The protective effect of oridonin on hyperoxia-indused lung injure

Abstract

Objective To investigate the protective effect of oridonin on hyperoxia-induced lung injury (HALI). Methods A total of 46 SD rats were randomly divided into control group (n=7), HALI group (n=13), Nec-1 (necroptosis inhibitor) group (n=13), and oridonin group (n=13). Rats were exposed to pure oxygen for 6 h at 0.25 MPa to induce HALI. Then the rats were intraperitoneally injected with 1 mg/kg Nec-1 or 10 mg/kg Oridonin, 30 min before hyperoxia exposure. Rats were sacrificed at 24 or 48 h after the end of hyperoxia exposure. Lung injury was assessed by histological examination, lung wet-to-dry ratio (W/D), bronchoalveolar lavage fluid (BALF) examinations, assessments of oxidative stress and inflammatory factors in the lung; lung tissues were also collected for the detection of RIP1, RIP3, and MLKL protein expressions by Western blotting and evaluation of the interaction between RIP1 and RIP3. Results As compared with the control group, hyperoxia exposure resulted in significant lung injury and increase in the number of necroptosis positive cells, which were accompanied by the elevated expressions of RIP1, RIP3 and MLKL in the lung. As compared with the HILI group, intraperitoneal injection of oridonin could improve lung injury to a certain extent, inhibit oxidative stress and inflammatory factors, reduce the necroptosis positive cells [HALI group: 64.7±6.5 (RIP1), 46.3±5.4 (RIP3); Nec-1 group: 39.4±4.8, 26.6±4.0; Oridonin group: 36.9±5.4, 27.1±3.9], decrease the expressions of RIP1, RIP3, and MLKL, and down-regulate the interaction between RIP1 and RIP3. Conclusion This study indicates that the lung protective effect of oridonin on HALI may be related to its inhibitory effect on necroptosis in the lung. Key words: Hyperoxia induced lung injury; Necroptosis; Oridonin; Lung protection; Rat