Total flavonoids from astragalus complanatus attenuates lung injury following paraquat poisoning in rats through inhibiting excessive endoplasmic reticulum stress and c-Jun N-terminal kinase pathway
10.3760/cma.j.issn.2095-4352.2014.06.004
- VernacularTitle:沙苑子总黄酮通过抑制内质网应激和JNK通路过度活化减轻百草枯中毒大鼠肺损伤
- Author:
Zhijian ZHANG
;
Yaoyao DONG
;
Xiaoping LI
;
Libo PENG
- Publication Type:Journal Article
- Keywords:
Paraquat poisoning;
Lung injury;
Total flavonoids from astragalus complanatus;
c-Jun N-terminal kinase;
Endoplasmic reticulum stress;
Glucose regulated protein 78
- From:Chinese Critical Care Medicine
2014;26(6):383-387
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of total flavonoids from astragalus complanatus (FAC) on attenuating lung injury resulted from paraquat (PQ) poisoning by inhibiting excessive endoplasmic reticulum stress (ERS) and c-Jun N-terminal kinase (JNK) pathway in rat.Methods Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups (n=8 in each group),including control group,model group,dimethyl sulfoxide (DMSO) vehicle control group,and FAC in low,medium,and high dosage groups.The model was reproduced by giving PQ 80 mg/kg orally to induce lung injury.The rats in control group were treated with saline by gavage.The rats in DMSO group were given 10％ DMSO 20 mL/kg by gavage 2 hours before intraperitoneal injection of PQ,and those in FAC low,medium and high dosage groups received 40,80,160 mg·kg-1· d-1 of FAC solution intraperitoneally after the PQ administration.The rats were sacrificed 72 hours after giving PQ,and the left lung tissue was harvested 72 hours after the reproduction of experimental model.The ratio of wet/dry weight (W/D) and total lung water content (TLW) were determined.The pathohistological changes of the left lung was observed under light microscope,and scored with alveolar damage index of quantitative assessment (IQA).The mRNA expressions of JNK and glucose regulated protein 78 (GRP78) were determined by reverse transcription-polymerase chain reaction (RT-PCR),and the protein expression of JNK,phosphorylation-JNK (p-JNK),and GRP78 were determined by Western Blot.Results Compared with control group,the W/D ratio,TLW and IQA were increased significantly in model group and DMSO group,and the mRNA expressions of JNK and GRP78 and the protein expressions of JNK,p-JNK and GRP78 were markedly increased.Compared with the model group,the W/D ratio,TLW and IQA,and the expressions of JNK mRNA and p-JNK protein were significantly decreased in the FAC groups,especially in FAC high dosage group [W/D ratio:3.0 ± 0.3 vs.5.5 ± 0.5,TLW:2.2 ± 0.3 vs.4.7 ± 0.4,IQA:(15.4 ± 3.0)％ vs.(40.0 ± 5.7)％,JNK mRNA:0.21 ± 0.08 vs.0.82 ±0.27,p-JNK protein:0.31 ±0.09 vs.0.78 ±0.25,all P＜0.O1].The mRNA expression of GRP78 and the protein expressions of JNK and GRP78 were highly expressed in FAC low,medium and high dosage groups,and there was no significant difference compared with those in model group (GRP78 mRNA:0.54 ± 0.18 vs.0.74 ± 0.20,JNK protein:0.76 ± 0.27 vs.0.80 ± 0.28,GRP78 protein:0.51 ± 0.18 vs.0.69 ± 0.21,all P＞0.05).Conclusions PQ induces excessive ERS in the lung tissue resulting in lung injury.FAC has a protective effect on lung against PQ injury,and it may be related with inhibition JNK pathway in ERS.
