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1.
Front Oncol ; 12: 904471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814448

RESUMO

Objectives: To determine whether quantitative parameters derived from dual-energy computed tomography (DECT) were predictive of the aggressiveness of oral tongue squamous cell carcinoma (OTSCC) including the pathologic stages, histologic differentiation, lymph node status, and perineural invasion (PNI). Methods: Between August 2019 and March 2021, 93 patients (mean age, 54.6 ± 13.8 years; 66 men) with pathologically diagnosed OTSCC were enrolled in this prospective study. Preoperative DECT was performed and quantitative parameters (e.g., slope of the spectral Hounsfield unit curve [λHu], normalized iodine concentration [nIC], normalized effective atomic number [nZeff], and normalized electron density [nRho]) were measured on arterial phase (AP) and venous phase (VP) DECT imaging. Quantitative parameters from DECT were compared between patients with different pathologic stages, histologic differentiation, lymph node statuses, and perineural invasion statuses. Logistic regression analysis was utilized to assess independent parameters and the diagnostic performance was analyzed by the receiver operating characteristic curves (ROC). Results: λHu and nIC in AP and λHu, nZeff, and nIC in VP were significantly lower in stage III-IV lesions than in stage I-II lesions (p < 0.001 to 0.024). λHu in VP was an independent predictor of tumor stage with an odds ratio (OR) of 0.29, and area under the curve (AUC) of 0.80. λHu and nIC were higher in well-differentiated lesions than in poorly differentiated lesions (p < 0.001 to 0.021). The nIC in VP was an independent predictor of histologic differentiation with OR of 0.31, and AUC of 0.78. λHu and nIC in VP were lower in OTSCCs with lymph node metastasis than those without metastasis (p < 0.001 to 0.005). λHu in VP was the independent predictor of lymph node status with OR of 0.42, and AUC of 0.74. No significant difference was found between OTSCCs without PNI and those with PNI in terms of the quantitative DECT parameters. Conclusion: DECT can be a complementary means for the preoperative prediction of the aggressiveness of OTSCC.

2.
Histol Histopathol ; 34(3): 223-231, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30255492

RESUMO

Prompt myocardial reperfusion during acute myocardial infarction by fibrinolytic therapy, percutaneous coronary intervention, or coronary artery bypass grafting limits the affected area and improves prognosis. However, reperfusion itself can cause cardiomyocyte damage and decrease treatment efficacy. No treatments that effectively prevent myocardial ischemia/reperfusion (I/R) injury are currently available, and are therefore the focus of ongoing research. Salvianolic acid A (SAA), the active ingredient of the traditional Chinese herbal remedy Salvia miltiorrhiza, has anti-thrombotic activity, anti-inflammatory, and anti-cancer activity; regulates blood lipids and provides hepatic and neural protection. Recent studies demonstrated that SAA inhibits cardiomyocyte apoptosis in response to I/R by the PI3K/Akt, GSK-3ß, JNK, and ERK1/2 pathways, and by JNK-ERK1/2 crosstalk. The mechanisms for SAA attenuating cardiomyocytes apoptosis during I/R injury through the P38 MAPK, caspase, JAK/STAT, NF-κB and LOX-1 signaling pathways need further illustration. There may be potential crosstalks between PI3K/Akt and JNK, and Akt/GSK-3ß and ERK1/2 in the process of SAA against I/R-incuced cardiomyocytes apoptosis. This review summarizes the recent evidence of the anti-apoptotic effects and mechanisms of SAA against myocardial I/R injury and discusses the basis of potential clinical applications of SAA.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Lactatos/farmacologia , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos/efeitos dos fármacos , Animais , Humanos
3.
Chin J Integr Med ; 23(7): 518-527, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26956461

