实用医学杂志 ›› 2021, Vol. 37 ›› Issue (23): 2967-2970.doi: 10.3969/j.issn.1006⁃5725.2021.23.002

• 基础研究 • 上一篇    下一篇

miR-132基于PGC⁃1α/SIRT3信号通路对肺炎链球菌诱慢性阻塞性肺疾病急性加重期大鼠的干预作用

张松松1 刘曼莉2 王金龙1 潘渝1 施贤清1   

  1. 贵州省人民医院1 重症医学科,2 重症监护室(贵阳550002)

  • 出版日期:2021-12-10 发布日期:2021-12-10
  • 通讯作者: 施贤清 E⁃mail:ikkit58@163.com
  • 基金资助:
    国家自然科学基金项目(编号:81860273);贵州省人民医院国家自然科学基金培育基金(编号:[2018]5764⁃09)

Effect of miR⁃132 on streptococcus pneumonia⁃induced AECOPD rats based on PGC⁃1α/SIRT3 signaling pathway 

ZHANG Songsong*,LIU Manli,WANG Jinlong,PAN Yu,SHI Xianqing.   

  1. Department of Critical Care Medicine,Guizhou Provincial People′s Hospital,Guiyang 550002,China

  • Online:2021-12-10 Published:2021-12-10
  • Contact: SHI Xianqing E⁃mail:ikkit58@163.com

摘要:

目的 分析微小 RNA⁃132(miR⁃132)经过氧化物酶体增殖物受体 γ 共激活因子 1α/去乙酰化 3(PGC⁃1α/SIRT3)信号通路对肺炎链球菌诱慢性阻塞性肺疾病急性加重期(AECOPD)大鼠的干预作 用,为临床上肺炎链球菌所致的 AECOPD 治疗提供新方向。方法 选取 60 只大鼠,15 只作为 A 组(正常), 其余 45 只构建肺炎链球菌所诱导的 AECOPD 模型,完成后分为 B 组、C 组、D 组各 15 只。构建 miR⁃132 拟物、miR⁃132 抑制物,将稀释后的 miR⁃132 模拟物、miR⁃132 抑制物分别注射于 D 组、C 组肺部,A 组、B 注射同剂量生理盐水。对比分析各组肺功能相关指标、外周血白细胞计数、中性粒细胞百分比计数、气道炎症反应情况以及肺组织 PGC⁃1α/SIRT3 信号通路蛋白表达情况。结果 A 组相比,B 组、C 组大鼠肺 组织 miR⁃132 表达降低,D 组大鼠肺组织 miR⁃132 表达升高,差异具有统计学意义(P<0.05)。与 A 组相 比,B 组、C 组、D FEV0.3/FVC、PIF、PEF、肺组织 PGC⁃1α、SIRT3 蛋白表达量均降低,白细胞总数、中性粒 细胞百分比计数、IL⁃1β、IL⁃6、TNF⁃α 水平均升高,差异具有统计学意义(P<0.05)。与 B 组相比,C FEV0.3/FVC、PIF、PEF、肺组织 PGC⁃1α、SIRT3 蛋白表达量均降低,白细胞总数、中性粒细胞百分比计数、 IL⁃1β、IL⁃6、TNF⁃α 水平均升高,差异具有统计学意义(P<0.05)。与 B 组相比,D FEV0.3/FVC、PIF PEF、肺组织 PGC⁃1α、SIRT3 蛋白表达量均升高,白细胞总数、中性粒细胞百分比计数、IL⁃1β、IL⁃6、TNF⁃α 水平均降低,差异具有统计学意义(P<0.05)。与 C 组相比,D FEV0.3/FVC、PIF、PEF、肺组织 PGC⁃1α SIRT3 蛋白表达量均升高,白细胞总数、中性粒细胞百分比计数、IL⁃1β、IL⁃6、TNF⁃α 水平均降低,差异具有统计学意义(P<0.05)。结论 miR⁃132过表达可改善肺炎链球菌诱AECOPD 大鼠气道炎症,修复肺损伤, 分析其机制可能与激活PGC⁃1α/SIRT3信号通路PGC⁃1α 上调SIRT3表达相关。

关键词:

微小 RNA?132, 过氧化物酶体增殖物受体 γ 共激活因子, 去乙酰化酶 3, 肺炎链球菌, 慢性阻塞性肺疾病, 肺功能 ,

Abstract:

Objective To explore the effect of Microrna⁃132(mir⁃132)on rats with acute exacerbation of chronic obstructive pulmonary disease (AECOPD induced by Streptococcus pneumoniae through the oxidase proliferator receptor γ Coactivator 1 α/Deacetylase 3(PGC⁃1)α/SIRT3 signal pathway and to provide a new direction for the clinical treatment of AECOPD caused by streptococcus pneumoniae. Methods Sixty rats were selected 15 were included in group A(normal group),and the remaining 45 were used to construct the AECOPD model induced by Streptococcus pneumoniae. After completion,they were divided into group B,C,and D,with 15 rats in each. The miR⁃132 mimics and miR⁃132 inhibitors were constructed,and the diluted miR⁃132 mimics and miR⁃ 132 inhibitors were injected into the lungs of group D and C,respectively,and group A and B were injected with the same dose of normal saline. Lung function,peripheral blood leukocytes,neutrophil percentage counts,airway inflammation,and PGC ⁃1α/SIRT3 signaling pathway protein expression in lung tissues were compared and ana⁃ lyzed. Results Compared with that in group A,the expression of miR ⁃132 in group B and C decreased,while that in group D increased,and the difference was statistically significant(P < 0.05). Compared with those in group A,FEV0.3/FVC,PIF,PEF,lung tissue PGC⁃1α,and SIRT3 protein expression in groups B,C,and Ddecreased;the total number of white blood cells,neutrophil percentage count,and the level of IL⁃1β,IL⁃6,and TNF ⁃ α increased,and the difference was statistically significant(P < 0.05). Compared with those in group B FEV0.3/FVC,PIF,PEF,lung tissue PGC⁃1α,and SIRT3 protein expression in group C were all reduced;the total number of white blood cells ,neutrophil percentage count ,and the level of IL⁃1 β ,IL⁃6 ,and TNF⁃ α increased,and the difference was statistically significant(P < 0.05). Compared with those in group B,FEV0.3/ FVC,PIF,PEF,lung tissue PGC ⁃1α,and SIRT3 protein expression in group D increased;the total number of white blood cells,neutrophil percentage count,and the level of IL⁃1β,IL⁃6,and TNF⁃ α decreased,and the difference was statistically significant(P < 0.05). Compared with those in group C,FEV0.3/FVC,PIF,PEF,lung tissue PGC⁃1α,and SIRT3 protein expression increased in group D;total number of white blood cells,neutrophil percentage count,and the level of IL⁃1β,IL⁃6,and TNF⁃α decreased,and the difference was statistically signifi⁃ cant(P < 0.05). Conclusion Overexpression of mir⁃132 can improve airway inflammation and repair lung injury in AECOPD rats induced by Streptococcus pneumoniae. Its mechanism may be related to activation of PGC ⁃ 1α/ SIRT3 signaling pathway and up⁃regulation of SIRT3 expression.

Key words:

microRNA?132, peroxisome proliferator receptor γ coactivator 1α, deacetylase 3, strep? tococcus pneumoniae, chronic obstructive pulmonary disease, pulmonary function