[Inhibitive effect of exogenous carbon monoxide-releasing molecules 2 on tissue factor expression in sepsis].
OBJECTIVE
To explore the inhibitive effects of exogenous carbon monoxide-releasing molecules 2 (CORM-2) on expression of tissue factor (TF) in sepsis.


METHODS
Human umbilical vein endothelial cells (HUVEC) were cultured with trypsin digestion method, which were divided into NC group (with normal treatment), LPS group (with culture of 10 microg/mL LPS), LD group (with 10 microg/mL LPS and DMSO in co-culture), LC1 group (with 10 microg/mL LPS and 10 micromol/L CORM-2 in co-culture), LC2 group (with 10 microg/mL LPS and 50 micromol/L CORM-2 in co-culture), LC3 group (with 10 microg/mL LPS and 100 micromol/L CORM-2 in co-culture). After culture for 4 hours, TF activity, TF protein expression, nuclear factor-kappaB (NF-kappaB) activity were examined. Forty-five C57 BL/6 male mice were randomly divided into NC (without treatment, n = 5), CLP (n = 5) and CLP + CORM-2 (with treatment of 8 mg/kg CROM-2 after CLP, n = 5) groups. The serum samples in CLP, CLP + CORM-2 groups were collected at 2, 6, 12 and 24 post operation hour ( POH, 5 mice at each time point) for determination of TF and TFPI levels,which were also examined in NC group.


RESULTS
Compared with those of NC group, TF activity increased (P < 0.01) , TF protein expression and NF-KB activity also increased in LPS group. Compared with those of LPS group, above indices were decreased in LC1, LC2, LC3 groups. The serum level of TF in CLP group at 6 POH was higher than that of NC group (80.0 +/- 11.9 pg/mL vs 58.4 +/- 6.9 pg/mL, P < 0.05), peaked at 12 POH, and still higher than that of NC group at 24 POH, while the serum level of TFPI showed no obvious difference in NC and CLP groups. Compared with that of NC group, TFPI levels obviously increased in CLP + CORM-2 group at 6, 12 POH (23.7 +/-3.5 ng/mL, 24.4 +/- 5.0 ng/mL vs 12.4 +/- 2.8 ng/mL, P < 0.05).


CONCLUSIONS
Exogenous CORM can obviously inhibit TF and NF-KB activity,decrease TF protein expression. Meanwhile, it can also decrease serum level of TF, and increase serum level of TFPI, preventing activation of procoagulant system, balancing procoagulant and anticoagulant system in sepsis.
Department of Burns and Plastic Surgery, the Affiliated Hospital to Jiangsu University, Zhenjiang 212001, China.
Bing-Wei
BW
Sun
Geng-Sheng
GS
Shi
Ping
P
Zhang
Xiang-Qian
XQ
Zou
Xi
X
Chen
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D018805:Sepsis / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
D008074:Lipoproteins; D016328:NF-kappa B; D009942:Organometallic Compounds; C051928:lipoprotein-associated coagulation inhibitor; C447082:tricarbonyldichlororuthenium (II) dimer; D013925:Thromboplastin