RNA-seq based transcriptomic map reveals multiple pathways of necroptosis in treating myocardial ischemia reperfusion injury.

Necroptosis has been shown to contribute to myocardial ischemia reperfusion injury (MIRI). This study aims to gain new insights into the signaling pathway of necroptosis in rat MIRI using RNA sequencing. MIRI was induced in male rats by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 120 min. RNA sequencing was performed to obtain mRNA profiles of MIRI group and MIRI group treated with necrostatin-1 (Nec-1,an inhibitor of necroptosis). Differentially expressed genes (DEGs) were then identified. The DEGs were prominently enriched in the TNF-α signaling pathway, the MAPK signaling pathway and cytokine-cytokine receptor pathways. The majority of the results were associated with genes like Thumpd3,Egr2,Dot1l,Cyp1a1,Dbnl,which primarily regulate inflammatory response and apoptosis, particularly in myocardium. The above results suggested that Nec-1 might be involved in the regulation of necroptosis and the inflammatory response through the above-mentioned genes.

Propofol pretreatment alleviates mast cell degranulation by inhibiting SOC to protect the myocardium from ischemia-reperfusion injury.

Propofol (PPF) has a protective effect on myocardial ischemia-reperfusion (I/R) injury (MIRI). The purpose of this study was to investigate whether the myocardial protective effect of propofol is related to the inhibition of mast cell degranulation and explore the possible mechanisms involved. Our in vivo results showed that compared with the sham group, cardiac function, infarct size, histopathological damage, apoptosis, and markers of myocardial necrosis were significantly increased in the ischemia-reperfusion group, and propofol pretreatment alleviated these effects. In the coculture system, propofol-treated mast cells reduced their tryptase activity, resulting in cardiomyocyte protective effects, such as decreased apoptosis of cardiomyocytes and decreased expression of myocardial necrosis markers. Finally, experimental results in vitro revealed that thapsigargin (TG) can increase mast cell degranulation, tryptase release, calcium ion concentration, and the expression of STIM1 and Orai1 induced by H/R, but propofol pretreatment can partially reverse the above effects. These results suggested that the cardioprotective effect of propofol is achieved in part by inhibiting calcium influx through store-operated Ca2+ channels (SOCs) and thus alleviating mast cell degranulation.