PMID- 29920028
OWN - NLM
STAT- MEDLINE
DCOM- 20180730
LR  - 20181202
IS  - 2095-4352 (Print)
VI  - 28
IP  - 5
DP  - 2016 May
TI  - [Role of Rho/ROCK signaling pathway in the protective effects of hydrogen against 
      acute lung injury in septic mice].
PG  - 401-6
AB  - OBJECTIVE: To investigate the role of Rho/ROCK signaling pathway in the 
      protective effects of hydrogen gas (H2) on acute lung injury (ALI) in a mouse 
      model of sepsis. METHODS: Eighty male C57BL/6 mice were randomly divided into 
      four groups (n =20 per group):sham surgery group,H2 control group (sham + H2 
      inhalation),sepsis model group and H2 treatment group (sepsis + H2 
      inhalation).The mouse model of sepsis was created by cecal ligation puncture 
      (CLP),and the mice in sham surgery group didn't undergo cecal ligation and 
      puncture.The mice in the H2 inhalation groups received inhalation of 2％ H2 for 1 
      hour at 1 hour and 6 hours after CLP or sham surgery,respectively.Ten mice in 
      each group were selected and subjected to Evans blue (EB) test to evaluate the 
      pulmonary endothelial permeability at 24 hours after CLP operation.The rest of 10 
      mice in each group were sacrificed at 24 hours after CLP operation,the 
      bronchoalveolar lavage fluid (BALF) was collected for the measurement of protein 
      concentration,tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1 beta) 
      content,and polymorphonuclear neutrophils (PMN)counts.The lung tissues were 
      obtained to determine the content of malonaldehyde (MDA) and the activity of 
      superoxide dismutase (SOD),the wet/dry lung weight ratio (W/D) was calculated,the 
      lung pathological changes in hematoxylin and eosin (HE) stained sections were 
      evaluated under a light microscope,the activity of Rho/ROCK signaling pathway and 
      expression of zonula occluden 1 (ZO-1) were detected by Western Blot,and the 
      distribution and expression of ZO-1 were also examined by immunofluorescence 
      staining. RESULTS: There was no statistical difference in the above indexes 
      between the sham surgery group and the H2 control group.Compared with the sham 
      surgery group,the sepsis group demonstrated significant increases in the 
      concentrations of protein, TNF-alpha,IL-1 beta and PMN counts in BALF, the lung EB and 
      MDA content, W/D ratio, the ratio of Rho-GTP/total Rho,the expressions of ROCK1 
      and ROCK2,the ratio of phosphorylated-myosine phosphatae targeting subunit 1 
      (p-MYPT1)/MYPT1,and significant decreases in the lung SOD activity and ZO-1 
      expression. Compared with the sepsis group, the H2 treatment group showed 
      statistically significant decreases in the concentrations of protein, TNF-alpha,IL-1 
      beta,PMN counts in BALF [protein (g/L):3.12 +/- 0.33 vs.6.37+/-0.56,TNF-o(ng/L):128.45+/- 
      17.33 vs.563.83+/-61.72,IL-1beta (ng/L):75.76+/- 14.35 vs.245.52+/-30.56,PMN counts (x 
      105/L):7.46+/- 1.34 vs.18.55+/- 5.73],and permeability of lung [EB concentration 
      (mug/g):73.33+/-6.98vs.144.83+/- 12.38],the lung MDA content (mmol/g:3.66+/-0.53 
      vs.6.04+/- 1.13),the lung W/D ratio (5.02+/- 0.34 vs.7.26 +/-0.56),the ratio of 
      Rho-GTP/total Rho, the expressions of ROCK1 and ROCK2,the ratio of p-MYPT1/MYPT1 
      [Rho-GTP/total Rho:(43.12 +/- 4.69)％ vs.(68.82+/- 5.44)％,ROCK1 (gray value):2.42 +/- 
      0.42 vs.6.03 +/- 0.64,ROCK2(gray value):2.56+/- 0.52 vs.4.85 +/- 
      0.53,p-MYPT1/MYPT1:(57.83 +/- 8.67)％ vs.(112.50+/- 13.43)％],and statistically 
      significant increases in the lung SOD activity (kU/g:18.58+/- 1.68 vs.13.31+/-2.20) 
      as well as the expression of ZO-1 (gray value:0.61 +/- 0.07 vs.0.32 +/- 
      0.06,fluorescence intensity:0.77 +/- 0.06 vs.0.54 +/- 0.05;all P ＜ 0.05). Moreover, 
      lung HE staining showed that there were obvious lung injuries in the sepsis group 
      which were alleviated in the H2 treatment group. CONCLUSION: H2 could improve 
      endothelial permeability and suppress inflammation and oxidative stress to 
      alleviate ALI in septic mice through inhibition of Rho/ROCK signaling pathway.
FAU - Zhang, Hongtao
AU  - Zhang H
FAU - Liu, Liagling
AU  - Liu L
FAU - Yu, Yang
AU  - Yu Y
FAU - Sun, Zhe
AU  - Sun Z
FAU - Liang, Yu
AU  - Liang Y
FAU - Yu, Yonghao
AU  - Yu Y
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
JT  - Zhonghua wei zhong bing ji jiu yi xue
JID - 101604552
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 7YNJ3PO35Z (Hydrogen)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Acute Lung Injury/metabolism/*prevention & control
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid
MH  - Disease Models, Animal
MH  - Hydrogen/*pharmacology
MH  - Inflammation
MH  - Interleukin-1beta
MH  - Lung
MH  - Male
MH  - Malondialdehyde
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neutrophils
MH  - Oxidative Stress
MH  - Sepsis
MH  - *Signal Transduction
MH  - Tumor Necrosis Factor-alpha
MH  - rho-Associated Kinases/*physiology
EDAT- 2016/05/01 00:00
MHDA- 2018/07/31 06:00
CRDT- 2018/06/20 06:00
PHST- 2018/06/20 06:00 [entrez]
PHST- 2016/05/01 00:00 [pubmed]
PHST- 2018/07/31 06:00 [medline]
PST - ppublish
SO  - Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016 May;28(5):401-6.