Biochemical and biophysical research communications · 2025
Propofol lessens renal ischemia/reperfusion-acute lung injury by preventing mTOR-induced Pyroptosis.
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Liu Siyu, Liu Zhaohui, Meng Yanli, Wei Qianjie, Li Chunlei, Cui Wenbin, Song Panpan, Yu Qiannan
Аннотация
BACKGROUND AND AIMS: Acute lung injury (ALI) is one of the significant pathophysiological features of renal ischemia/reperfusion (rI/R) and is the chief reason for rI/R-mediated numerous organ failures. Pyroptosis is a lethal pathogenesis of ALI in rI/R, and precise, actual treatments are deficient. While propofol (Pro) has been revealed to have anti-apoptosis and anti-necroptosis properties, it remains uncertain whether it inhibits Pyroptosis to ameliorate rI/R-induced ALI.
METHODS: Pro was intravenously treated with rats with rI/R mediated through minimally invasive vascular clipping for 45 min. Transmission electron microscopy (TEM) and histopathological evaluation were used to determine lung and rat alveolar macrophage (AM) injury. AM were subjected to hypoxia/reoxygenation (H/R) to mediate AM pyroptosis, and the cells were incubated with Pro in the presence of an inhibitor and activator of mTOR (rapamycin and MHY1485). An immunofluorescence assay was used to evaluate the mTOR cascade and pyroptotic physiology.
RESULTS: Pro significantly lessened respiratory AM injury and ALI in the rI/R rats. The TEM findings of AM displayed that Pro decreased respiratory AM pyroptosis, which was established in vitro. H/R mediated the Pyroptosis of AM and injured their paracellular permeability, and these properties were attenuated by incubating the cells with Pro. Pro's defensive action against Pyroptosis relied on the mTOR cascade. mTOR activation significantly defended pyroptotic physiology and reduced inflammatory mediators release in AM in vitro.
CONCLUSIONS: Our findings established that Pro defended rI/R-induced ALI by upregulating the mTOR pathway to incompletely attenuate AM pyroptosis and reduce ALI in the rI/R rat model.
METHODS: Pro was intravenously treated with rats with rI/R mediated through minimally invasive vascular clipping for 45 min. Transmission electron microscopy (TEM) and histopathological evaluation were used to determine lung and rat alveolar macrophage (AM) injury. AM were subjected to hypoxia/reoxygenation (H/R) to mediate AM pyroptosis, and the cells were incubated with Pro in the presence of an inhibitor and activator of mTOR (rapamycin and MHY1485). An immunofluorescence assay was used to evaluate the mTOR cascade and pyroptotic physiology.
RESULTS: Pro significantly lessened respiratory AM injury and ALI in the rI/R rats. The TEM findings of AM displayed that Pro decreased respiratory AM pyroptosis, which was established in vitro. H/R mediated the Pyroptosis of AM and injured their paracellular permeability, and these properties were attenuated by incubating the cells with Pro. Pro's defensive action against Pyroptosis relied on the mTOR cascade. mTOR activation significantly defended pyroptotic physiology and reduced inflammatory mediators release in AM in vitro.
CONCLUSIONS: Our findings established that Pro defended rI/R-induced ALI by upregulating the mTOR pathway to incompletely attenuate AM pyroptosis and reduce ALI in the rI/R rat model.