关键词: 次氯酸钠, 肺损伤, 细胞凋亡, 氧化应激, 炎症, 自噬

Abstract: OBJECTIVE：To use a mouse lung injury model to investigated toxicity of inhaled NaClO disinfectant. METHODS：Mice were exposed by inhalation to 100 mmol/L NaClO of standard solution dissolved in 0.9% NaCl solution，with gradient dilution. Lung functions of mice were measured 24 h using a lung function instrument after infection. Blood samples d from the orbit and alveolar lavage fluid and lung tissues were collected and stained with HE. Organelles such as mitochondria in lung tissue cells were evaluated for morphology. TUNNEL staining was conducted for apoptosis. The BALF protein concentrations were measured by BCA. Cells of BALF were counted by FALCS，and analyzed using Western blot. The relative protein expression of antioxidant enzymes，apoptosis and autophagy were evaluated. The ELISA kit was used to detect inflammation-related protein content. The mRNA levels of antioxidant enzymes and inflammation were measured by qPCR. Lung tissue homogenates were analyzed for MDA content and SOD enzyme activity. RESULTS：Compared with the control group，the degrees of structural damage in the 75，150，300 μg/L NaClO infected groups were concentration dependent. The protein concentrations of 75 μg/L alveolar lavage fluid did not change significantly. The protein concentrations of the 150 and 300 μg/L NaClO infected groups increased significantly (P<0.05)，and the cell number increased significantly (P<0.05). The 150 μg/L NaClO was selected as the study concentration. Compared with the control group，pulmonary function injury was increased (P<0.05)， protein expressions of antioxidant enzymes SOD2 and Nrf2 were disturbed (P<0.05)， mRNA levels of SOD2，Nrf2，and CAT were reduced (P<0.05). The protein concentrations of IL-1β and TNF-α in serum，alveolar lavage fluid and tissue homogenate were increased (P<0.05)，with higher relative mRNA expression in the tissue homogenate (P<0.05)，and a marked increase in the number of apoptotic cells. There was increased expression of Bax and cleaved caspase-3 proteins (P<0.05). Lung tissue cell mitochondria were significantly swollen，with the presence of autollysosomes，Beclin1， increased protein expression (P<0.05)，and proprotein expression of P62 (P<0.01). CONCLUSION：A NaClO-induced mouse lung injury model was established which showed that NaClO could induce apoptosis，oxidative stress，inflammation and autophagy in mice.

Key words: sodium hypochlorite, lung injury, apoptosis, oxidative stress, inflammation, autophagy