Role of necroptosis in hyperoxia-induced acute lung injury in preadolescent rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of necroptosis in hyperoxia-induced acute lung injury(ALI)in preadolescent rats.Methods A total of 72 clean-grade healthy male Sprague-Dawley rats,aged 14 days,weighing 40-50 g,were divided into 3 groups(n＝24 each)by using a random number table method: control group(group C),hyperoxia-induced ALI group(group ALI)and hyperoxia-induced ALI and necrostatin-1 group(group ALI+N).The rats of group ALI+N was intraperitoneally injected with ne-crostatin-1 1.0 mg/kg once a day for 3 consecutive days.The rats were intraperitoneally injected with dime-thyl sulfoxide 0.2 ml/kg once a day for 3 consecutive days in C and ALI groups.The animals were sacrificed at 72 h after inhaling oxygen,and bronchoalveolar lavage fluid(BALF)was collected for determination of interleukin-6(IL-6)and IL-8 concentrations(by enzyme-linked immunosorbent assay),superoxide dis-mutase(SOD)activity(by xanthine oxidase method),and malondialdehyde(MDA)concentration(by thiobarbituric acid method).Lung tissues were taken for measurement of wet/dry weight ratio(W/D ratio)and for examination of the pathological changes(with a light microscope)and ultrastructure of lung tissues(with an electron microscope).The injured alveolus rate(IAR)was calculated.The expression of recep-tor-interacting protein kinase 1(RIPK1),RIPK3 and mixed-lineage kinase domain-like protein(MLKL)in lung tissues was detected by Western blot.Results Compared with group C,the concentrations of IL-6,IL-8 and MDA in BALF were significantly increased,the activity of SOD in BALF was decreased,the W/D ratio and IAR of lung tissues were increased,the expression of RIPK1,RIPK3 and MLKL in lung tis-sues was up-regulated(P＜0.05),and the pathological damage was accentuated in group ALI.Compared with group ALI,the concentrations of IL-6,IL-8 and MDA in BALF were significantly deceased,the ac-tivity of SOD in BALF was increased,the W/D ratio and IAR of lung tissues were decreased,the expres-sion of RIPK1,RIPK3 and MLKL in lung tissues was down-regulated(P＜0.05),and the pathological damage was significantly attenuated in group ALI+N.Conclusion Necroptosis is involved in the patho-physiological process of hyperoxia-induced ALI in preadolescent rats.