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bioRxiv · 10.1101/2023.11.13.566957

The Shexiang Baoxin Pill Protects Myocardial Cells from Multiple Targets of MIRI through the PI3K/Akt/eNOS Signal Pathway

wei, n.·liu, z. b.·li, s. y.·Gao, y.
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Abstract

BackgroundMyocardial ischemia-reperfusion injury (MIRI) can significantly aggravate myocardial injury in patients with ST-segment elevation myocardial infarction (STEMI). At present, there are few effective treatments for MIRI. The Shexiang Baoxin Pill (SBP) can reduce MIRI. The PI3K/Akt/eNOS signaling pathway, inflammation, oxidative stress, and apoptosis are all involved in the regulation of MIRI. SBP has multi-component, multi-target, and synergistic effects, but its mechanism of action on MIRI has not been reported. PurposeWe sought to explore whether SBP exerts a protective mechanism by inhibiting the inflammatory reaction, oxidative stress, and apoptosis, reducing MIRI through the PI3K/Akt/eNOS signal pathway. Materials and methodsHypoxia-reoxygenation (H/R) H9c2 cardiomyocytes were used as an in vitro model of MIRI. The active components of Shexiang Baoxin pills were extracted with water. The levels of phosphorylated proteins and genes related to the PI3K/Akt/eNOS pathway were measured by Western blotting and real-time fluorescence quantitative PCR. Cell viability, apoptosis rates, and apoptosis-related proteins (Bcl-2, Bax, Caspase-3) were detected by CCK-8, flow cytometry, and Western blotting. The expression of reactive oxygen species (ROS), homocysteine (Hcy), malondialdehyde (MDA), and gp91phox was detected by fluorescence probe, ELISA, TBA, and Western blotting. The levels of inflammatory factors (TNF-, IL-6, IL-18) were measured by an ELISA method. ResultsSBP increased the cell survival rate of H/R cardiomyocytes, reduced the injury to H/R cardiomyocytes, and increased the protein phosphorylation levels of p-PI3KY607, p-AktSer473, p-eNOSSer1177, and mRNA of H/R cardiomyocytes. In addition, SBP increased the level of Bcl-2 protein and the Bcl-2/Bax ratio and decreased the apoptosis rate and Bax and Caspase-3 expression. It reduced the levels of oxidative stress indexes (ROS, HCY, MDA, and gp91phox) and inflammatory factors (TNF-, IL-6, IL-18) and enhanced antioxidant stress, anti-apoptosis, and an anti-inflammatory reaction. The above effects were attenuated after the inhibition of the PI3K/Akt/eNOS signal pathway. ConclusionWe established that SBP extract inhibited oxidative stress, inflammatory response, and apoptosis through the PI3K/Akt/eNOS signal pathway and alleviated the injury of H9c2 cells induced by hypoxia-reoxygenation.

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wei, n., liu, z. b., li, s. y., Gao, y.. 2023-11-14. The Shexiang Baoxin Pill Protects Myocardial Cells from Multiple Targets of MIRI through the PI3K/Akt/eNOS Signal Pathway. https://doi.org/10.1101/2023.11.13.566957

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