ERK1/2 mediates edaravone-triggered protection against myocardial damage induced by isoprenaline in H9c2 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of extracellular signal regulated kinase 1/2 (ERK1/2) on edaravone (EDA)-triggered protection against myocardial toxicity induced by isoprenaline (ISO) in H9c2 myocardial cells (H9c2 cells).</p><p><b>METHODS</b>H9c2 cells were exposed to ISO at different concentrations to establish a cardiac toxicity model induced by persistent excitation of β1 receptor. EDA was added before ISO as a pretreatment. PD-98059, an ERK1/2 inhibitor, was administered 1 h prior to EDA to inhibit the phosphorylation of ERK1/2. Cell viability was measured using cell counter kit (CCK-8). The expressions of p-ERK1/2 and t-ERK1/2 were tested by Western blotting. Mitochondrial membrane potential (MMP) was detected by Rhodamine123 (Rh123) staining and photofluorography.</p><p><b>RESULTS</b>Exposure of H9c2 cells to 80 µmol/L ISO for 24 h down-regulated ERK1/2 phosphorylation and repressed MMP. Pretreatment with 10-40 µmol/L EDA for 1 h inhibited ISO-induced myocardial toxicity and pretreatment of 40 µmol/L EDA partially rescued ERK1/2 phosphorylation and MMP level. PD-98059 abolished cardiac protection of EDA, leading to myocardial toxicity and MMP loss.</p><p><b>CONCLUSION</b>EDA can protect H9c2 cells against myocardial injury induced by ISO by suppressing ISO-triggered inhibition of ERK1/2 activation.</p>

Reactive oxygen species scavenger protects cardiac cells against injuries induced by chemical hypoxia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), against H9c2 cardiomyocytes from injuries induced by chemical hypoxia.</p><p><b>METHODS</b>H9c2 cells were treated with cobalt chloride (CoCl2), a chemical hypoxia-mimetic agent, to establish the chemical hypoxia-induced cardiomyocyte injury model. NAC was added into the cell medium 60 min prior to CoCl2 exposure. The cell viability was evaluated using cell counter kit (CCK-8), and the intercellular ROS level was measured by 2', 7'- dichlorfluorescein-diacetate (DCFH-DA) staining and photofluorography. Mitochondrial membrane potential (MMP) of the cells was observed by Rhodamine123 (Rh123) staining and photofluorography, and the ratio of GSSG/ (GSSG+GSH) was calculated according to detection results of the GSSG kit.</p><p><b>RESULTS</b>Exposure of H9c2 cardiomyocytes to 600 micromol/L CoCl2 for 36 h resulted in significantly reduced cell viability. Pretreatment with NAC at the concentrations ranging from 500 to 2000 micromol/L 60 min before CoCl2 exposure dose-dependently inhibited CoCl2-induced H9c2 cell injuries, and obviously increased the cell viability. NAC at 2000 micromol/L obviously inhibited the oxidative stress induced by CoCl2, decreased the ratio of GSSG/(GSSG+GSH), increased ROS level, and antagonized CoCl2-induced inhibition on MMP.</p><p><b>CONCLUSION</b>NAC offers obvious protective effect on H9c2 cardiomyocytes against injuries induced by chemical hypoxia by decreasing in the ratio of GSSG/(GSSG+GSH) and ROS level and ameliorating MMP.</p>

Electroacupuncture treatment of chronic insomniacs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Due to the quick rhythm of life and work pressure, more and more people suffer from sleep quality problems. In this study, we investigated the effect of electroacupuncture on sleep quality of chronic insomniacs and the safety of electroacupuncture therapy.</p><p><b>METHODS</b>Four courses of electroacupuncture treatment were applied to 47 patients. With pre-treatment and post-treatment self-control statistical method, Pittsburgh sleep quality index (PSQI) scores were used for evaluating sleep quality. Polysomnogram was used for detecting insomniacs' changes in sleep architecture. The safety of electroacupuncture was evaluated by monitoring the self-designed adverse events and side effects during treatment and post-treatment.</p><p><b>RESULTS</b>Electroacupuncture considerably improved insomniacs' sleep quality and social function during the daytime. Electroacupuncture had certain repairing effect on the disruption in sleep architecture. At the same time, electroacupuncture prolonged slow wave sleep (SWS) time and relatively rapid eye movement sleep (REM sleep) time. There was no hangover, addiction or decrements in vigilance during the daytime (incidence rate was 0). However, insomnia rebound rate was about 23% within one month.</p><p><b>CONCLUSIONS</b>These results suggest that electroacupuncture has beneficial effect on sleep quality improvement in the patients with chronic insomnia, which may be associated with repairing sleep architecture, reconstructing sleep continuity, as well as prolonging SWS time and REM sleep time. Electroacupuncture treatment for chronic insomnia is safe. Therefore, electroacupuncture therapy could be a promising avenue of treatment for chronic insomnia.</p>

