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1.
Mol Med Rep ; 13(5): 3993-4000, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27035121

RESUMO

Oxidative stress has been demonstrated to be important during myocardial ischemia/reperfusion injury (MIRI). The lazaroid U83836E, which combines the amino functionalities of the 21­aminosteroids with the antioxidant ring portion of vitamin E, is a reactive oxygen species scavenger. The aim of the current study was to investigate the effect of U83836E on MIRI and its mechanisms of action. Rat hearts were subjected to 30 min ligation of the left anterior descending coronary artery, followed by 2 h reperfusion. The results demonstrated that at 5 mg/kg, U83836E markedly protected cardiac function in ischemia/reperfusion rat models, decreased the malondialdehyde content and creatinine kinase activity, while increasing superoxide dismutase and glutathione peroxidase activity. Additionally, U83836E significantly decreased the histological damage to the myocardium, reduced the area of myocardial infarction in the left ventricle and modified the mitochondrial dysfunction. Furthermore, U83836E enhanced the translocation of protein kinase Cε (PKCε) from the cytoplasm to the membrane. However, the cardioprotective effects of U83836E were reduced in the presence of the PKC inhibitor, chelerythrine (1 mg/kg). Therefore, the results of the present study suggest that U83836E has a potent protective effect against MIRI in rat models through the direct anti­oxidative stress mechanisms and the activation of PKC signaling.


Assuntos
Cromanos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Piperazinas/farmacologia , Proteína Quinase C-épsilon/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Membrana Celular/enzimologia , Citoplasma/enzimologia , Ativação Enzimática/efeitos dos fármacos , Masculino , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
2.
Biosens Bioelectron ; 66: 417-22, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25497981

RESUMO

A simple glassy carbon electrode (GCE) modified with gold submicron particles (AuSPs), characterized by a mean diameter of about0.15-0.20µm has been developed. Herein, the complexation reaction of Ca(2+) with alizarin red S (ARS), in 0.1M KOH, has been followed by electrochemical methods using the modified electrode which is able to catalyze the electro-reduction of ARS. When the stoichiometry ratio of Ca(2+) and ARS is 1:2, a new reduction peak at a higher negative potential of -0.975V appeared, and the peak of ARS at -0.815V disappeared. The peak current of ARS in alkaline solution is proportional to the concentration of Ca(2+) in the range 6.0×10(-7)-1.2×10(-4)M with a limit of detection (LOD) of 5.1×10(-7)M. Furthermore, the complex site of Ca(2+) with ARS was analysized by the experimental UV-vis and infrared spectrums and those calculated electronic and vibrational spectroscopies with density functional theory (DFT). The good accordance between theoretical and experimental data confirms that chelation of calcium ion preferentially occurs at the deprotonated catechol site. Then, we implemented an electrochemical assay for the investigation of Ca(2+) in preparations of isolated rat heart mitochondria, which demonstrates the submicron particles modified electrode is a simple and rapid sensor for determining the Ca(2+) in the biological samples.


Assuntos
Antraquinonas , Técnicas Biossensoriais/métodos , Cálcio/análise , Ouro , Mitocôndrias Cardíacas/química , Animais , Técnicas Biossensoriais/instrumentação , Corantes , Técnicas Eletroquímicas/instrumentação , Técnicas In Vitro , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Espectrofotometria Infravermelho
3.
Artigo em Chinês | MEDLINE | ID: mdl-24741986

RESUMO

OBJECTIVE: To investigate the effect of ischemic postconditioning on the expression of rat myocardium matris metalloproteinase-2 (MMP-2) induced by ischemia/reperfusion (I/R) and relationship between its expression and interstitium and the effect on left ventricular function. METHODS: Twenty-four rats were randomly divided into 3 groups (n = 8): sham control (SC) group, ischemic/reperfusion (I/R) group and ischemic postconditioning (IPTC) group. The left ventricular peak systolic pressure and its derivate (+/- dp/dt) were calculated; The amount of myocardium collagenous were determined; The vitality of superoxide dismutase (SOD) and content of malondialdehyde (MDA) of plasma were detected; The activity of myocardium MMP-2 was measured by Western blot and RT-PCR. RESULTS: As compared with I/R group, IPTC could lower the expression of MMP-2, ameliorate left ventricular function and increase the content of myocardium collagenous. In the meantime, the vitality of superoxide dismutase (SOD) of plasma were greatly enhanced and the content of malondialdehyde (MDA) of plasma were reduced in IFC group. CONCLUSION: Protective effect of IPIC on myocardium may be due to reduce free radical, lower expression of MMP-2 and protect myocardial interstitium. MMPs plays an important role in the myocardial protection provided by IPTC.


Assuntos
Pós-Condicionamento Isquêmico , Metaloproteinase 2 da Matriz/metabolismo , Traumatismo por Reperfusão Miocárdica/enzimologia , Animais , Colágeno/metabolismo , Malondialdeído/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
4.
Artigo em Chinês | MEDLINE | ID: mdl-25571634

RESUMO

OBJECTIVE: To investigate the effects of ischemic postconditioning (IPTC) on the changes of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) protein and mRNA levels in rat heart subjected to ischemia/reperfusion, and explore the mechanism by which IPTC protects myocardial interstitium following ischemic/reperfusion (I/R). METHODS: Twenty four healthy male SD rats were randomly divided into 3 groups (n = 8): sham control (SC) group, I/R group and IPTC group. The parameters of left ventricular function including left ventricular systolic pressure (LVSP) and its derivate (±dp/dt) were measured; the amount of myocardial collagen contents was determined by hydroxyproline quantification; the plasma activity of creatine kinase (CK) and lactate dehydrogenase (LDH) was detected; the protien levels of MMP-2 and TIMP-2 was measured by Western blot and the mRNA levels of MMP-2 and TIMP-2 was detected by real-time PCR. RESULTS: The myocardial collagen contents, left ventricular function and the protein and mRNA levels of TIMP-2 were significantly decreased in I/R group compared with those of SC group, wherease the activities of CK and LDH in the plasma and the protein and mRNA levels of MMP-2 were significantly enhanced in I/R group when compared to SC group. Compared with I/R group, the myocardial collagen contents, left ventricular function and the protein and mRNA levels of TIMP-2 were increased in IPTC group, the activities of CK and LDH in the plasma and the protein and mRNA level of MMP-2 were decreased in IPTC group. CONCLUSION: These findings indicate that IPTC has protective effects on myocardial interstitial after the myocardial ischemia/reperfusion injury, and IPTC may exert its cardioprotectve effect via inhibiting MMP-2 and enhancing TIMP-2 expression in cardiac muscle.


Assuntos
Pós-Condicionamento Isquêmico , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Função Ventricular Esquerda , Animais , Colágeno/metabolismo , Creatina Quinase/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Inibidor Tecidual de Metaloproteinase-2/metabolismo
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