Abstract
Inflammatory response during myocardial ischemia reperfusion injury (MIRI) is essential for cardiac healing, while excessive inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanism of these uncontrolled inflammatory processes has a significant impact during the MIRI therapy. Here, we found a critical role of ATP-sensitive potassium channels (KATP) in the inflammatory response of MIRI and its potential mechanism and explored the effects of Panax Notoginseng Saponins (PNS) during this possess. Rats underwent 40 min ischemia by occlusion of the left anterior descending (LAD) coronary artery and 60 min of reperfusion. PNS was treated at the corresponding time point before operation; 5-hydroxydecanoate (5-HD) and glybenclamide (Gly) (or Nicorandil (Nic)) were used as pharmacological blocker (or nonselective opener) of KATP. Cardiac function and pathomorphology were evaluated and a set of molecular signaling experiments was tested. KATP current density was measured by patch-clamp. Results revealed that in MIRI, PNS pretreatment restored cardiac function, reduced infarct size, and ameliorated inflammation through KATP. However, inhibiting KATP by 5-HD and Gly significantly reversed the effects, including NLRP3 inflammasome and inflammatory mediators IL-6, MPO, TNF-α, and MCP-1. Moreover, PNS inhibited the phosphorylation and nuclear translocation of NF-κB in I/R myocardium when the KATP was activated. Importantly, PNS promoted the expression of subunits and activation of KATP. The study uncovered KATP served as a new potential mechanism during PNS modulating MIRI-induced inflammation and promoting injured heart recovery. The manipulation of KATP could be a potential therapeutic approach for MIRI and other inflammatory diseases.
Highlights
Coronary heart disease (CHD) is a major disease with high morbidity and mortality worldwide [1]
The results indicated that KATP channels were opened in the I/R group, in contrast to those in the control group (p < 0:05), and Panax Notoginseng Saponins (PNS) (100 mg/L) could further upregulate the potassium current mediated by the KATP channel (p < 0:05 vs. I/R group) Figures 4(j), 4(k)
We found that PNS could significantly inhibit inflammatory body NLRP3 and the classic inflammatory factor Interleukin-6 (IL-6), and the anti-inflammatory effect was inhibited by KATP blockers 5-HD and Gly (Figures 5(a)–5(c))
Summary
Coronary heart disease (CHD) is a major disease with high morbidity and mortality worldwide [1]. The use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing myocardial infarct and improving clinical outcomes. During this period, it will inevitably cause myocardial ischemia-reperfusion injury (MIRI). MIRI is not always immediately lethal, it often leads to delayed cardiomyocyte death by necrosis and uncontrolled inflammation, causing permanent injury to the myocardium. Studies have shown that ischaemic preconditioning (IPC) [2] and pharmacological preconditioning can significantly alleviate MIRI [3] and that the opening of the KATP channel plays an important role in their endogenous cardioprotection mechanisms [4]. It is not clear that the role of KATP protects myocardium from inflammation induced by MIRI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
