Ge Yun, Sun Wei, Wu Zong-Sheng, Jiang Xiao-Zhen, Qiu Qiao-Meng, Hong Guang-Liang, Liang Huan, Li Meng-Fang, Lu Zhong-Qiu
Emergency Department, First Affiliated Hospital of Wen Zhou Medical College, Wenzhou, Zhejiang Province 325000, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2012 Jan;30(1):27-32.
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).
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.
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).
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.
探讨急性硫化氢（H₂S）中毒大鼠肺组织氧化应激及核因子E2相关因子2（Nrf2）表达的动态变化及乌司他丁（UTI）的干预作用。
将96只清洁级SD大鼠随机分为四组：正常对照组（n = 8）、UTI对照组（n = 8）、H₂S中毒模型组（n = 40）和UTI治疗组（n = 40）。H₂S中毒模型组和UTI治疗组经吸入H₂S（283.515 mg/m³）1 h，然后UTI治疗组腹腔注射10⁵ U/kg的UTI 2 h。分别于染毒后2、6、12、24和48 h处死H₂S中毒模型组和UTI治疗组大鼠。检测大鼠肺组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）和谷胱甘肽（GSH）水平。检测大鼠肺组织中Nrf2 mRNA表达水平。光镜下观察大鼠肺组织病理变化并评估肺损伤评分。
与对照组比较，H₂S中毒模型组染毒后2、6和12 h肺组织SOD、CAT和GSH水平及染毒后2、6、12和24 h肺组织GSH-Px水平显著降低（P < 0.05或P < 0.01）。H₂S中毒模型组染毒后2、6、12和24 h肺组织MDA水平显著高于正常对照组（P < 0.01）。与H₂S中毒模型组比较，UTI治疗组染毒后6和12 h肺组织GSH-Px活性、染毒后2、6和12 h肺组织CAT活性、染毒后2、6、12和24 h肺组织GSH水平及染毒后2、6、12、24和48 h肺组织SOD活性显著升高（P < 0.05或P < 0.01），UTI治疗组染毒后2、6和12 h肺组织MDA水平显著降低（P < 0.01）。H₂S中毒模型组染毒后2、6、12和24 h Nrf2 mRNA表达水平分别为0.314±0.011、0.269±0.010、0.246±0.011和0.221±0.018，显著高于对照组（0.149±0.012）（P < 0.01）。与H₂S中毒模型组比较，UTI治疗组染毒后2、6、12、24和48 h Nrf2 mRNA表达水平（0.383±0.017、0.377±0.014、0.425±0.017、0.407±0.011和0.381±0.010）显著升高（P < 0.01）。H₂S中毒模型组染毒后24 h肺损伤高于UTI治疗组。组织病理学检查显示，UTI治疗组染毒后12、24和48 h肺损伤评分显著低于H₂S中毒模型组（P < 0.01）。
氧化应激和Nrf2激活可能是H₂S中毒致大鼠肺损伤的重要因素，UTI可能通过抑制ROS、改善氧化还原失衡及上调Nrf2 mRNA表达减轻大鼠肺损伤，保护大鼠肺组织免受H₂S损伤。
