Abstract: Objective To investigate the effect of neutralizing antibody of high mobility groupprotein 1 (HMGB1) on lung injury in systemic lupus erythematosus (SLE) mice and the underlying mechanism. Methods Thirty MRL / lpr mice were randomly divided into 3 groups: MRL / lprgroup, MRL / lpr + anti-HMGB1 group and MRL / lpr + MCC950 group, with 10 mice in each group, and another 10 wild-type C57BL / 6 mice were taken as the control group. Mice in each group were administered for 4 weeks. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the lung histopathological changes and collagen fiber deposition in each group. The levels of interleukin-1β ( IL-1β), IL-6, IL-18 and tumor necrosis factor-α ( TNF-α) in alveolar lavage fluid of mice in each group were detected by enzyme-linked immunosorbent assay ( ELISA). The fluorescence expression of nucleotide-binding oligomerized domain-like receptor protein 3 (NLRP3) in lung tissues of mice in each group was observed by immunofluorescence staining. The expression levels of HMGB1 and NLRP3, apoptosis-related spect-like protein containing a CARD (ASC) protein, Caspase-1, gasdermin D ( GSDMD) in mice lung tissues were detected by Western blotting. Results The lung tissues in the MRL / lpr group showed serious pathological injury symptoms,the collagen fiber deposition area was significantly increased (P< 0. 05), and the levels of IL-1β,IL-6, IL-18 and TNF-α in alveolar lavage fluid were significantly increased, when compared withthose in the control group (P < 0. 05). In addition, the mean fluorescence intensity of NLRP3 in lung tissues in the MRL / lpr group was significantly increased (P< 0. 05), and the relative proteinexpression levels of HMGB1 and NLRP3, ASC, Caspase-1, GSDMD were significantly up-regulated when compared with those in the control group (P< 0. 05). The lung tissue injuries in the MRL /lpr + anti-HMGB1 group and the MRL / lpr + MCC950 group were significantly improved, and the collagen fiber deposition area was significantly reduced, when compared with those in the MRL / lprgroup (P< 0. 05). In addition, the levels of IL-1β, IL-6, IL-18 and TNF-α in alveolar lavage fluid in the MRL / lpr + anti-HMGB1 group and the MRL / lpr + MCC950 group were significantly decreased (P< 0. 05), the mean fluorescence intensity of NLRP3 in lung tissues was significantly decreased (P < 0. 05), and the relative protein expression levels of HMGB1 and NLRP3, ASC,Caspase-1, GSDMD in lung tissues were significantly down-regulated, when compared with those inthe control group (P< 0. 05). Conclusion HMGB1 neutralizing antibody can ameliorate lung injury in mice with SLE, which may be achieved by inhibiting pyroptosis.

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