| Objective To investigate PERK-eIF2a-ATF4signaling pathway changes inERS of acute PQ poisoning；to investigate effects of UTI and/or Sal onPERK-eIF2a-ATF4signaling pathway and its role in lung injury.Methods All of the350wistar rats are provided by the ExperimentalAnimal Center of Jilin University. The body weight of the rats is (250+10) g,including half male and half female. The rats are divided into seven groupsrandomly.There were50rats in each group. Group A is the normal control group,using1ml normal saline by one time intragastric administration, using1ml ofnormal saline by intraperitoneal injection twice a day. Group B is PQ exposedgroup, using PQ solution40mg/kg one time intragastric administration, using1ml of normal saline by intraperitoneal injection twice a day. Group C is UTItreatment group, using UTI (12000IU/kg) by intraperitoneal injection twice aday after PQ poisoning. Group D is Sal (0.5mg/kg) treatment group, using1ml ofSal (0.5mg/kg) by intraperitoneal injection in1st,3rd,5th day after PQ poisoning,and using1ml of normal saline by intraperitoneal injection once a day. Group F isUTI+Sal (0.5mg/kg) treatment group, using UTI (12000IU/kg) byintraperitoneal injection twice a day after PQ poisoning and using1ml of Sal(0.5mg/kg) by intraperitoneal injection in1st,3rd,5th day after PQ poisoning. Sal and UTI were injected at the same time in order to ensure intraperitonealinjection twice a day.(Note: Sal and UTI were injected at the same time, eachvolume of0.5ml,total volume of1ml). Group G is UTI+Sal (1.0mg/kg)treatment group,using UTI (12000IU/kg) by intraperitoneal injection twice aday,using1ml of Sal (1.0mg/kg) by intraperitoneal injection in1st,3rd,5th dayafter PQ poisoning in rats, and using Sal (1.0mg/kg) by intraperitoneal injectiononce a day. The method of administration is the same as group F. The generalstatus of the rats were observed; their lungs were extracted on the7th day afterpoisoning. We observed lung tissue morphology by HE staining, observed PERK,P-elF2a, ATF4expression of lung tissue by immunohistochemistry and observedGRP78, PDI, PERK, P-elF2a, ATF4and CHOP protein expression by Westernblotting.Then，we use statistical analysis.Result①In the7thday after PQ poisoning, HE staining shows a largenumber of inflammatory cells leaking in the lung tissue of PQ poisoninggroup.The protein expression of GRP78, PDI, PERK, P-elF2a, ATF4and CHOPare higher than those of the control group, and the differences are statisticallysignificant (P <0.05).②There is basic expression of GRP78, PDI, PERK,P-elF2a, ATF4and CHOP in the control group.③The inflammatory response islighter in UTI treatment group.The protein expressions of GRP78PDI, PERK,P-elF2a, ATF4and CHOP are less or no expression in UTI treatment group.Thedifferences are statistically significant (P <0.05).④The inflammatory responsemore serious. The protein expressions of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP in Sal (1.0mg/kg) treatment group are more. The differences arestatistically significant (P <0.05).⑤The inflammatory response and the proteinexpressions in Sal (0.5mg/kg) treatment group and Sal ((0.5mg/kg,1.0mg/kg) incombination with UTI treatment group are between Sal (1.0mg/kg) treatmentgroup and UTI treatment group. The differences are statistically significant (P<0.05).⑥Mortality: the rats in the control group and the the UTI treatmentgroup were all survived, with a general state. The rat mortality in PQ exposedgroup, Sal (0.5mg/kg) treatment group, Sal (1.0mg/kg) treatment group, UTI+Sal (0.5mg/kg) treatment group, UTI+Sal (1.0mg/kg) treatment group were54.0%,70.0%,88.0%,58.0%,60.0%, and the Sal (1.0mg/kg) treatment group hasthe highest fatality rate, with the differences are statistically significant (P <0.05);while in the other four groups, the difference of mortality was not statisticallysignificant (P>0.05).Conclusion①Acute PQ poisoning can increase PERK-eIF2a-ATF4signaltransduction pathway in ERS, with the result of acute lung injury;②UTI cansuppress the ERS and decrease protein expression in PERK-eIF2a-ATF4signaltransduction pathway, which can reduce acute PQ poisoning lung injury;③Salcan enhance ERS and increase protein expression in PERK-eIF2a-ATF4signaltransdu-ction pathway,which can increase acute PQ poisoning lung injury. |
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