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Li X.-D.,Peking Union Medical College | Cheng Y.-T.,Capital Medical University | Yang Y.-J.,Peking Union Medical College | Meng X.-M.,Peking Union Medical College | And 5 more authors.
Microvascular Research | Year: 2012

Objective: To investigate whether ischemic preconditioning (IP) can reduce myocardial no-reflow by activating endothelial (e-) nitric oxide synthase (NOS) via the protein kinase A (PKA) pathway. Methods and Results: In a 90-min ischemia and 3-h reperfusion model, minipigs were assigned into sham, ischemia-reperfusion (IR), IR+IP, IR+IP+L-NNA (an eNOS inhibitor, 10mg.kg -1), IR+IP+H-89 (a PKA inhibitor, 1.0μ.kg -1Ķmin -1), IR+L-NNA, and IR+H-89 groups. IP pretreatment improved cardiac function and coronary blood flow, decreased the activities of creatine kinase by 36.6% after 90 min of ischemia and by 32.8% after 3 h of reperfusion (P<0.05), reduced the no-reflow areas from 49.9% to 11.0% (P<0.01), and attenuated the infarct size from 78.2% to 35.4% (P<0.01). IP stimulated myocardial PKA activities and the expression of PKA and Ser 133 phosphorylated (p-) cAMP response element-binding protein (CREB) in the reflow and no-reflow myocardium, and enhanced the activities of constitutive NOS and the phosphorylation of eNOS at Ser 1179 and Ser 635 in the no-reflow myocardium. IP suppressed the expression of tumor necrosis factor-α and P-selectin, and attenuated cardiomyocytes apoptosis by regulating the expression of Bcl-2 and caspase-3 in the reflow and no-reflow myocardium. The eNOS inhibitor L-NNA completely canceled these beneficial effects of IP without any influence on PKA activity, whereas the PKA inhibitor H-89 partially blocked the IP cardioprotective effects and eNOS phosphorylation at the same time. Conclusion: IP attenuates myocardial no-reflow and infarction after ischemia and reperfusion by activating the phosphorylation of eNOS at Ser 1179 and Ser 635 in a partly PKA-dependent manner. © 2012 Elsevier Inc.


Kang S.,Tongji University | Yang Y.-j.,Cardiovascular Institute | Wu Y.-l.,The Integration of Traditional and Western Medical Research Academy of Hebei Province | Chen Y.-t.,Cardiovascular Institute | And 2 more authors.
Microvascular Research | Year: 2010

Objectives: This study was to investigate the salvaged myocardial and microvascular endothelial cells apoptosis at the first week of reperfused acute myocardial infarction (AMI). Methods: Sixteen mini swines (20-30 kg) were randomly assigned to the sham-operated group and the AMI group. The acute myocardial infarction and reperfusion model was created, and pathologic myocardial tissue was collected at day 7 following left anterior descending coronary artery reperfusion, and detected by transmission electron microscope, in situ cell apoptosis detection (TUNEL method), Real-time Quantitative Polymerase Chain Reaction and Western blot. Results: In the AMI group, the infarcted area showed the myolysis, fibroblast and injuried endothelial cells under transmission electron microscope. The infarcted area had higher apoptotic index of microvascular endothelial cells than the marginal area, the normal area, and the sham-operated area (all P < 0.05). Fas and Bax mRNA expressions in the infarcted area were higher than those in the marginal area, the normal area, and the sham-operated area (all P < 0.05), and both protein overexpressions and Bcl-2 low expression in the infarcted and marginal areas compared with the normal area and the sham-operated area. Conclusions: The overexpressions of Fas and Bax or the low expression of Bcl-2 in the infarcted and marginal heart tissue may play an important role in the acceleration of myocardial and endothelial apoptosis at 7th day following reperfused acute myocardial infarction. © 2009 Elsevier Inc. All rights reserved.


