Effect of ulinastatin on oxidative stress and nuclear factor E2-related factor 2 expression in the lung tissues of acute hydrogen sulfide intoxicated rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes of oxidative stress and nuclear factor-E2 related factor 2 (Nrf2) expression in the lung tissues of acute hydrogen sulfide (H2S) intoxicated rats and intervention effects of ulinastatin (UTI).</p><p><b>METHODS</b>A total of 96 SD rats of clean grade were divided randomly into four groups: normal control group (n = 8), UTI control group (n = 8), H2S -intoxicated model group (n = 40), and UTI treatment group (n = 40). The H2S-intoxicated model group and UTI treatment group were exposed to H2S (283.515 mg/m3) by inhalation for 1h, then UTI treatment group was intraperitoneally exposed to UTI at the dose of 10(5) U/kg for 2 h. H2S-intoxicated model group and UTI treatment group were sacrificed at 2, 6, 12, 24 and 48 h after exposure, respectively. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH) in the rat lung tissues were measured. The expression levels of Nrf2 mRNA in the rat lung tissues were detected. Pathological changes of rat lung tissues were observed under a light microscope and the lung injury scores were evaluated.</p><p><b>RESULTS</b>Compared with control group, the pulmonary SOD, CAT and GSH levels at 2,6 and 12 h after exposure and the pulmonary GSH-Px levels at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group significantly decreased (P < 0.05 or P < 0.01). The levels of pulmonary MDA at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group were significantly higher than those in normal control group (P < 0.01). As compared with H2S -intoxicated model group, the pulmonary GSH-Px activities at 6 and 12 h after exposure, the pulmonary CAT activities at 2, 6 and 12 h after exposure, the pulmonary GSH levels at 2, 6, 12 and 24 h after exposure and the pulmonary SOD activities at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.05 or P < 0.01), the pulmonary MDA levels at 2, 6 and 12 h after exposure in UTI treatment group significantly decreased (P < 0.01). The expression levels of Nrf2 mRNA at 2, 6, 12, 24 h after exposure in H2S-intoxicated model group were 0.314 +/- 0.011, 0.269 +/- 0.010, 0.246 +/- 0.011 and 0.221 +/- 0.018, respectively, which were significantly higher than those (0.149 +/- 0.012) in control group (P < 0.01). As compared with H2S-intoxicated model group, the expression levels (0.383 +/- 0.017, 0.377 +/- 0.014, 0.425 +/- 0.017, 0.407 +/- 0.011 and 0.381 +/- 0.010) of Nrf2 mRNA at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.01). The lung injury at 24 h after exposure in H2S-intoxicated model group was higher than that in UTI treatment group. Histopathological examination showed that the scores of lung injury at 12, 24 and 48 h after exposure in UTI treatment group was significantly lower than those in H2S-intoxicated model group (P < 0.01).</p><p><b>CONCLUSION</b>Oxidative stress and Nrf2 activation may be the important factors in rat lung injury induced by H2S-intoxicated, UTI may reduce the rat lung injury and protect the rat lung from damage induced by H2S by inhibiting ROS, improving the imbalance in redox and up-regulating Nrf2 mRNA expression.</p>

The effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat (PQ).</p><p><b>METHODS</b>After A549 cells transfected with Ad-RUNrf2 were treated by RU486 at the doses of 10(-10), 10(-9), 10(-8) and 10(-7) mol/L for 6 h, A549 cell cultures were exposed to 10(-3) mol/L of PQ for 48 h. Then qRT-PCR and EMSA assays were used to detect the expression of Nrf2 gene, and qRT-PCR and ELISA assays were utilized to measure the effects of Nrf2 gene on the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α, apoptotic factors Caspase-3, Caspase-9 and Cytochrome C. The oxidation factors (CAT and MDA protein contents) were observed by Chemical Colorimetric Analysis.</p><p><b>RESULTS</b>Nrf2 gene relative expression and protein contents increased with RU486 concentrations, and the above expression was the highest when the concentration of RU486 was 10(-7) mol/L, which was significantly higher than those in control and PQ exposure groups (P < 0.01 or P < 0.05). The relative gene expression and protein expression of IL-6 and TNF-α enhanced with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05), while the change of IL-10 content was the opposite. The relative expression of Caspase3, Caspase9 and Cytochrome C genes also increased with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05). The content of CAT enhanced with RU486 concentration, which was the highest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.05). But the change of MDA content was the contrary.</p><p><b>CONCLUSION</b>Nrf2 expression induced by RU486 can promote the balance of oxidation-antioxidation system in A549 cells and inhibit the inflammation and apoptosis factors, which has a protective effect on A549 cell injury induced by PQ.</p>