Effects of angiotensin-(1-7) on oxidative stress and functional changes of isolated rat hearts induced by ischemia-reperfusion / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of angiotensin (Ang)-(1-7) on oxidative stress and functional changes in isolated rat hearts with myocardial ischemia-reperfusion (IR) injury.</p><p><b>METHODS</b>IR injury was induced in isolated rat hearts with the Langendorff' apparatus. The left ventricular systolic pressure (LVSP) of the rat heart was measured using a pressure transducer. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in the myocardium were detected using commercial kits.</p><p><b>RESULTS</b>Myocardial ischemia (15 min) and reperfusion (30 min) significantly increased myocardial levels of MDA, and reduced the SOD activity and LVSP (P<0.05). Pretreatment with Ang-(1-7) at 1.0 nmol/L 30 min before ischemia obviously inhibited IR-induced MDA increment and lowering of SOD activity and LVSP. Pretreatment of the rats with intraperitoneal injection of 5 mg/kg indomethacin 1 h before isolation of the heart markedly antagonized the effect of Ang-(1-7) on MDA production, SOD activity and LVSP.</p><p><b>CONCLUSION</b>Angiotensin-(1-7) can inhibit IR injury-induced oxidative stress and decrease in cardiac contractile function in isolated rat hearts. The mechanism underlying the effect of Ang-(1-7) may be associated with increased secretion of prostaglandin.</p>

Increased brachial-ankle pulse wave velocity is associated with impaired endothelial function in patients with coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulse wave velocity and flow-mediated vasodilation (FMD) are widely used as noninvasive modalities for evaluating atherosclerosis. However, it is not known whether pulse wave velocity is related to FMD in patients with coronary artery disease (CAD). Therefore, the present study was designed to investigate the alteration in brachial-ankle pulse wave velocity (baPWV) and endothelial function in CAD patients.</p><p><b>METHODS</b>Thirty-three patients with CAD and thirty control subjects were recruited for this study. baPWV was measured non-invasively using a VP 1000 automated PWV/ABI analyzer (PWV/ABI, Colin Co. Ltd., Komaki, Japan). Endothelial function as reflected by FMD in the brachial artery was assessed with a high-resolution ultrasound device.</p><p><b>RESULTS</b>baPWV was increased in CAD patients compared with control subjects [(1756.1 +/- 253.1) cm/s vs (1495.3 +/- 202.3) cm/s, P < 0.01]. FMD was significantly reduced in CAD patients compared with control subjects [(5.2 +/- 2.1)% vs (11.1 +/- 4.4)%, P < 0.01]. baPWV correlated with FMD (r = -0.68, P < 0.001). The endothelium-independent vasodilation induced by sublingual nitroglycerin in the brachial artery was similar in the CAD group compared with the control group.</p><p><b>CONCLUSIONS</b>CAD is associated with increased baPWV and endothelial dysfunction. Increased baPWV parallels diminished endothelial function. Our data therefore suggest that baPWV can be used as a noninvasive surrogate index in clinical evaluation of endothelial function.</p>

Effects of ACE inhibitor on the calcium transient and calcium handling proteins in ventricular myocytes from rats with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transient and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.</p><p><b>METHODS</b>Male Wistar rats were randomized to heart failure group treated with perindopril (CHF-T, 3 mg.kg(-1).d(-1)), heart failure group without treatment (CHF-C) and sham-operated group (PS) after heart failure was induced by constricting abdominal aorta for 16 weeks. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated, and single cell shortening fraction and [Ca(2+)](i) were simultaneously measured through laser scanning confocal microscope under the field stimulation (1.0 Hz). RT-PCR and Western blot were performed to evaluate the level of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX(1)), sarcoplasmic Ca(2+)-ATPase (SERCA(2)) and phospholamban (PLB).</p><p><b>RESULTS</b>The fraction of cell shortening (FS%) and [Ca(2+)](i max) (nmol/L) were significantly smaller in group CHF-C than group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)](i max): 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01). And in CHF-T group, FS and [Ca(2+)](i max) were greater than those in CHF-C group. In CHF-C group, the left ventricular mRNA of NCX(1) and PLB were significantly higher than those in PS group (R(NCX)(1)/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; R(PLB)/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P = 0.045), yet SERCA(2) mRNA was lower than PS group (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). In CHF-T group, the mRNA levels of NCX(1) and SERCA(2) were just in the midst of the CHF-C and PS group, and had statistical significance respectively (all P < 0.05). In CHF - C and CHF - T group, the protein levels of NCX(1) were 1.141 +/- 0.047 and 1.074 +/- 0.081 times PS group, respectively (both P < 0.05), and SERCA(2) protein levels were respectively 0.803 +/- 0.100 and 0.893 +/- 0.084 times as high as in PS group (both P < 0.05). The protein expression of NCX(1) and SERCA(2) were also different between CHF-C and CHF-T groups (both P < 0.05).</p><p><b>CONCLUSION</b>ACE inhibitor could improve cardiac function in CHF through directly enhancing the contractility of single myocardial cell, and these effects were probably mediated by its role in preventing the deleterious changes of calcium transient and calcium handling proteins in CHF.</p>

Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.</p><p><b>METHODS</b>Male Wistar rats were randomized to heart failure group treated with perindopril [CHF-T, 3 mg.kg(-1).d(-1)], heart failure group without treatment (CHF-C) and sham-operated group (PS). Heart failure was induced by abdominal aortic constriction. All groups were further followed up for 12 weeks. Left ventricular myocytes were then isolated. Single cell shortening fraction and [Ca(2+)]i were simultaneously measured by laser scanning confocal microscope under the field stimulation (1.0 Hz). Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were performed to evaluate the changes of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX1), sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) and phospholamban (PLB).</p><p><b>RESULTS</b>The fraction of cell shortening (FS%) and [Ca(2+)]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)]i max: 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; RPLB/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P < 0.05), while SERCA2 mRNA was downregulated (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P < 0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141 +/- 0.047 and 1.074 +/- 0.081 times of that in PS group respectively (both P < 0.05), and SERCA2 protein levels were 0.803 +/- 0.100 and 0.893 +/- 0.084 times of that in PS group respectively (both P < 0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P < 0.05).</p><p><b>CONCLUSION</b>ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.</p>