PMID- 20079161
OWN - NLM
STAT- MEDLINE
DCOM- 20100524
LR  - 20100118
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 122
IP  - 20
DP  - 2009 Oct 20
TI  - Antithrombin-III without concomitant heparin improves endotoxin-induced acute 
      lung injury rats by inhibiting the activation of mitogen-activated protein 
      kinase.
PG  - 2466-71
AB  - BACKGROUND: Antithrombin-III (AT-III), the major inhibitor of thrombin in plasma, 
      also has anti-inflammation property and might have positive effect on sepsis. The 
      present study aimed to investigate the effects of AT-III on inflammatory reaction 
      and pulmonary protection in endotoxin-induced acute lung injury (ALI) rat. 
      METHODS: Sixty male Sprague-Dawley rats were randomly assigned equally to normal 
      control group, ALI group, AT-III treatment group, AT-III + heparin treatment 
      group, and heparin treatment group. The pulmonary vascular permeability index 
      (PVPI) was measured by single nuclide tracer technique. The activity of AT-III in 
      plasma was determined by the method of synthetic chromogenic substrata. Tumor 
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels in serum were 
      determined by enzyme-linked immunosorbent assay. The expressions of lung tissue 
      mitogen-activated protein kinases (ERK1/2, P38 and JNK MAPK) were determined by 
      Western blotting. RESULTS: Rats had significantly improved lung histopathology in 
      the AT-III treatment group and heparin treatment group compared with the ALI 
      group. The PVPI of the ALI group was 0.38 + or - 0.04, significantly higher than 
      that of the normal control group (0.20 + or - 0.02, P < 0.01), AT-III treatment 
      group (0.30 + or - 0.04, P < 0.01) and heparin treatment group (0.28 + or - 0.04, 
      P < 0.01) respectively. There were no significant differences of PVPI in the ALI 
      group and AT-III + heparin treatment group. The activity of AT-III in plasma in 
      the ALI group was (76 + or - 8)%, significantly lower than that of the normal 
      control group ((96 + or - 11)%, P < 0.05) and AT-III treatment group ((105 + or - 
      17)%, P < 0.05) respectively. The serum levels of TNF-alpha and IL-6 of the ALI 
      group were (2.770 + or - 0.373) microg/L and (1.615 + or - 0.128) ng/ml 
      respectively, significantly higher than those of the normal control group ((0.506 
      + or - 0.093) microg/L and (0.233 + or - 0.047) ng/ml respectively, all P < 
      0.01), AT-III treatment group ((1.774 + or - 0.218) microg/L and (1.140 + or - 
      0145) ng/ml respectively, all P < 0.01) and heparin treatment group ((1.924 + or 
      - 0.349) microg/L and (1.223 + or - 0.127) ng/ml respectively, all P < 0.01). The 
      lung tissue levels of phospho-ERK1/2 and phospho-P38 MAPK expressions were 
      markedly higher in the ALI group than in the normal control group, AT-III 
      treatment group and heparin treatment group respectively. CONCLUSIONS: AT-III 
      without concomitant heparin inhibited the activation of ERK1/2 and P38 MAPK, 
      down-regulated the levels of downstream cytokines TNF-alpha and IL-6, relieved 
      endothelial permeability, and improved the ALI in endotoxin-induced rats. It 
      might be helpful to administrate AT-III alone, not with concomitant heparin, to 
      those patients with ALI and sepsis.
FAU - Sun, Hui-ming
AU  - Sun HM
AD  - Department of Respiratory Diseases, Clinical School of Nanjing University, 
      Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu 210002, 
      China.
FAU - Hong, Ling-zhi
AU  - Hong LZ
FAU - Shen, Xiao-kun
AU  - Shen XK
FAU - Lin, Xin-qing
AU  - Lin XQ
FAU - Song, Yong
AU  - Song Y
FAU - Shi, Yi
AU  - Shi Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Endotoxins)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acute Lung Injury/chemically induced/*drug therapy/*enzymology/pathology
MH  - Animals
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Antithrombin III/*therapeutic use
MH  - Endotoxins/*toxicity
MH  - Heparin/*therapeutic use
MH  - Lung/drug effects/metabolism/pathology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2010/01/19 06:00
MHDA- 2010/05/25 06:00
CRDT- 2010/01/19 06:00
PHST- 2010/01/19 06:00 [entrez]
PHST- 2010/01/19 06:00 [pubmed]
PHST- 2010/05/25 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2009 Oct 20;122(20):2466-71.