RESUMO

OBJECTIVE: To investigate the antioxidative effect and mechanism of luteolin on rat cardiomyocytes and isolated hearts followed by simulated ischemia/reperfusion (SI/R) injury. METHODS: The left ventricular cardiomyocytes and the isolated hearts from adult rats were subjected to SI/R injury. The experiment groups included control, SI/R, luteolin + SI/R (Lut + SI/R), vitamin E (Vit E) + SI/R, and LY294002 + luteolin + SI/R (LY + Lut + SI/R) groups. Cell viability, shortening amplitude, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity, the production of reactive oxygen species (ROS) and malondialdehyde (MDA), expression levels of Akt, phosphorylated Akt, NOX2 (gp91phox), NOX2 mRNA, mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38MAPK were all measured after 3-h simulated ischemia and 2-h simulated reperfusion procedure in cardiomyocytes. Vit E was used as a standard control. The contractile function of isolated hearts was further observed after they were subjected to 30-min global ischemia and 120-min reperfusion. RESULTS: Pretreatment with 8-µmol/L luteolin substantially increased cell viability and shortening amplitude, while reducing evidence of oxidative stress-induced damage in the cells. In addition, the expression of NOX2, NOX2 mRNA and phosphorylation of p38MAPK were all downregulated. Furthermore, pretreatment with 40-µmol/L luteolin improved the recovery of myocardial contractile function following SI/R-induced injury, and luteolin markedly increased phosphorylation of Akt. However, all of the above effects were partially inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. CONCLUSIONS: Luteolin prevents SI/R-induced myocardial damage by reducing oxidative stress-induced injury in isolated rat hearts and cardiomyocytes, and the cardioprotection induced by luteolin was partially mediated by the PI3K/Akt pathway.


Assuntos
Antioxidantes/uso terapêutico , Luteolina/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/patologia , Miócitos Cardíacos/patologia , Perfusão , Animais , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , L-Lactato Desidrogenase/metabolismo , Luteolina/farmacologia , Masculino , Malondialdeído/metabolismo , Modelos Biológicos , Contração Miocárdica/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Curr Pharm Biotechnol ; 17(3): 283-90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26873077

RESUMO

We discuss the role of Salvianolic acid A(SAA), one of the main effective components in Salvia Miltiorrhiza (known as 'Danshen' in traditional Chinese medicine), in apoptotic factors, the production of oxidative products, and the expression of Akt and NF-κB in angiotensin II (Ang II)-mediated murine macrophages. In the present study, Ang II was added to mice abdominal macrophages with or without addition of SAA. After cell identification, apoptosis was measured by DNA strand break level with TdT-mediated dUTP nick-end labeling (TUNEL) staining, and the expression of Bcl-2 and Bax. Intracellular concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. Western blotting determined the expression of Akt, p-Akt, NF-κB and p-NF-κB. Ly294002 (the inhibitor of PI3K) was used to determine the mechanism of SAA. Ang II (1 µM) significantly increased the number of TUNEL-positive cells and Bax expression, but reduced Bcl-2 expression. These effects were antagonized when the cells were pretreated with SAA. SAA decreased MDA, but increased SOD in the cell lysis solution treated with Ang II. It markedly reduced the level of p-NF-κB, as also p-Akt, which was partly blocked by Ly294002. SAA prevents Ang IIinduced apoptosis, oxidative stress and related protein expression in the macrophages. It also inhibits the activation of Akt.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Lactatos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Angiotensina II/farmacologia , Animais , Células Cultivadas , Ativação Enzimática , Feminino , Marcação In Situ das Extremidades Cortadas , Macrófagos Peritoneais/metabolismo , Malondialdeído/metabolismo , Camundongos , Superóxido Dismutase/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-26681967

RESUMO

The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications.

6.
Artigo em Inglês | MEDLINE | ID: mdl-26347796

RESUMO

Luteolin is a naturally occurring flavonoid found in many plants that possesses cardioprotective properties. The purpose of this study was to elucidate the effect of luteolin on vascular smooth muscle cells (VSMCs) proliferation and migration induced by Angiotensin II (Ang II) and to investigate the mechanism(s) of action of this compound. Rat VSMCs were cultured in vitro, and the proliferation and migration of these cells following Ang II stimulation were monitored. Different doses of luteolin were added to VSMC cultures, and the proliferation and migration rate were observed by MTT and Transwell chamber assays, respectively. In addition, the expressions of p-Akt (308), p-Akt (473), and proliferative cell nuclear antigen (PCNA) in VSMCs were monitored by Western blotting. This study demonstrated that luteolin has an inhibitory effect on Ang II-induced VSMC proliferation and migration. Further, the levels of p-Akt (308), p-Akt (473), and PCNA were reduced in VSMCs treated with both Ang II and luteolin compared to VSMCs treated with only Ang II. These findings strongly suggest that luteolin inhibits Ang II-stimulated proliferation and migration of VSMCs, which is partially due to downregulation of the Akt signaling pathway.

