Xuebijing Injection Ameliorates H<sub>2</sub>S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression

Ping GENG; Bing-yu LING; Hong-liang ZHANG; Jia-li XIONG; Ying WANG; Fen YU; Ding-yu TAN; Ji-yang XU; Hui-hui WANG

doi:10.1007/s11655-021-3344-3

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Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression

Original Article | Updated：2022-02-22

- Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression
- Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression
- Chinese Journal of Integrative Medicine 2022年28卷第2期页码：116-123
- Affiliations：
  
  1.Department of Emergency, Clinical Medical College of Yangzhou University, Northern Jiangsu People's Hospital,Yangzhou, Jiangsu Province (225001), China
  2.The First Clinical Medical College of Dalian Medical University, Dalian,Liaoning Province (116044), China
- Author bio：
  
  WANG Hui-hui, E-mail: wanghuihui19891021@163.com
- Funds：
  
  the Science and Technology Project of Jiangsu Traditional Chinese Medicine Bureau(YB2017076)
- DOI：10.1007/s11655-021-3344-3
  中图分类号：
- 纸质出版日期：2022-02-01，
  
  网络出版日期：2021-12-07，
  
  录用日期：2021-04-28
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Ping GENG, Bing-yu LING, Hong-liang ZHANG, 等. Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression[J]. Chinese Journal of Integrative Medicine, 2022,28(2):116-123.

Ping GENG, Bing-yu LING, Hong-liang ZHANG, et al. Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression[J]. Chinese Journal of Integrative Medicine, 2022,28(2):116-123.
Ping GENG, Bing-yu LING, Hong-liang ZHANG, 等. Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression[J]. Chinese Journal of Integrative Medicine, 2022,28(2):116-123. DOI： 10.1007/s11655-021-3344-3.

Ping GENG, Bing-yu LING, Hong-liang ZHANG, et al. Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression[J]. Chinese Journal of Integrative Medicine, 2022,28(2):116-123. DOI： 10.1007/s11655-021-3344-3.

摘要

目的:

探讨血必净注射液 (XBJ) 对硫化氢 (H

S) 诱导的急性呼吸窘迫综合征 (ARDS) 的肺内皮屏障功能的保护作用及其机制.

方法:

将SD大鼠暴露于H

S (300ppm) 中建立ARDS大鼠模型

将人肺微血管内皮细胞 (HPMEC) 与NaHS (H

S的供体

500μmol/L) 共同孵育建立ARDS细胞模型. 大鼠和细胞模型分别用H

S和XBJ处理. 在体内实验中通过苏木精-伊红染色、免疫组织化学染色、透射电镜和干/湿比来观察H

S诱导的ARDS模型中的肺组织情况. 然后分别在体内和体外实验中评估claudin-5、磷酸化蛋白激酶B (p-AKT/t-AKT) 和p-叉头框转录因子O1 (FoxO1/t-FoxO1) 表达水平. 在细胞模型中通过测量细胞旁通透性和跨上皮电阻 (TEER) 以评估内皮屏障功能.

结果:

通过形态学观察显示XBJ能改善H

S诱导的大鼠ARDS的肺损伤. NaHS处理的人肺微血管内皮细胞中跨上皮电阻降低和细胞旁通透性增加

而XBJ可以逆转以上现象 (

0.05) . 磷脂酰肌醇3-激酶PI3K/AKT/FoxO1通路抑制剂LY294002阻断XBJ的保护作用 (

0.05) . 此外

XBJ可提高体内剂体外claudin-5、p-AKT和p-FoxO1蛋白的表达水平 (

0.05) .

结论:

血必净注射液通过PI3K/AKT/FoxO1信号通路促进claudin-5的表达

从而改善H

S诱导的ARDS.

Abstract

Objective:

To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H

S)-induced acute respiratory distress syndrome (ARDS).

Methods:

Sprague-Dawley rats were exposed to H

S (300 ppm) to establish ARDS model

while human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H

S donor

500 μmol/L) to establish cell model. H

S and XBJ were concurrently administered to the rat and cell models. Lung hematoxylin and eosin staining

immunohistochemistry

transmission electron microscopy and wet/dry ratio measurement were used to confirm ARDS induced by H

in vivo

. The expression levels of claudin-5

phosphorylated protein kinase B (p-AKT)/t-AKT and p-forkhead box transcription factor O1 (FoxO1)/t-FoxO1

in vivo

and

in vitro

were also assessed. Paracellular permeability and transepithelial electrical resistance (TEER) were measured to evaluate endothelial barrier function in the cell model.

Results:

The morphological investigation showed that XBJ attenuated H

S-induced ARDS in rats. XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs (

0.05). The protective effects of XBJ were blocked by LY294002

a phosphatidylinositol 3-kinase (PI3K)/AKT/FoxO1 pathway antagonist (

0.05). Furthermore

XBJ promoted the expression of claudin-5 and increased the levels of p-AKT and p-FoxO1

in vivo

and

in vitro

(

0.05).

Conclusion:

XBJ ameliorated H2S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway.

关键词

Keywords

acute respiratory distress syndromeXuebijing Injectionhydrogen sulfideclaudin-5phosphatidylinositol 3-kinase

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Xuebijing Injection Ameliorates H2S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression

Xuebijing Injection Ameliorates H2S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression

DOI：10.1007/s11655-021-3344-3

摘要

Abstract

关键词

Keywords

references

Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression

Xuebijing Injection Ameliorates H₂S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression