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Panax notoginseng saponins (PNS), the main active ingredient extracted from the Chinese herb SanQi, has antiapoptotic, antioxidant, and anti-inflammatory effects to protect the heart from myocardial ischemia/reperfusion injury (MIRI). ATP-sensitive potassium (KATP) channel plays an important role in pharmacological preconditioning against MIRI. However, its effect on inflammation induced by MIRI remains elusive. Thus, we hypothesise that PNS alleviates the inflammatory response induced by MIRI, and KATP channels play a crucial role in it.The rat MIRI model was established by 40 min left anterior descending coronary artery occlusion followed by 60 min reperfusion. PNS was administered 30 min before ischemia, glibenclamide was administered 10 min before PNS. Cardiac function, myocardial histology, and MPO activity were evaluated. The levels of inflammatory mediators TNF-α and MCP-1 in myocardium were measured by ELISA. The protein and gene expression of KATP channel subunits were determined by Western blot analysis and real-time PCR.PNS pretreatment ameliorated cardiac function and myocardial pathological changes, decreased myocardial MPO activity and inhibited the gene and protein expression of TNF-α and MCP-1. Importantly, PNS increased the expression of the KATP channel. The non-selective KATP channel blocker glibenclamide could block the cardioprotection of PNS.PNS preconditioning may reduce inflammation to due to MIRI via KATP channels.Supported by a project grant from National Natural Science Foundation (NSFC) of China (Grant No. 81303256).