7.
Molecules ; 18(7): 8083-94, 2013 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-23839113

RESUMO

Luteolin (Lut) is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. The purposes of this study were to observe the inhibition of lipopolysaccharide (LPS)-induced inflammatory responses in bone marrow macrophages (BMM) by Lut, and to examine whether this inhibition involves p38/MK2/TTP-mediated mRNA stability. Lut suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner according to enzyme-linked immunosorbent assay (ELISA) analysis. Lut also shortened the half-lives of the TNF-α and IL-6 mRNAs according to real-time PCR analysis. Western blots were performed to assess the activation of p38 and MK2 as well as the expression of TTP. The results indicated that Lut inhibited p38 and MK2 phosphorylation while promoting TTP expression. These results suggest that the anti-inflammatory effects of Lut are partially mediated through p38/MK2/TTP-regulated mRNA stability.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Luteolina/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Tristetraprolina/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios não Esteroides/química , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Fêmur , Interleucina-6/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/genética , Luteolina/química , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Tíbia , Tristetraprolina/genética , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/genética
8.
Nutrients ; 5(5): 1648-59, 2013 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-23686014

RESUMO

Atherosclerosis (AS) is a complicated progress, involving many types of cells. Although the exact mechanisms of progression of atherosclerosis are uncertain, the balance of vascular smooth muscle cells (VSMCs) proliferation and apoptosis appears to play a pivotal role in the pathogenesis and progression of atherosclerosis, and much discussion has been undertaken to elucidate the detailed mechanisms, relevant gene expression and transduction pathways. Drug treatment has focused on ameliorating atherosclerosis. Some researchers have indicated that inhibiting VSMCs proliferation is involved in attenuating atherosclerosis. Luteolin is a kind of flavonoids naturally occurring in many plants and possesses beneficial effects on cardiovascular diseases. Luteolin can reduce VSMCs' proliferation and migration and this reduction is stimulated by several factors. The aim of this review is to summarize the existing inhibitory effects and mechanisms of luteolin on proliferation and migration of VSMCs, and consider whether luteolin may be a potential candidate for preventing and treating atherosclerosis.


Assuntos
Aterosclerose/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Luteolina/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Humanos , Músculo Liso Vascular/citologia
9.
PLoS One ; 8(12): e82957, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24386130

RESUMO

Luteolin has long been used in traditional Chinese medicine for treatment of various diseases. Recent studies have suggested that administration of luteolin yields cardioprotective effects during ischemia/reperfusion (I/R) in rats. However, the precise mechanisms of this action remain unclear. The aim of this study is to confirm that luteolin-mediated extracellular signal regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways are responsible for their cardioprotective effects during I/R. Wistar rats were divided into the following groups: (i) DMSO group (DMSO); (ii) I/R group (I/R); (iii) luteolin+I/R group (Lut+I/R); (iv) ERK1/2 inhibitor PD98059+I/R group (PD+I/R); (v) PD98059+luteolin+I/R group (PD+Lut+I/R); and (vi) JNK inhibitor SP600125+I/R group (SP+I/R). The following properties were measured: contractile function of isolated heart and cardiomyocytes; infarct size; the release of lactate dehydrogenase (LDH); the percentage of apoptotic cells; the expression levels of Bcl-2 and Bax; and phosphorylation status of ERK1/2, JNK, type 1 protein phosphatase (PP1a), phospholamban (PLB) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a). Our data showed that pretreatment with luteolin or SP600125 significantly improved the contraction of the isolated heart and cardiomyocytes, reduced infarct size and LDH activity, decreased the rate of apoptosis and increased the Bcl-2/Bax ratio. However, pretreatment with PD98059 alone before I/R had no effect on the above indexes. Further, these consequences of luteolin pretreatment were abrogated by co-administration of PD98059. We also found that pretreatment with PD98059 caused a significant increase in JNK expression, and SP600125 could cause ERK1/2 activation during I/R. In addition, we are the first to demonstrate that luteolin affects PP1a expression, which results in the up-regulation of the PLB, thereby relieving its inhibition of SERCA2a. These results showed that luteolin improves cardiomyocyte contractile function after I/R injury by an ERK1/2-PP1a-PLB-SERCA2a-mediated mechanism independent of JNK signaling pathway.


