The contents of IL-17, IL-6 and tumor necrosis factor-α(TNF-α)in pulmonary tissues were measured by enzyme linked immunosorbent assay(ELISA). Western blot was used to analyze the pulmonary tissues protein expression of nuclear factor-κB(NF-κB)p65 in the nucleus as well as collagen type I(Col Ⅰ)and collagen type III(Col Ⅲ)in the whole cells. The levels of Col Ⅰ and Col Ⅲ in the pulmonary tissues were detected by fluorescence real-time quantitative PCR. Serum was separated, and the concentrations of procollagen type 1carboxyterminal propeptide(PICP)and procollagen type III aminoterminal propeptide(PIIINP)in serum were then measured by ELISA. Results The severity of alveolitis and pulmonary fibrosis was lower in IL-17 mAb group than that in model group and non-specific IgG group(P<0.01). In comparison with normal control group and sham operation group, pulmonary tissues IL-17, IL-6 and TNF-α contents, NF-κB p65 protein expression in the nucleus, Col Ⅰ and Col Ⅲ mRNA and protein levels, and serum PICP and PIIINP concentrations were significantly increased in model group and non-specific IgG group(P<0.01). Following treatment with IL-17 mAb,the above indicators were significantly decreased as compared to model group and non-specific IgG group(P<0.01). However, there was no significant difference in these indicators between non-specific IgG group and model group(P>0.05). Similar results were also seen between sham operation group and normal control group(P>0.05). Conclusion IL-17 mAb protects rats from pulmonary fibrosis by inhibiting inflammatory response via downregulating NF-κB expression and decreasing collagen synthesis in the pulmonary tissues.

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更新日期/Last Update: 1900-01-01