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Objective To investigate the effects of cathepsin B (CTSB) down-regulation on pyroptosis of lung tissue in mice with sepsis-induced acute lung injury. Methods Thirty SPF healthy male C57BL/6 mice were randomly divided into three groups: sham group (n=6), sepsis group (n=15), and sepsis plus CTSB inhibitor CA-074 group (sepsis+CA-074 group, n=9).Sepsis was induced by cecal ligation and puncture (CLP). Except for cecal ligation and perforation, other operations in the sham group were the same as those in sepsis group. 10 mg/kg CA-074 was intraperitoneally injected in sepsis+CA-074 group at 15 min after CLP. The mice were sacrificed 24 h after CLP. Bronchoalveolar lavage fluid (BALF) was collected for measurement of the white blood cell count and IL-18 and IL-1β concentrations with ELISA. Lung tissues were obtained for the determination of lung injury score, wet/dry lung weight ratio, the expressions of caveolin-1, MCPIP1, CTSB, caspase-1, and GSDMD mRNA (by RT-PCR), as well as the protein expressions of CTSB, caspase-1, and GSDMD (by Western blotting). Results The mice in sham group were normal throughout the observation period, and the 24 h survival rate after the operation was 100.0%. The sepsis mice showed obvious symptoms such as piloerection, dilatory, anorexia, and apathy, and these symptoms were improved in sepsis+CA-074 group.The 24 h survival rate after surgery in the two groups was 40.0% and 66.7%, respectively. Compared with sham group, the count of leukocytes and the expression of IL-18 and IL-1β in BALF were significantly increased, the wet/dry lung weight ratio and lung injury score were increased, the expression of caveolin-1 mRNA was up-regulated, the expression of MCPIP1 mRNA was down-regulated, and the expressions of CTSB, caspase-1, and GSDMD were up-regulated in the sepsis group (P<0.05). Compared with sepsis group, the count of leukocytes and the expressions of inflammatory factors were decreased, the wet/dry lung weight ratio and lung injury score were decreased, the expression of caveolin-1 mRNA was down-regulated, the expression of MCPIP1 mRNA was up-regulated, proteins associated with pyroptosis were significantly decreased, and the protein expression of CTSB was decreased in sepsis+CA-074 group (P<0.05). However, there was no significant change in the parameter of CTSB mRNA between the sepsis and sepsis+CA-074 groups (P=0.973). Conclusion Increased CTSB expression occurs in lung tissue with sepsis-induced acute lung injury, and inhibition of CTSB may alleviate sepsis-induced acute lung injury by suppressing pyroptosis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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