天津医药 ›› 2020, Vol. 48 ›› Issue (4): 258-262.doi: 10.11958/20192555

• 实验研究 • 上一篇    下一篇

中和白细胞介素-17对特发性肺纤维化小鼠胶原和凋亡相关因子表达的影响 #br#

赵铁军 1,宋桂芹 2,张浩婷 2,崔伟亮 2,黄勇 2,王文栋 2,张效云 2△
  

  1. 1河北北方学院生命科学研究中心(邮编075000),2生化教研室
  • 收稿日期:2019-08-20 修回日期:2020-01-14 出版日期:2020-04-15 发布日期:2020-06-23
  • 通讯作者: 张效云 E-mail:xyzonly928@163.com
  • 作者简介:赵铁军(1968),女,本科,副教授,主要从事呼吸系统疾病研究
  • 基金资助:
    河北省高等学校自然科学重点项目(ZD2017206

The effect of neutralizing interleukin-17 on the expressions of collagen and#br# apoptosis-related factors in model mice with idiopathic pulmonary fibrosis #br#

ZHAO Tie-jun1, SONG Gui-qin2, ZHANG Hao-ting2, CUI Wei-liang2,#br# HUANG Yong2, WANG Wen-dong2, ZHANG Xiao-yun2△ #br#   

  1. 1 Life Science Research Center, 2 Department of Biochemistry, Hebei North University, Zhangjiakou 075000, China
  • Received:2019-08-20 Revised:2020-01-14 Published:2020-04-15 Online:2020-06-23
  • Contact: ZHANG Xiao-yun E-mail:xyzonly928@163.com

摘要: 目的 探讨中和白细胞介素-17IL-17)对博来霉素所致特发性肺纤维化小鼠肺组织胶原和凋亡相关因
子表达的影响。
方法 32只雄性C57BL/6小鼠随机分为正常对照组、模型组、中和抗体组和抗体对照组。利用一
次性气管内灌注博来霉素(
5 U/kg)诱导特发性肺纤维化。中和抗体组和抗体对照组小鼠从造模后第 3 天起,每 4 d
尾静脉分别注射 IL-17 单克隆抗体和同型对照抗体,模型组和正常对照组则给予等量生理盐水。28 d后取肺组织,
通过
Masson 染色评价各组小鼠肺纤维化程度;实时荧光定量 PCR 法测定肺组织胶原型和mRNA 含量;
Western blot检测活化的半胱氨酸天冬氨酸蛋白酶(Cleaved-caspase-3Cleaved-caspase-9的表达水平。结果
模型组相比,中和抗体组肺纤维化程度显著下降(
P0.01),胶原型和mRNA表达明显下调(P0.01),Cleavedcaspase-3Cleaved-caspase-9蛋白的表达显著降低(P0.01),在模型组和抗体对照组间以上指标差异均无统计学意
义。
结论 中和IL-17可能通过调控凋亡信号Cleaved-caspase-3Cleaved-caspase-9蛋白的表达,改善肺纤维化。

关键词: 白细胞介素17, 细胞凋亡, 特发性肺纤维化, 半胱氨酸天冬氨酸蛋白酶, 胶原, 胶原, 博来霉素

Abstract: Objective To investigate the effect of neutralizing interleukin-17 (IL-17) on the expressions of collagen
and apoptosis-related factors in model mice with idiopathic pulmonary fibrosis induced by bleomycin.
Methods Thirtytwo male C57BL/6 mice were randomly divided into normal control group, model group, neutralizing antibody group and
antibody control group. The mouse model of idiopathic pulmonary fibrosis was induced by intratracheal infusion of bleomycin (BLM, 5 U/kg). Mice in the neutralizing antibody group and the antibody control group were injected with IL-17 monoclonal antibody or isotype control antibody through the caudal vein every 4 days from the day 3 after BLM instillation, and the
model group and the normal control group were given the same amount of normal saline. At the day 28, all mice were
euthanized, the lung fibrosis degree was assessed by Masson staining. The mRNA contents of collagen typeⅠand type Ⅲ in lung tissues were determined by real-time fluorescent quantitative PCR, and the expression levels of Cleaved-cysteinasparate protease (Cleaved-caspase)-3 and Cleaved-caspase-9 were detected by Western blot assay.
Results Compared with the model group, the degree of pulmonary fibrosis was significantly declined in the neutralizing antibody group (P0.01), the mRNA expressions of collagen typeⅠand type Ⅲ were obviously decreased (P0.01), and the protein expressions of Cleaved-caspase-3 and Cleaved-caspase-9 were markedly reduced (P0.01), but there were no significant differences in these data between model group and the antibody control group. Conclusion Neutralizing endogenous IL-17 may improve pulmonary fibrosis by regulating the expressions of Cleaved-caspase-3 and Cleaved-caspase-9 proteins.

Key words: interleukin-17, apoptosis, idiopathic pulmonary fibrosis, cystein-asparate protease, collagen type Ⅰ,
collagen type Ⅲ,
bleomycin

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