冬凌草甲素对高氧性肺损伤的保护作用

目的:探讨冬凌草甲素对高氧性肺损伤(HALI)的保护作用。方法:建立高氧性肺损伤SD大鼠模型,将46只SD大鼠随机分为对照组( n=7)、HALI组( n=13)、Nec-1(程序性坏死抑制剂)组( n=13)和冬凌草甲素组( n=13)。将大鼠在0.25 MPa下暴露于纯氧中6 h以诱导HALI。高氧暴露前30 min,大鼠腹腔内注射1 mg/kg Nec-1或10 mg/kg冬凌草甲素。高氧暴露后24 h或48 h处死动物。通过检测不同组大鼠肺的组织学、肺干湿比(W/D)、支气管肺泡灌洗液(BALF)、肺组织氧化应激及炎症因子以评估肺损伤;同时取不同组大鼠肺组织,检测RIP1、RIP3和混合系蛋白激酶结构域样蛋白(MLKL)的表达,以及RIP1和RIP3之间的相互作用。 结果:与对照组相比,高氧暴露导致明显肺损伤,增加程序性坏死细胞数量,伴随肺内RIP1、RIP3和MLKL的表达增加。与HALI组相比,高氧暴露前腹腔注射冬凌草甲素能一定程度改善肺损伤,抑制氧化应激和炎症因子,降低程序性坏死细胞数量[HALI组的RIP1和RIP3表达量分别为64.7±6.5和46.3±5.4, Nec-1组分别为39.4±4.8和26.6±4.0,冬凌草甲素组分别为36.9±5.4和27.1±3.9],伴随RIP1、RIP3和MLKL表达的下降以及RIP1和RIP3相互作用下调。结论:冬凌草甲素对HALI的保护作用可能与其抑制肺内细胞程序性坏死有关。

The protective effect of oridonin on hyperoxia-indused lung injure

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.