Ming-Li Sun

Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning.

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had disappeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraquat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

The effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat poisoning

OBJECTIVE To investigate the effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat (PQ) poisoning, and to explore its mechanism. METHODS 200 Wistar rats were randomly divided into four groups by randomized arrangement table formed by computer, with 50 rats in each group. PQ poisoning model was reproduced by one time gastric lavage with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline (NS) once a day. The rats in control group were lavaged once with 1 mL of NS followed by intraperitoneal injection of 1 mL NS twice a day. The rats in Sal 0.5 and Sal 1.0 groups were intraperitoneal injected with 1 mL Salubrinal 0.5 mg/kg or 1.0 mg/kg on the 1st, 3rd, and 5th day after PQ poisoning once a day. The lung tissue was harvested on the 7th day after poisoning, and the changes in histomorphology were observed using hematoxylin and eosin (HE) staining. The positive expression of autophagy-related protein LC3-II in lung tissue was observed after immunohistochemistry staining, and LC3-II and caspase-3 protein expressions were determined by Western Blot. RESULTS HE staining results showed partial abnormal pulmonary structure in the PQ poisoning group: collapse of pulmonary alveoli, enlargement of the cavity, local infiltration of inflammatory cells, increasing thickness in the alveoli wall and obvious bleeding in the local lung tissue. Compared with the PQ poisoning group, the above changes in Sal 0.5 and Sal 1.0 groups were obviously relieved. It was shown by immunohistochemistry staining that compared with control group, the positive expression of LC3-II was obviously decreased in the PQ poisoning group, Sal 0.5, and Sal 1.0 groups (A value: 78.34 ± 10.71, 76.52 ± 8.21, 77.48 ± 9.11 vs. 117.58 ± 15.26, all P<0.05). There was no significant difference in positive expression of LC3-II between each of the later three groups (all P>0.05). Western Blot results showed: compared with the control group, the protein expressions of LC3-II and caspase-3 were significantly increased in PQ poisoning group [LC3-II (A value): 0.22 ± 0.05 vs. 0.14 ± 0.03, caspase-3 (A value): 0.115 ± 0.013 vs. 0.023 ± 0.006, both P<0.05]. Compared with PQ poisoning group, the protein expressions of LC3-II and caspase-3 were obviously decreased in the Sal 0.5 and Sal 1.0 groups [LC3-II (A value): 0.19 ± 0.05, 0.18 ± 0.04 vs. 0.22 ± 0.05; caspase-3(A value): 0.078 ± 0.012, 0.076 ± 0.010 vs. 0.115 ± 0.013, all P<0.05]. CONCLUSIONS The endoplasmic reticulum stress-autophagy is activated in the pulmonary cell of acute PQ poisoning rats. Salubrinal can decrease the autophagy and apoptosis in the lung of rats with acute PQ poisoning, which play a role in the treatment.

204: THE EFFECTS ON PERK-EIF2A-ATF4 PATHWAY CHANGES AND ACUTE LUNG INJURY OF PARQUET RATS BY SALUBRINAL

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