中国临床药理学杂志2016,Vol.32Issue(8):723-726,4.DOI:10.13699/j.cnki.1001-6821.2016.08.016
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
Mechanism and protective effect of ulinastatin on vascular endothelial cells in sepsis rats
摘要
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.关键词
乌司他丁/脓毒症/血管内皮细胞/炎症/凋亡Key words
ulinastatin/sepsis/vascular endothelial cell/inflammation/apoptosis分类
医药卫生引用本文复制引用
樊楚明,杨欣悦,任靖宇,张洪波,茹今,陈庆宁..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[J].中国临床药理学杂志,2016,32(8):723-726,4.基金项目
云南省科技厅昆明医科大学联合基金资助项目 ()