Assuntos
Luteolina/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Ratos , Traumatismo por Reperfusão/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/fisiologia
10.
Nutrients ; 4(12): 2008-19, 2012 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-23235403

RESUMO

Myocardial ischemia often results in damaged heart structure and function, which can be restored through ischemia/reperfusion (I/R) in most cases. However, I/R can exacerbate myocardial ischemia reperfusion injury (IRI). Luteolin, a widely distributed flavonoid, a member of a group of naturally occurring polyphenolic compounds found in many fruits, vegetables and medicinal herbs, has been reported to exhibit anti-inflammatory, antioxidant and anti-carcinogenic activities. In recent years, luteolin has been shown to play an important role in the cardioprotection of IRI. However, its role and mechanism in cardioprotection against IRI has not been clearly elucidated with respect to the apoptosis pathway. The purpose of this paper is to review luteolin's anti-apoptotic role and mechanism following I/R in rats, and indicate luteolin as a potential candidate for preventing and treating cardiovascular diseases.


Assuntos
Apoptose/efeitos dos fármacos , Luteolina/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Luteolina/farmacologia , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos
11.
J Pharm Pharmacol ; 64(4): 597-603, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22420665

RESUMO

OBJECTIVES: Luteolin is a naturally occurring flavonoid found in many vegetables, fruits and medicinal plants. The migration and proliferation of vascular smooth muscle cells (VSMCs) are the critical pathological processes in various cardiovascular diseases, such as atherosclerosis. In this study, we investigated the effect of luteolin and its latent mechanism on the proliferation and migration of VSMCs stimulated by hydrogen peroxide (H(2) O(2) ). METHODS: VSMC proliferation and cell viability was assayed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) method or by cell counting, and H(2) O(2) -elicited migration of VSMCs was measured using a transwell migration assay. The phosphorylation levels of Src, 3-phosphoinositide-dependent kinase 1 (PDK1) and Akt (protein kinase B) were analysed by immunoblotting. KEY FINDINGS: This study demonstrated that luteolin showed a particularly inhibitory effect on H(2) O(2) -elicited VSMC proliferation and migration. In previous research, we originally explored the function of luteolin in blocking H(2) O(2) -triggered Src and Akt signalling pathways. The activation of Src, PDK1, Akt (308), Akt (473) in the luteolin-treated group was significantly lower than that seen in the H(2) O(2) group. CONCLUSIONS: These findings strongly suggested that luteolin suppresses H(2) O(2) -directed migration and proliferation in VSMCs partially due to down-regulation of the Akt and Src signalling pathways, which are important participants in the processes of migration and proliferation of VSMCs.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Luteolina/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Regulação para Baixo/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/farmacologia , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Quinases da Família src/metabolismo
12.
J Endocrinol ; 212(1): 61-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21965546

RESUMO

After menopause, the development of cardiovascular disease (CVD) is due not only to estrogen decline but also to androgen decline. This study examined the effects of either estradiol (E(2)) or testosterone replacement alone or E(2)-testosterone combination on isolated myocytes in ovariectomized (Ovx) rats subjected to ischemia/reperfusion (I/R). Furthermore, we determined whether the effects are associated with ß(2)-adrenoceptor (ß(2)-AR). Five groups of adult female Sprague-Dawley rats were used: Sham operation (Sham) rats, bilateral Ovx rats, Ovx rats with E(2) 40 µg/kg per day (Ovx+E), Ovx rats with testosterone 150 µg/kg per day (Ovx+T), and Ovx rats with E(2) 40 µg/kg per day+testosterone 150 µg/kg per day (Ovx+E/T). We determined the lactate dehydrogenase (LDH) release, percentage of rod-shaped cells and apoptosis of ventricular myocytes from rats of all groups subjected to I/R. Then, we determined the above indices and contractile function with or without a selective ß(2)-AR antagonist ICI 118 551. We also determined the expression of ß(2)-AR. Our data show that either E(2) or testosterone replacement alone or E(2) and testosterone in combination decreased the LDH release, increased the percentage of rod-shaped cells, reduced apoptotic cells (%), and combination treatment appeared to be more effective than either E(2) or testosterone replacement alone. ICI 118 551 abolished the effects of the three. Combination supplementation also enhanced the expression of ß(2)-AR. We concluded that in Ovx rats, testosterone enhances E(2)'s cardioprotection, while E(2) and testosterone in combination was more effective and the protective effects may be associated with ß(2)-AR. The study highlights the potential therapeutic application for CVD in postmenopausal women.


