Empirical study of protcetive effect of olmesartan on acute lung injury induced by paraquat in rats / 中华急诊医学杂志

ABSTRACT

Objective To explore the therapeutic effect of olmesartan (OLM) on acute lung injury induced by paraquat (PQ) in rats in order to study its action mechanism.Methods A total of 70 Wister rats wererandomly (random number) divided into 5 groups,namely control group (C group,n =10),poisoning group (PQ group,n =15),rats treated by OLM with low dose (LD group,n =15),moderate dose (MD group,n=15) and high dose (HD group,n =15).PQ (80 mg/kg) was administered by gavage route in PQ group and in OLM groups for paraquat poisoning modelling,while in C group,equivalent normal saline was given instead.The OLM was administered by gastric instillation in OLM treatment groups (LD group5 mg/kg; MD group10 ng/kg; HD group15 mg/kg) 6 hours after paraquat gavage and once a day for 7 days,while in C group and PQ group,normal saline was used instead.All rats were sacrificed 12 hours after the last dose treatment.The levels of glutathione peroxidase (GSH-Px,energy units),superoxide dismutase (SOD,U/mg pro),malondialdehyde (MDA,nmol/mg pro) in lung tissue,and the levels of serum transforming growth factor beta-1 (TGF-β1,pg/mL) and pH,oxygen partial pressure (PaO2) and bicarbonate ions concentration (HCO3-) were determined.Further,the lung coefficient and lung fibrous tissue hyperplasia grading were calculated.Correlation analysis was carried out to explore the correlation among GSH-Px,SOD,MDA,lung coefficient,lung hyperplasia of fibrous tissue and TGF-β1.The lung tissue were prepared for microscopy observation after Hematoxylin-eosin staining method (HE staining) as well.The difference between groups was compared by one-way analysis of variance,and correlation analysis carried out by using Pearson and Spearman rank correlation coefficient.Results The levels of GSH-Px and SOD in lung tissue of PQ and OLM treatment groups were significantly lower than those in C group,while in OLM treatment groups,those were higher than those of PQ group,and the HD group showed most obvious (all P ＜ 0.05).The level of MDA in lung tissue in PQ and OLM treatment groups were significantly highcr than that in C group while in OLM treatment groups,that was lower than that in PQ group,and the HD group showed most obvious (all P ＜ 0.05),and there were no differences between the LD group and MD group (all P ＞ 0.05).The lung coefficient and lung fibrous tissue hyperplasia grading in PQ and OLM treatment groups were significantly higher than those in C group,while in OLM treatment groups,those were lower than those in PQ group,and the HD group showed most obvious (all P ＜ 0.05).The level of serum TGF-β1 in PQ and OLM treatment groups were significantly higher than that inC group,while in OLM treatment groups,that was lower than that in PQ group,and the HD group showed most evident (all P ＜ 0.05),and there were no differences between the LD group and MD group (all P ＞0.05).The pH,PaO2 and HCO3-in PQ and OLM treatment groups were significantly lower than those in C group,while difference between LD and HD groups was also statistical significance (all P ＜ 0.05),while there were no differences between the PQ group and LD group as well as the LD group and MD group (all P ＞ 0.05).The correlation analysis showed GSH-Px and SOD had negative correlation with TGF-β1 [the correlation coefficient (r) were respectively-0.860 and-0.856,all P＜0.05],while MDA,lung coefficient and lung fibrous tissue hyperplasia grading had positive correlation with TGF-β1 (r were respectively 0.800,0.830 and 0.656,all P ＜ 0.05).Lung tissue section showed the degree of alveolar septa widened,alveolar collapse and inflammatory cells infiltration in OLM treatment groups were milder than those in PQ group,and the mildest in HD group.Conclusions OLM can attenuate the pulmonary edema and pulmonary fibrosis caused by paraquat poisoning and maybe it is associated with reducing the expression of TGF-β1 and inhibiting oxidative stress reaction.