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Abstract

Introduction: In this study,we aim to investigate the changes of PERK-eIF2a-ATF4 signaling pathway in endoplasmic reticulum stress after acute paraquat poisoning and to clear ulinastatin’s (UTI) effects on PERK-eIF2a-ATF4 signaling pathway and lung injury caused by paraquat. Methods: 150 Wistar rats were chosen from Experimental Animal Center of Jilin University, weighted 250 +10g each, half male and half female.These rats were randomly divided into 3 groups, 50 rats in each group.Group A: control group, the rats were given gastric lavage with 1 ml of normal saline once only and 1ml of saline by intraperitoneal injection twice daily. Group B: poisoned-nontreated group: the rat were given gastric lavage with PQ solution of 40ml/kg once only and 1ml of saline by intraperitoneal injection twice daily. Group C: UTI treatment group, the rats were given UTI (120,000 IU/ kg) twice daily by intraperitoneal injection after PQ poisoning. Then we observed the general state of the rats, and in the 7th day after poisoning, the lungs were taken and the lung tissue morphology were obererved by HE staining, the expression of PERK,P-elF2a,ATF4 were detected by immunohistochemistry,and GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein were detected by western blotting. Then we did statistical analysis. Results: In the 7th day of acute PQ poisoning, HE staining of lung tissue exposed that there was a lot of inflammatory exudation in group B; the expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein were higher than those in the control group, with the difference statistically significant (P <0.05). There was basal expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP in the control group. The inflammatory response in UTI treatment group was slighter than that in the exposure group, and the expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein was decreased or there was no expression, with the difference statistically significant (P <0.05). Mortality: the rats of UTI treatment group and control group were all survived,but the mortality rate of exposure group was 54.0%, with the difference statistically significant (P <0.05). Conclusions: Acute PQ poisoning can enhance ERS, PERK-eIF2a-ATF4 signaling pathway and cause lung injury; UTI can suppress ERS,decrease PERK-eIF2a-ATF4 signal transduction pathway and mitigate acute lung injury caused by PQ poisoning.