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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 (PQ) poisoning; and to clear Salubrinal (Sal) effects on PERK-eIF2a-ATF4 signaling pathway and lung injury caused by paraquat. Methods: 200 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 4 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 rats were given gastric lavage with PQ solution of 40ml/kg once only and 1ml of saline by intraperitoneal injection twice daily. Group C:the rats were given Sal (0.5mg/kg) of 1ml and 1ml of saline once daily by intraperitoneal injection in the 1st,3rd,and 5th day after PQ poisoning. Group D: Sal (1.0mg/kg) treatment group, the rats were given Sal (1.0mg/kg) 1ml and 1ml saline once daily by intraperitoneal injection in the 1st,3rd,and 5th day after PQ poisoning. Then we observed the general state of 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 the expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein were detected by western blotting in lung tissue.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 that of 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 Salubrinal treatment group was more serious than that of the exposure group, the expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein was increased, with the difference statistically significant (P <0.05). The degree of inflammation and protein expression in Sal (0.5mg/kg) treatment group was between Sal (1.0mg/kg) treatment group and the exposure group, with the difference statistically significant (P <0.05). Mortality: The mortality of group B,group C and group D were 54.0%, 70.0%, 88.0%; and the mortality of Sal (1.0mg/kg) treatment group was the highest,with the difference statistically significant (P <0.05). Conclusions: Acute PQ poisoning can enhance ERS, PERK-eIF2a-ATF4 signaling pathway and cause lung injury; Salubrinal can strengthen ERS, increase PERK-eIF2a-ATF4 signal transduction pathway and aggravate acute lung injury caused by PQ poisoning.