Shen D.-F.,Renmin University of China | Shen D.-F.,The Fifth Teaching Hospital of Xinjiang Medical UniversityXinjiang | Ni J.,Renmin University of China | Ni J.,Hubei University | And 14 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2016

Shensongyangxin (SSYX) is a Chinese medicine compound used to treat cardiac tachyarrhythmias. We have previously demonstrated that SSYX can protect cardiomyocytes against pressure overload-induced cardiac hypertrophy. However, whether SSYX exerts an effect on lipopolysaccharide (LPS)-induced myocardial injury remains unknown. H9c2 rat cardiomyocytes were subjected to LPS in the presence or absence of different SSYX concentrations (0.1, 10, 50, and 100 μg/mL). By CCK-8 testing, TUNEL staining, Polymerase chain reaction (PCR) and Western blot analyses showed that 0.1, 10, 50, or 100 μg/mL SSYX did not affect the cell viability. However, LPS increased the release of TNF-α, IL-1β, and IL-6 from cardiomyocytes, which were attenuated by 10 and 50 μg/mL SSYX pretreatment. Moreover, SSYX protected cardiomyocytes against mitochondrial apoptosis by inhibiting the elevation of Bax and c-caspase3 as well as the decrease of Bcl-2. LPS-induced NFκB activation was abolished by SSYX, as well as by the NFκB inhibitor, Bay117082, which also mitigated the pro-inflammatory and pro-apoptotic effects of LPS. Results indicate that the activation of NFκB may be responsible for LPS-induced cardiac injury. Therefore, SSYX conferred a protecting effect on cardiomyocytes exposed to LPS possibly by inhibiting the NFκB pathway. © 2016, E-Century Publishing Corporation. All Rights Reserved.


Chen S.,CAS Dalian Institute of Chemical Physics | Wei C.,The Integration of Traditional and Western Medical Research Academy of Hebei Province | Gao P.,CAS Dalian Institute of Chemical Physics | Kong H.,CAS Dalian Institute of Chemical Physics | And 5 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

The present study aimed to investigate the anti-depressive effect of the traditional Chinese medicine Allium macrostemon in a rat model of depression induced by exposure to chronic immobilization stress. Lipid and acylcarnitine metabolism were set into the focus of this study due to their key role in the pathogenesis of depression. Plasma lipid profiling was performed by ultra fast liquid chromatography/ion trap-time of flight mass spectrometry. Ultra-high performance liquid chromatography/triple quadrupole mass spectrometry was used to characterize the plasma acylcarnitine profile. Principal component analysis (PCA) revealed distinct differences in plasma lipid and acylcarnitine profiles of depressed rats from those in the control rats, which were also validated by univariate analysis. Several lysophosphatidylcholines (LPC (18:1→:2), LPC (20:1), LPC (O-16:2), and LPC (O-18:3)) as well as most medium- and long-chain acylcarnitines were elevated, while some phosphatidylcholines (PC (32:1), PC (36:4→:5), PC (37:4), PC (38:4→:6), PC (40:6), PC (O-36:4), and PC (O-38:5)) and triglycerides (TG (58:12), TG (60:12), and TG (62:13→:14)) were decreased in the plasma of depressed rats. These changes indicate that depressed rats were associated with inflammatory conditions and an incomplete β-oxidation of fatty acids. Most of these dysregulated metabolites were returned to their normal levels after treatment with A. macrostemon according to PCA and univariate analysis, highlighting the anti-depressive effect of this traditional Chinese medicine. These results show that liquid chromatography/mass spectrometry-based quantitative metabolic profiling method is a useful tool to investigate the metabolic changes in depression and the anti-depressive effect of traditional Chinese medicine. © 2013 Elsevier B.V.


Dai W.,CAS Dalian Institute of Chemical Physics | Zhang F.,CAS Dalian Institute of Chemical Physics | Jia Z.,The Integration of Traditional and Western Medical Research Academy of Hebei Province | Wei C.,The Integration of Traditional and Western Medical Research Academy of Hebei Province | And 4 more authors.
Chinese Journal of Chromatography (Se Pu) | Year: 2011

Excess fatigue is a pathological state of continuing accumulation of fatigue, which may cause the deterioration of body health, occurrence of diseases, and even lead to death. A metabonomics study was performed on the excess fatigue rats treated with traditional Chinese medicine Tongxinluo or ginseng based on ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC-IT-TOF-MS). The plasma metabolic profiling data of the control rats, excess fatigue rats, and excess fatigue rats treated with Tongxinluo or ginseng were acquired. The orthogonal partial least squares analysis (OPLS) was applied for the multivariate statistics and the discovery of important differential metabolites distinguishing the excess fatigue rats treated with Tongxinluo or ginseng from the control rats and excess fatigue rats. The results showed tryptophan, bile acid, lysophosphatidylcholine metabolism were disturbed in the excess fatigue rats. The metabolic pattern including the related metabolic pathways of the rats, being treated with Tongxinluo or ginseng, was adjusted towards the normal state.

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