TanshinoneⅡA protects acute lung injury in septic mice by regulating neutrophil extracellular traps

Xiaohui ZHANG; Congmin CHEN; Xinyun DING; Xupeng DONG; Yuqing MA

doi:10.16016/j.2097-0927.202206077

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TanshinoneⅡA protects acute lung injury in septic mice by regulating neutrophil extracellular traps

Basic Medicine | 更新时间：2026-01-09

- TanshinoneⅡA protects acute lung injury in septic mice by regulating neutrophil extracellular traps
- Journal of Army Medical University Vol. 45, Issue 1, Pages: 38-44(2023)
- 作者机构：
  
  1.730000 兰州，兰州大学第一临床医学院
  2.730000 兰州，兰州大学第一医院麻醉科
- 作者简介：
- 基金信息：
  
  the Natural Science Foundation of Gansu Province(21JRIRA077)
- DOI：10.16016/j.2097-0927.202206077
  CLC： R285.5;R563.9;R631.2
- Received：13 June 2022，
  
  Revised：2022-07-31，
  
  Published：15 January 2023
- 稿件说明：
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Xiaohui ZHANG, Congmin CHEN, Xinyun DING, et al. TanshinoneⅡA protects acute lung injury in septic mice by regulating neutrophil extracellular traps[J]. Journal of Army Medical University, 2023, 45(1): 38-44.
DOI：

Xiaohui ZHANG, Congmin CHEN, Xinyun DING, et al. TanshinoneⅡA protects acute lung injury in septic mice by regulating neutrophil extracellular traps[J]. Journal of Army Medical University, 2023, 45(1): 38-44. DOI： 10.16016/j.2097-0927.202206077.

摘要

目的

研究丹参酮ⅡA(tanshinoneⅡA，TanⅡA)对脓毒症小鼠急性肺损伤(acute lung injury，ALI)作用，并探讨其对中性粒细胞胞外诱捕网(neutrophil extracellular traps，NETs)的影响及可能机制。

方法

采用腹腔注射脂多糖(lipopolysaccharide，LPS)建立小鼠脓毒症模型。雄性6~8周龄C57BL/6小鼠30只，随机数字表法分为5组(

=6)：①正常组(Nor组)；②脂多糖组(LPS组，腹腔注射LPS 10 mg/kg)；③丹参酮ⅡA组(LPS+TanⅡA组，LPS前30 min腹腔注射TanⅡA 30 mg/kg)；④LY294002组(LPS+LY294002组，提前注射LY294002 30 mg/kg)；⑤二甲基亚砜组(LPS+DMSO组，提前注射给药组等量DMSO)。造模12 h取材，计算肺系数，HE染色观察肺组织病理变化，ELISA检测肺组织炎症因子IL-1β、IL-10水平和NETs标志物MPO-DNA复合物、瓜氨酸化组蛋白H3(Cit H3)水平，Western blot检测PI3K/AKT信号通路的磷酸化水平。

结果

相较于Nor组，LPS组肺系数增加，HE染色显示肺组织受损，肺组织IL-1β水平升高(

0.05)，IL-10水平下降(

0.05)，MPO-DNA复合物、Cit H3均显著增加(

0.05)，p-PI3K和p-AKT水平升高(

0.05)。相较于LPS组，LPS+TanⅡA组和LPS+LY294002组肺系数降低，HE染色及肺损伤Smith评分显示肺组织病理损伤情况

减轻，肺组织IL-1β水平增加(

0.05)，IL-10水平降低(

0.05)，MPO-DNA复合物、Cit H3显著减少(

0.05)，p-PI3K和p-AKT水平降低(

0.05)。

结论

丹参酮ⅡA可以减轻脓毒症ALI，其机制可能是通过抑制PI3K/AKT信号通路，调控NETs水平，减轻炎症反应。

Abstract

Objective

To observe the effect of tanshinoneⅡA (TanⅡA) on acute lung injury (ALI) in septic mice

and to explore its effect on neutrophil extracellular traps (NETs) and its possible mechanism.

Methods

A mouse model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 10 mg/kg. Thirty male C57BL/6 mice aged 6~8 weeks were randomly divided into 5 groups (n=6): Normal group (Nor group)

LPS group

LPS+TanⅡA group (30 mg/kg TanⅡA was injected intraperitoneally 30 min before LPS injection)

LPS+LY294002 group (pre-injection of 30 mg/kg LY294002)

and LPS+DMSO group (pre-injection of the same amount of DMSO). At 12 h after modeling

the lung tissues were collected

lung coefficients were calculated

and pathological changes of lung tissue were observed with HE staining. ELISA was used to detect the levels of inflammatory factors IL-1β and IL-10 and NETs markers MPO-DNA complex and citrolinated histone H3 (Cit H3) in lung tissue. Western blotting was applied to detect the phosphorylation of the PI3K/AKT signaling pathway.

Results

Compared with the Nor group

the LPS group had an increased lung coefficient

significantly damaged lung tissue

increased levels of IL-1β (

0.05) and decreased level of IL-10 (

0.05)

and elevated MPO-DNA complex and Cit H3 levels (

0.05) as well as the levels of p-PI3K and p-AKT (

0.05). While

the above conditions were much better in the LPS+TanⅡA group and the LPS+LY294002 group than the LPS group

with decreased l

ung coefficient

alleviated lung injury by HE staining and Smith scores

increased level of IL-1β and decreased IL-10 level in the lung tissue (

0.05)

reduced levels of MPO-DNA complex and Cit H3 (

0.05) and p-PI3K and p-AKT (

0.05).

Conclusion

TanⅡA can alleviate sepsis-induced ALI

and its mechanism may be through inhibiting PI3K/AKT signaling pathway

regulating the level of NETs

and thus reducing the inflammatory response.

关键词

Keywords

references

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