Emodin ameliorates severe acute pancreatitis-associated lung injury by inhibiting the ATF6/CHOP pathway in alveolar macrophages / 免疫学杂志

ABSTRACT

This study was designed to investigate the effect of emodin(EMO)on endoplasmic reticulum stress(ERS)in alveolar macrophages(AMs)of rats with severe acute pancreatitis(SAP)and the underlying mechanism.Forty rats were recruited and randomized into four groups:sham-operation(SO)group,SAP group,4-phenylbutyric acid(4-PBA)group and EMO group.The SAP model was established by retrograde injection of 5%sodium taurocholate into the biliopancreatic duct.HE staining was performed to observe the pathological changes in the pancreas and lung;the wet/dry weight ratio of lung tissue was calculated.Arterial partial pressure of the oxygen(PaO2)and carbon dioxide(PaCO2)were measured;the serum amylase activity and the levels of inflammatory factors TNF-α and IL-6 were evaluated.TUNEL staining was used to determine the cell apoptosis rate of lung tissue;Western blot was used to detect the protein expression levels of GRP78,ATF6,CHOP,and Caspase-12.Moreover,rat AMs(NR8383)were signed into control(CON)group,lipopolysaccharide(LPS)group,4-phenylbutyric acid(4-PBA)group and EMO group in vitro.Glutathione(GSH)and malondialdehyde(MDA)levels in the cell medium were measured,as were the protein expression levels of GRP78,ATF6,CHOP,and Caspase-12 in AMs.For experiments in vivo,compared with the SO group,the pathological score of pancreatic and lung in SAP rats was increased(P<0.05),the levels of serum amylase activity,IL-6 and TNF-α were increased(P<0.05),the wet/dry weight ratio and apoptosis rate of lung tissue were increased(P<0.05),PaO2 was decreased,PaCO2 was increased(P<0.05),and the protein expression of GRP78,ATF6,CHOP and Caspase-12 were increased in lung tissue(P<0.05).Compared with the SAP group,these indexes mentioned above in the 4-PBA and EMO groups were reversed(P<0.05).For experiments in vitro,compared with the CON group,GSH levels were decreased,and MDA levels were increased in the cell medium of LPS group(P<0.05),and the expression of GRP78,ATF6,CHOP and Caspase-12 proteins were upregulated(P<0.05).Compared with the LPS group,these indexes mentioned above in in cell medium of the 4-PBA and EMO groups were reversed(P<0.05).In conclusion,the protective effect of EMO on pancreatic and lung injury in SAP rats may be closely related to the inhibition of ATF6/CHOP pathway-induced inflammation and oxidative stress in AMs.