FOLLOWUS
Xuebijing Injection Ameliorates H2S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression
- Chinese Journal of Integrative Medicine Vol. 28, Issue 2, Pages: 116-123(2022)
- 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：
DOI：10.1007/s11655-021-3344-3
CLC：Published：01 February 2022，
Published Online：07 December 2021，
Accepted：28 April 2021
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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 28(2):116-123(2022)
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 28(2):116-123(2022) DOI： 10.1007/s11655-021-3344-3.
摘要
目的:
2
探讨血必净注射液 (XBJ) 对硫化氢 (H
2
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:
2
将SD大鼠暴露于H
2
S (300ppm) 中建立ARDS大鼠模型
将人肺微血管内皮细胞 (HPMEC) 与NaHS (H
2
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
2
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
2
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:
2
通过形态学观察显示XBJ能改善H
2
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 (
P
<
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 (
P
<
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 (
p
<
0.05) .
结论:
2
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
2
S诱导的ARDS.
Abstract
Objective:
2
To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H
2
S)-induced acute respiratory distress syndrome (ARDS).
Methods:
2
Sprague-Dawley rats were exposed to H
2
S (300 ppm) to establish ARDS model
while human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H
2
S donor
500 μmol/L) to establish cell model. H
2
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
2
S
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:
2
The morphological investigation showed that XBJ attenuated H
2
S-induced ARDS in rats. XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs (
P
<
0.05). The protective effects of XBJ were blocked by LY294002
a phosphatidylinositol 3-kinase (PI3K)/AKT/FoxO1 pathway antagonist (
P
<
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
(
P
<
0.05).
Conclusion:
2
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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