Therapeutic effect of Xuebijing injection on acute lung injury in a rat model of cecal ligation puncture
10.3760/cma.j.issn.1001-8050.2016.10.003
- VernacularTitle:血必净注射液对盲肠结扎穿孔脓毒症模型大鼠急性肺损伤的治疗作用
- Author:
Ning WANG
;
Xinchuan ZHENG
;
Xin LIU
;
Jiang ZHENG
- Publication Type:Journal Article
- Keywords:
Sepsis;
Acute lung injury;
Xuebijing injection
- From:
Chinese Journal of Trauma
2016;32(10):875-881
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic role of Xuebijing injection on acute lung injury (ALI) in a rat model of cecal ligation puncture (CLP) and the potential mechanism.Methods A total of 110 SD rats were divided into sham group (n =30),CLP group (n =40) and Xuebijing treatment group (n =40),according to the random number table.Survival was observed up to 7 days.Rats in each group were sacrificed 12 h after the CLP surgery.Blood samples were obtained by abdominal aorta puncture and inflammatory cytokines and blood gas were detected.Samples of the lung tissue were excised to measure mRNA expression of cytokines,activation of signaling molecules,wet to dry ratio and histopathological changes.Peripheral neutrophils were isolated in vitro and divided into negative control group,high-dose Xuebijing (1 ∶ 30 dilution) group,lipopolysaccharide (LPS,100 ng/ml) group,LPS plus low-,middle-and high-dose Xuebijing (1∶ 300,1∶ 100,1∶30 dilution respectively) groups.Supernatant levels of tumor necrosis factor (TNF-α),interleukin (IL)-6 and neutrophil elastase (NE) in each group were detected.Activation of intracellular signaling molecules was measured as well.Results In animal survival observation,the mortality was 65 ％ in CLP model group and reduced to 30％ in Xuebijing treatment group (P ＜ 0.01).Compared to sham group,serum levels of TNF-α,IL-6,PaCO2 and lactate in CLP group were increased markedly to (32.213 ± 9.802) pg/ml,(21.592 ± 5.427) ng/ml,(39.575 ± 5.295) mmHg and (3.438 ± 0.192) mmol/L respectively,mRNA expressions of TNF-α and IL-6 in CLP group were increased to 5.223 ±0.525 and 12.097 ±2.535 respectively,activation of IκB-α,p38,extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK)in CLP group were significantly up-regulated,and water content of rat lung tissue in CLP group were significantly increased to (78.226 ±0.894) ％ (all P ＜0.01).Moreover,histopathological appearance of bleeding,exudation and increased infiltration of neutrophils to the alveolar septum were detected in the lung tissue of CLP rats.Compared to CLP group,Xuebijing treatment reduced the serum levels of TNF-α [(21.592 ± 5.427)pg/ml],IL-6 [(2.252 ± 0.905) ng/m],PaCO2 [(34.088 ± 2.260) mmHg] and lactate [(2.563 ± 0.250)mmol/L],suppressed the up-regulation of TNF-α and IL-6 mRNA expressions [6.866 ± 1.604,3.398 ± 0.334],and reduced the water content of rat lung tissue [(77.159 ± 0.626)％] (P ＜0.05 or 0.01).Compared to CLP group,Xuebijing treatment ameliorated the histological appearance of ALI.In vitro study,negative control group and high-dose Xuebijing group showed basal levels of TNF-α,IL-6 and neutrophil elastase (NE).Levels of TNF-α,IL-6 and NE in cell supernatant were elevated in LPS group [(7 102.520 ± 528.026) pg/ml,(3 109.598 ± 191.291) pg/ml and (63.985 ± 2.823) ng/ml respectively],with significant differences from these detected in negative control group (P ＜0.01).While the release of TNF-α,IL-6 and NE was significantly inhibited in LPS plus middle-and high-dose Xuebijing groups,compared to LPS group (P ＜ 0.05 or P ＜0.01).LPS also increased the degradation of IκB-α and phosphorylation of p38 and ERK in neutrophils,and Xuebijing in higher concentration markedly suppressed the degradation of IκB-α and phosphorylation of p38 and ERK.Conclusions CLP surgery results in the appearance of typical ALI in rats.Administration of Xuebijing can effectively inhibit the proinflammatory response in CLP rats and attenuate ALI.And such effects may be attributed to its inhibition on the proinflanunatory activation of neutrophils in lung tissue.
