Mechanism and protective effect of ulinastatin on vascular endothelial cells in sepsis rats
10.13699/j.cnki.1001-6821.2016.08.016
- VernacularTitle:乌司他丁对脓毒症大鼠血管内皮细胞损伤保护作用及机制研究
- Author:
Chu-Ming FAN
1
;
Xin-Yue YANG
;
Jing-Yu REN
;
Hong-Bo ZHANG
;
Jin RU
;
Qing-Ning CHEN
Author Information
1. 云南省第一人民医院 重症医学科
- Keywords:
ulinastatin;
sepsis;
vascular endothelial cell;
inflammation;
apoptosis
- From:
The Chinese Journal of Clinical Pharmacology
2016;32(8):723-726
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism and protective effect of ulinastatin on vascular endothelial cells ( VEC) in sepsis rats.Methods Forty SD male rats were randomly divided into four groups:sham oper-ation group, model group and low and high dose test groups ( ulinastatin, 10 ×104 ,20 ×104 U? kg -1 ) .The sepsis rat models were established with cecal ligation and puncture ( CLP).The level of tumor nuclear fac-tor-α( TNF-α) , interleukin 1β( IL-1β) and IL-6 in serum was assayed by enzyme linked immunosorbent assay method.The level of ni-trogen ( NO) and inducible nitric oxide synthase ( iNOS) was determina-ted by kits.VEC apoptosis was detected by flow cytometry.The activity of cysteinyl aspartate specific proteinase 3 ( Caspase 3) was measured by spectrophotometry.The expression of B-cell lymphoma-2 ( Bcl-2 ) , Bcl-2 associated X protein ( Bax ) and the activation of nuclear factor kappa B ( NF -κB ) signal pathway were assayed by Western blot. Results Compared with sham operation group, the level of TNF-α, IL-1β, IL-6, NO, iNOS was higher, the number of apoptotic VEC was higher, the activity of Caspase 3 and the expression of Bax was higher, the expression of Bcl-2 was lower, the phosphorylation of NF -κB p65 and IκBαwas higher in the model group, the difference was significant ( all P<0.01) .Compared with model group, low and high dose test groups could inhibit the change, the difference was significant (P<0.05).The ratio of Caspase 3 activity was (1.00 ±0.21,3.70 ±0.25,1.83 ±0.14,1.53 ±0.13). Conclusion These results suggested ulinastatin inhibited the injury of VEC in sepsis rats via resisting to inflammation and VEC apoptosis, which might be associated with NF-κB signal pathway.
