RIP3介导的程序性坏死通路在LPS诱导的小鼠急性肺损伤模型中的作用

目的研究受体相互作用蛋白(RIP3)介导的程序性坏死通路在脂多糖(LPS)诱导的小鼠急性肺损伤模型(ALI)中的作用。方法将野生小鼠和RIP3敲除小鼠各30只分为四组:(a)Control RIP3-KO,(b)LPS RIP3-KO,(c)Control RIP3-WT,(d)LPS RIP3-WT。每组各15只,脂多糖组(LPS组)经小鼠气管套管滴入30mg/kg LPS,对照组经气管套管滴入等体积磷酸盐缓冲液(PBS),然后观察比较四组小鼠肺部病理损伤,小鼠直肠温度和生存率,并检测小鼠肺组织冰冻切片中坏死细胞计数和肺泡灌洗液中高迁移率族蛋白B1(HMGB1)水平。结果 RIP3敲除后,小鼠肺部病理损伤减轻,低体温症状得到明显改善,且死亡率降低。冰冻切片显示的肺组织坏死细胞计数减少,且支气管肺泡灌洗液中HMGB1表达水平也降低。结论 RIP3敲除能一定程度保护小鼠免受LPS诱导的急性肺损伤,并能减少肺组织细胞坏死的发生。

The role of RIP3-mediated necroptosis pathway in LPS-induced acute lung injury in mice

Objective To study the role of RIP3 mediated necroptosis pathway in LPS-induced acute lung injury and its mechanism.Methods 30 wild-type mice and 30 RIP3 knockout mice were divided into four groups:(a)control RIP3-KO,(b)LPS RIP3-KO,(c)control RIP3-WT and (d)LPS RIP3-WT.Each group had 15 mice.The lipopolysaccharide groups were instilled 30mg/kg LPS into the lung of mice through trachea tube,and the control groups were instilled equivalent volume of phosphate buffer solution,then the four groups were compared on pulmonary pathological changes,rectal temperature,survival rate,necrotic cell counts in frozen lung sections and HMGB1 levels in bronchoalveolar lavage fluid.Results RIP3 knockout mice had alleviated pulmonary pathological changes,hypothermia symptom,and improved survival rate.Frozen sections from RIP3 knockout mice displayed less necrotic cell counts,and reduced HMGB1 levels in BALF.Conclusion RIP3 knockout could protect mice from LPS-induced acute lung injury to some extent,and it could decrease necrosis occur in lung tissue.