摘要
Objective:To investigate whether atractylenolide Ⅰ(ATL-Ⅰ) has protective effect on lipopolysaccharide(LPS)-induced disseminated intravascular coagulation(DIC) in vivo and in vitro,and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ treatment.Methods:New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6h at a rate of 600 μg/kg(10 mL/h).Similarly,in the treatment groups,1.0,2.0,or 5.0 mg/kg ATL-Ⅰ were given.Both survival rate and organ function were tested,including the level of alanine aminotransferase(ALT),blood urine nitrogen(BUN),and TNF-α were examined by ELISA.Also haemostatic and fibrinolytic parameters in serum were measured.RAW 264.7 macrophage cells were administered with control,LPS,LPS + ATL-Ⅰ and ATL-Ⅰ alone,and TNF-α,phosphorylation(P)-IκBα,phosphorylation(P)-NF-κB(P65) and NF-κB(P65) were determined by Western blot.Results:The administration of LPS resulted in 73.3%mortality rate,and the increase of serum TNF-α,BUN and ALT levels.When ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model,also improved the function of blood coagulation.And protein analysis indicated that ATL-Ⅰ remarkably protected liver and renal as decreasing TNF-α expression.In vitro,ATL-Ⅰ obviously decreased LPS-induced TNF-αproduction and the expression of P-NF-κB(P65),with the decrease of P-IκBα.Conclusions:ATL-Ⅰ has protective effect on LPS-induced DIC,which can elevate the survival rate,reduce organ damage,improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.
Objective:To investigate whether atractylenolide Ⅰ(ATL-Ⅰ) has protective effect on lipopolysaccharide(LPS)-induced disseminated intravascular coagulation(DIC) in vivo and in vitro,and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ treatment.Methods:New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6h at a rate of 600 μg/kg(10 mL/h).Similarly,in the treatment groups,1.0,2.0,or 5.0 mg/kg ATL-Ⅰ were given.Both survival rate and organ function were tested,including the level of alanine aminotransferase(ALT),blood urine nitrogen(BUN),and TNF-α were examined by ELISA.Also haemostatic and fibrinolytic parameters in serum were measured.RAW 264.7 macrophage cells were administered with control,LPS,LPS + ATL-Ⅰ and ATL-Ⅰ alone,and TNF-α,phosphorylation(P)-IκBα,phosphorylation(P)-NF-κB(P65) and NF-κB(P65) were determined by Western blot.Results:The administration of LPS resulted in 73.3%mortality rate,and the increase of serum TNF-α,BUN and ALT levels.When ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model,also improved the function of blood coagulation.And protein analysis indicated that ATL-Ⅰ remarkably protected liver and renal as decreasing TNF-α expression.In vitro,ATL-Ⅰ obviously decreased LPS-induced TNF-αproduction and the expression of P-NF-κB(P65),with the decrease of P-IκBα.Conclusions:ATL-Ⅰ has protective effect on LPS-induced DIC,which can elevate the survival rate,reduce organ damage,improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.
基金
funded by grants from the Science and Technology Planning Project of Guangdong Province(2014A020211022)
Science and Technology Planning Project of Guangzhou Province(201510010074)