Assuntos
Estradiol/uso terapêutico , Terapia de Reposição Hormonal , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Receptores Adrenérgicos beta 2/metabolismo , Testosterona/uso terapêutico , Antagonistas Adrenérgicos beta , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Estradiol/farmacologia , Feminino , L-Lactato Desidrogenase/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Ovariectomia , Propanolaminas , Ratos , Ratos Sprague-Dawley , Testosterona/farmacologia , Regulação para Cima
13.
J Cardiovasc Pharmacol ; 58(5): 535-42, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21795988

RESUMO

Salvianolic acid A (Sal A), the water-soluble component from the root of the Salvia miltiorrhiza plant, possesses antioxidant, antiproliferative, and antiplatelet properties. However, whether it plays a role in the protection against ischemia-reperfusion (I/R) injury in rat hearts has yet to be elucidated. In the present study, we tested cell viability, shortening amplitude, necrosis, apoptosis, and the expression levels of Akt, phosphorylated Akt, Bcl-2, Bax, and caspase-3 after 3-hour simulated ischemia and 2- or 6-hour simulated reperfusion in cardiomyocytes. We further observed the contractile function and infarct size in isolated hearts after they were subjected to global 30-minute ischemia and 120-minute reperfusion. Pretreatment with Sal A markedly increased cell viability and shortening amplitude while reducing evidence of necrosis and apoptosis in the cells. In addition, the expression of Bcl-2 was upregulated and Bax was downregulated, thereby increasing the Bcl-2/Bax ratio. Sal A inhibited the activation of caspase-3 as well. The results also showed that Sal A significantly increased phosphorylation of Akt and that this phosphorylation can be partially inhibited by phosphoinositide 3-kinase/Akt inhibitor. Furthermore, Sal A improved I/R-induced myocardial contractile function and reduced infarct size. In summary, our results showed that Sal A prevents I/R-induced myocardial damage by reducing necrosis and apoptosis in isolated rat hearts and cardiomyocytes.


Assuntos
Ácidos Cafeicos/uso terapêutico , Cardiotônicos/uso terapêutico , Coração/efeitos dos fármacos , Lactatos/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Cardiotônicos/farmacologia , Caspase 3/metabolismo , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Lactatos/farmacologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Necrose/patologia , Necrose/prevenção & controle , Perfusão , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle , Proteína X Associada a bcl-2/metabolismo
14.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 27(8): 692-5, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17879530

RESUMO

OBJECTIVE: To investigate the clinical significance of matrix metalloproteinase-9 (MMP-9) and tissue factor (TF) secreted by cultured monocyte-derived macrophages (HMDM) from patients with coronary heart disease (CHD) in vitro, and to evaluate the intervenient effect of puerarin (Pur) on them. METHODS: A total of 40 patients were enrolled, including 12 patients with acute myocardial infarction (AMI), 16 patients with unstable angina pectoris (UAP), 12 patients with stable angina pectoris (SAP). Besides, 8 healthy subjects with normal coronary arteriograph were set as controls. Monocytes acquired from their peripheral blood were incubated for 48 h and induced to differentiate into macrophages by phorbolester 12-myristate 13-acetate (PMA), the contents of MMP-9 and TF in supernatant were assayed, and the relationship of them with patients' age, risk factors of CHD and coronary artery lesion scores were analyzed. HMDMs randomly from selected 12 patients with acute coronary syndrome (ACS) were arranged for observing the intervenient effects of different concentrations of Pur on the levels and activity of MMP-9 and TF. RESULTS: The levels of MMP-9 and TF in UAP and AMI patients were significantly higher than those in SAP patients and healthy subjects (P < 0.01), but no statistical correlation was found between levels of MMP-9 and TF with different CHD risk factors, as well as patients' age and coronary artery lesion scores. The levels and activity of MMP-9 and TF in the 12 ACS patients were significantly decreased in a dose-dependent manner after Pur intervention when compared with the controt group. CONCLUSION: The levels of MMP-9 and TF secreted in vitro by HMDM from CHD patients could be taken as indexes for evaluating patient's condition of ACS. Pur can inhibit the expression and the activity of MMP-9 and TF secreted by HMDM, stabilize the plaque and improve the vulnerability of blood to certain extent.


Assuntos
Doença das Coronárias/tratamento farmacológico , Isoflavonas/uso terapêutico , Macrófagos/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Tromboplastina/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Doença das Coronárias/metabolismo , Feminino , Humanos , Isoflavonas/farmacologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Monócitos/patologia , Vasodilatadores/uso terapêutico
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