The effect of penehyclidine hydrochloride on pulmonary interstitial fibrosis induced by paraquat in rats

Abstract

Objective To investigate the effect of penehyclidine hydrochloride(PHC) on pulmonary interstitial fibrosis(PIF) induced by paraquat (PQ) in rats.Methods Forty-eight male SD rats were randomly divided into four groups,control group(Con group),model group(Mod group),PHC group and dexamethasone(Dex) group.Then every group was randomly divided into 7th day and 22th day subgroup,there were 6 rats in every group.20％ PQ (18 mg/kg,diluted to 1 ml) was injected peritoneally to make poisoning model,while in the Con group 1 ml normal saline was used.30 min after exposed to PQ,rats in PHC group and Dex group were respectively intraperitoneally injected with PHC (0.1 mg/kg) and Dex (3 mg/kg),and then repeated injection once per 24 h,all intervention drug were diluted to 1 ml with normal saline.Rats in Con group and Mod group at corresponding time points were given with equal volume of normal saline.On the 7th day and 22th day respectively,experimental animals were killed to detect the partial pressure of oxygen in artery (PaO2) and partial pressure of carbon dioxide in artery (PaCO2),the lung wet/dry ratio (W/D),the pathological changes of lung tissue by hematoxylin-eosin (HE) staining and Masson staining,and the transforming growth factor-β1 (TGF-β1) expression in lung tissue with immunohistochemistry.Results Comparing with Con group,the PaO2 was significantly lower[(79±6) mm Hg/(78±8) mm Hg vs(39±6) mm Hg/(44±5) mm Hg,(46±4) mm Hg/(52±5) mm Hg,(54±6) mm Hg/(60±6) mm Hg(1 mm Hg=0.133 kPa)],the PaCO2[(44±7) mm Hg/(45±7) mm Hg vs(92±5) mm Hg/(82±4) mm Hg,(84±8) mm Hg/(73±8) mm Hg,(75±7) mm Hg/(65±7) mm Hg],pulmonary W/D[(2.60±0.25)/(2.58±0.22) vs(5.67±0.61)/(4.57±0.39),(4.25±0.44)/(3.85±0.34),(3.69±0.40)/(3.40±0.28)] and TGF-β1[(136±7)/(140±7) vs(215±23)/(322±29),(193±11)/(246±16),(186±11)/(214±14)] expression was significantly increased in rats exposed to PQ.The morphological changes presented acute pulmonary inflammatiuon on the 7th day,while on the 22th day,PIF appeared.Penehyclidine hydrochloride and Dex,could significantly increase PaO2,decrease PaCO2.Inhibit lung inflammation infiltration,reduce PIF,significantly reduce lung W/D and TGF-β1 expression in the lung tissue,and there were no obvious difference in PHC group and Dex group.Conclusions PHC can inhibitting the expression of TGF-31,then reduce lung inflammation infiltration and suppress the occurrence of PIF of PQ poisoning in rats. Key words: Penehyclidine hydrochloride; Pulmonary interstitial fibrosis; Paraquat; Transforming growth factor-β1