Study on the mechanism of total flavonoids of selaginella tamariscina vulgaris reducing mechanical ventilation related lung injury by regulating Nrf2/HO1 signal pathway
Study on the mechanism of total flavonoids of selaginella tamariscina vulgaris reducing mechanical ventilation related lung injury by regulating Nrf2/HO1 signal pathway
Objective To investigate the effect of total flavonoids of selaginella officinalis(TFST)regulating the Nrf2/HO-1 signaling pathway on mechanical ventilation associated lung injury(VALI).Methods Forty healthy SPF grade male SD rats were selected and randomly divided into four groups(10 in each group)using a random number table method.The control group only received intubation without mechanical ventilation;In the model group,a rat VALI model was prepared using tidal volume of 30 mL/kg,ventilation frequency of 60 times/min,oxygen uptake concentration of 21％ FiO2,inhalation to exhalation ratio of 1∶2,and ventilation time of 4 hours;TFST group,starting from 2 weeks before modeling,was orally administered 800 mg/kg of total flavonoids suspension of selaginella officinalis once a day;ML385 group,pre protected with total flavonoids of selaginella vulgaris for 2 weeks,and ML385(Nrf2 inhibitor)30mg/kg was injected into the intraperitoneal cavity of rats 1 hour before mechanical ventilation.After the end of the experi-ment,the rats were euthanized and their bronchoalveolar lavage fluid(BALF)was collected for the determination of IL-6 and TNF-α using ELISA concentration.And collect rat lung tissue for HE staining to observe its pathological changes,and then score lung injury.Compared the wet to dry weight ratio(W/D)of lung tissue in each group of rats,detected the level of malondialdehyde(MDA)in lung tissue,measured the level of superoxide dismutase(SOD)in lung tissue u-sing WST-8 method,and detected the levels of Nrf2 and HO-1 protein in lung tissue using Western blot method.Results Compared with the control group,the W/D value and MDA content of lung tissue,lung injury score,and IL-6 and TNF-α in BALF in the model group were elevated.SOD content,Nrf2 and HO-1 protein levels in lung tissue decreased(P＜0.05).Compared with the model group,the W/D value and MDA content of lung tissue in the TFST group decreased,lung injury decreased,and IL-6 and TNF-α in BALF decreased decreased.SOD content,Nrf2,HO-1 protein levels in-creased(P＜0.05).The ML385 group had more severe lung injury compared to the TFST group,with W/D values and MDA content in lung tissue,as well as IL-6 and TNF-α in BALF elevated,SOD content and Nrf2 and HO-1 protein lev-els decreased(P＜0.05).Conclusion The total flavonoids of selaginella can improve mechanical ventilation related lung injury in rats by regulating the Nrf2/HO-1 pathway and activating antioxidant pathways.
关键词
机械通气/肺损伤/卷柏总黄酮/HO-1/Nrf2/氧化应激
Key words
Mechanical ventilation/Lung injury/Total flavonoids of selaginella tamariscina/HO-1/Nrf2/Oxida-tive stress
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