Objective Puerarin was reported to protect against myocardial ischemia/reperfusion (IR) injury. The current study aims to investigate the protective effects of puerarin against myocardial IR injury and the underlying mechanisms. Methods The hearts were subjected to the ligation of the left anterior descending coronary artery and reperfusion. Before reperfusion, pretreatment with puerarin (100 mg/kg), with or without the AMPK inhibitor Compound c (0.25 mg/kg). Myocardial infarct size, the serum creatine kinase-MB (CK-MB) activity, cardiac function, apoptotic cell death, and the endoplasmic reticulum stress, as well as activation of the AMPK/NRF2 pathway were observed. Results Treatment with puerarin significantly decreased the myocardial infarct size, the serum CK-MB activity and notably alleviated IR-induced cardiac dysfunction. Moreover, puerarin reduced myocardial IR-induced apoptotic cell death. In addition, puerarin inhibited myocardial IR-induced endoplasmic reticulum stress and activated the AMPK/NRF2 pathway. More importantly, the AMPK inhibitor Compound c prevented these puerarin-induced cardioprotective effects and activation of the AMPK/NRF2 pathway, as well as apoptosis and the endoplasmic reticulum stress activation. Conclusion Our results show that puerarin alleviates myocardial IR injury by inhibiting apoptosis and endoplasmic reticulum stress via the AMPK/NRF2 pathway.

Introduction and Objective: Dexmedetomidine (Dex) and a number of miRNAs contribute to ischemia/reperfusion injury. We aimed to explore the role of Dex and miR-146a on myocardial cells injured by hypoxia/reoxygenation (H/R). Method: H9C2 cells were injured by H/R. Cell viability was tested using the cell counting kit-8. Lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were determined using commercial kits. Flow cytometry was performed to determine apoptosis rate and reactive oxygen species (ROS) level. Protein and mRNA levels were assessed using Western blot and qPCR. Results: miR-146a expression and cell viability of H9C2 cells were downregulated under the circumstance of H/R injury. The tendency could be reversed by Dex, which could also upregulate SOD activity and decrease apoptosis, LDH activity, MDA, 78-kDa glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP) levels of H9C2 cells. GRP78, CHOP levels, and cell viability were negatively modulated by miR-146a. Dex elevated cell viability, catalase, MnSOD, and NAD(P)H dehydrogenase (NQO1) levels but suppressed apoptosis rate, GRP78, and CHOP levels by increasing miR-146a expression and downregulating ROS, phosphorylation of p38, and extracellular signal-regulated kinases 1/2 levels. By using SB203580 (SB), the p38 mitogen-activated protein kinase (MAPK) inhibitor, Dex or the inhibition of miR-146 upregulated cell viability but downregulated GRP78 and CHOP levels. Conclusion: Dex might regulate miR-146a expression, which could further modulate the endoplasmic reticulum stress and oxidative stress and eventually affect the cell viability and apoptosis of myocardial cells injured by H/R via the MAPK signal pathway.

LIM‐domain proteins have been shown to be associated with heart development and diseases. Systematic studies of LIM family members at the genome‐wide level, which are crucial to further understand their functions in cardiac hypertrophy, are currently lacking. Here, 70 LIM genes were identified and characterised in mice. The expression patterns of LIM genes differ greatly during cardiac development and in the case of hypertrophy. Both Crip2 and Xirp2 are differentially expressed in cardiac hypertrophy and during heart failure. In addition, the hypertrophic state of cardiomyocytes is controlled by the relative expression levels of Crip2 and Xirp2. This study provides a foundation for further understanding of the special roles of LIM proteins in mammalian cardiac development and hypertrophy.

目的 探讨葛根素(puerarin,Pue)改善大鼠心脏缺血再灌注(ischemia reperfusion,IR)损伤和减轻线粒体氧化应激的作用.方法 采用SD大鼠离体心脏缺血再灌注模型,30只SD大鼠随机分为3组:正常对照组(control)、缺血再灌注模型组(IR)和葛根素处理缺血再灌注组(Pue+IR).TTC染色、LDH含量检测和HE染色评价心肌损伤程度.左室压力反映心脏功能.TUNEL染色法检测细胞凋亡率.ELISA检测线粒体丙二醛(MDA)和过氧化氢(H2 O2)含量、超氧化物歧化酶(SOD)活性和ATP含量.结果 与control组相比,IR组心肌梗死面积、冠脉流出液中LDH含量和细胞凋亡率明显增加(均P<0.01),而心脏功能显著降低(P<0.01),HE染色显示心肌纤维断裂明显,同时,线粒体MDA和H2 O2含量显著增加,SOD活性和ATP含量明显降低(均P<0.01).与IR组比较,Pue+IR组心肌梗死面积、冠脉流出液中LDH含量以及细胞凋亡率显著降低(P<0.01),心脏功能被改善(P<0.01),心肌纤维断裂减轻,线粒体MDA和H2O2含量降低(P<0.01),SOD活性和ATP含量增加(P<0.01).结论 Pue可以改善心肌缺血再灌注损伤,其作用机制可能与减轻线粒体氧化应激、减少细胞凋亡、提高ATP含量增强心脏功能有关.

Aims: The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury. Main methods: C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinaseMB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-kappa B pathway. Results: Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-alpha, IL-6, and IL-113, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-kappa B, NLRP3, cleaved caspase-1, cleaved IL 113, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-kappa B pathway, as well as the NLRP3 inflammasome activation. Conclusion: Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-kappa B pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.

Aims: Studies on the prognostic significance of circulating pentraxin-3 level in patients with coronary artery disease (CAD) have yielded conflicting results. The aim of this meta-analysis was to evaluate the prognostic value of circulating pentraxin-3 level in CAD patients. Materials/methods: We made a systematic literature search in Pubmed, Embae, CNKI, Wanfang, and VIP database from their inception to January 10, 2019 for prospective cohort studies that investigated the association between pentraxin-3 level and adverse outcomes in patients with CAD. The outcome measures were all-cause mortality, cardiac death, and cardiac events (cardiac death, nonfatal myocardial infarction, heart failure or coronary revascularization). Multivariable-adjusted risk ratio (RR) with 95% confidence intervals (CI) was pooled for the highest versus the lowest pentraxin-3 group to summarize the predictive value. Results: Nine studies were included, enrolling 5,174 CAD patients. Overall, CAD patients with the highest pentraxin-3 level had an increased risk of all-cause mortality (RR 1.81; 95% CI 1.43-2.28), cardiac death (RR 1.77; 95% CI 1.38-2.26), and cardiac events (RR 1.61; 95% CI 1.16-2.25). However, elevated pentraxin-3 level appeared to not significantly increase the risk of cardiac events (RR 1.63; 95% CI 0.71-3.72) in stable CAD subgroup. Conclusions: In CAD patients, elevated circulating pentraxin-3 level is possibly an independent predictor of all cause mortality, cardiac death, and cardiac events. However, interpretation of these findings should be with caution due to the small number of studies analyzed.