Abstract
Acute inflammation is an important component of the pathogenesis of hepatic ischemia/reperfusion injury (HIRI). Magnesium lithospermate B (MLB) has strong neuroprotective and cardioprotective effects. The purpose of this study was to determine whether MLB had underlying protective effects against hepatic I/R injury and to reveal the potential mechanisms related to the hepatoprotective effects. In this study, we first examined the protective effect of MLB on HIRI in mice that underwent 1 h ischemia followed by 6 h reperfusion. MLB pretreatment alleviated the abnormal liver function and hepatocyte damage induced by I/R injury. We found that serum inflammatory cytokines, including IL-6, IL-1β, and TNF-α, were significantly decreased by MLB during hepatic ischemia/reperfusion (I/R) injury, suggesting that MLB may alleviate hepatic I/R injury via inhibiting inflammatory signaling pathways. Second, we investigated the protein level of p-Jak2/Jak2 and p-Stat3/Stat3 using Western blotting and found that MLB could significantly inhibit the activation of the Jak2/Stat3 signaling pathway, which was further verified by AG490 in a mouse model. Finally, the effect of MLB on the Jak2/Stat3 pathway was further assessed in an in vitro model of RAW 264.7 cells; 1 µg/ml LPS induced the secretion of inflammatory mediators, including IL-6, TNF-α, and activation of the Jak2/Stat3 signaling pathway. MLB significantly inhibited the abnormal secretion of inflammatory factors and the activation of the Jak2/Stat3 signaling pathway in RAW264.7 cells. In conclusion, MLB was found for the first time to reduce inflammation induced by hepatic I/R via suppressing the Jak2/Stat3 pathway.
Highlights
Hepatic ischemia/reperfusion injury (HIRI) is a major complication during various diseases and liver surgery procedures, such as hemorrhagic shock, trauma, liver transplantation, and hepatectomy (Arkadopoulos et al, 2011; Douzinas et al, 2012; Lu et al, 2018)
Levels (Figure 2A–C) were not significantly different in the sham+Magnesium lithospermate B (MLB) group compared to the sham group, suggesting that MLB has no adverse effect on the function of the mouse liver
MLB is a hydrophilic constituent of Salvia miltiorrhiza, which was widely used for the treatment of cardiovascular and cerebrovascular disease (Zhu Jinqiang, 2010)
Summary
Hepatic ischemia/reperfusion injury (HIRI) is a major complication during various diseases and liver surgery procedures, such as hemorrhagic shock, trauma, liver transplantation, and hepatectomy (Arkadopoulos et al, 2011; Douzinas et al, 2012; Lu et al, 2018). Ischemic preconditioning and pharmacological agents are employed in clinics to prevent and mitigate I/R injury (Li et al, 2015). Ischemic preconditioning is effective only in some young patients (Clavien et al, 2003), and the efficacy of available drugs is limited. There is no well-established method to prevent and mitigate I/R injury, which will improve the safety of major liver surgery and liver transplantation (Robertson et al, 2017). There is an urgent need to find effective methods/ drugs for the treatment of hepatic I/R injury
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