RESUMO
OBJECTIVE: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. METHODS: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. RESULTS: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). CONCLUSION: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.
Assuntos
Flavonoides/farmacologia , Infarto do Miocárdio/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Creatina Quinase Forma MB/sangue , Ensaio de Imunoadsorção Enzimática , Epoprostenol/sangue , Genes bcl-2 , Hemodinâmica/efeitos dos fármacos , L-Lactato Desidrogenase/sangue , Malondialdeído/análise , Distribuição Aleatória , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Superóxido Dismutase/análise , Tromboxano A2/sangue , Resultado do Tratamento , Proteína X Associada a bcl-2/análiseRESUMO
PURPOSE: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. METHODS: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). RESULTS: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. CONCLUSION: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.
Assuntos
Broncodilatadores/farmacologia , Endotelina-1/sangue , Epoprostenol/sangue , Óxido Nítrico/farmacologia , Embolia Pulmonar/sangue , Embolia Pulmonar/tratamento farmacológico , Tromboxano A2/sangue , Troponina I/sangue , Doença Aguda , Administração por Inalação , Animais , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Masculino , Embolia Pulmonar/patologia , Coelhos , Distribuição Aleatória , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.
Assuntos
Animais , Flavonoides/farmacologia , Substâncias Protetoras/farmacologia , Infarto do Miocárdio/prevenção & controle , Valores de Referência , Superóxido Dismutase/análise , Tromboxano A2/sangue , Ensaio de Imunoadsorção Enzimática , Distribuição Aleatória , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão , Epoprostenol/sangue , Resultado do Tratamento , Ratos Sprague-Dawley , Genes bcl-2 , Creatina Quinase Forma MB/sangue , Proteína X Associada a bcl-2/análise , Hemodinâmica/efeitos dos fármacos , L-Lactato Desidrogenase/sangue , Malondialdeído/análiseRESUMO
Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.
Assuntos
Animais , Masculino , Feminino , Coelhos , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/sangue , Tromboxano A2/sangue , Broncodilatadores/farmacologia , Epoprostenol/sangue , Endotelina-1/sangue , Troponina I/sangue , Óxido Nítrico/farmacologia , Embolia Pulmonar/patologia , Valores de Referência , Fatores de Tempo , Administração por Inalação , Ensaio de Imunoadsorção Enzimática , Distribuição Aleatória , Regulação para Baixo , Doença Aguda , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
The aim of this study was to investigate the correlation between circulating endothelial progenitor cell (EPC) levels and plasma prostacyclin (PGI2) concentrations in pulmonary hypertension (PH) rat models. Monocrotaline was used to induce PH, and the number of CD34/Flk-1-double-positive mononuclear cells in peripheral CD45-negative blood was counted by flow cytometry, which reflected EPC circulation. The Greiss method was used to detect the plasma PGI2 concentration. Simple linear regression analysis was used to analyze the relationship between EPC and PGI2. Furthermore, the expressions of cycled EPC, CD34, and Flk-1 were detected under in vitro culture conditions. The mean circulating EPC level in the PH model group (0.013 ± 0.004%) was significantly lower (P < 0.01) than that in the control group (0.036 ± 0.009%). The concentration of plasma PGI2 also significantly decreased (24.36 ± 2.08 vs 58.34 ± 3.31 µM; P < 0.01). There was a positive correlation between EPC and PGI2 (r = 0.870, P < 0.05). Under in vitro culture conditions, the EPC number and the CD34 and Flk-1 expression levels in the PH model group were significantly lower than those in the control group. Together, these results suggest that the occurrence of PH may be associated with decreased plasma PGI2 concentrations, resulting in the reduction of circulating EPC.
Assuntos
Células-Tronco Adultas/metabolismo , Células Endoteliais/metabolismo , Epoprostenol/sangue , Hipertensão Pulmonar/sangue , Animais , Antígenos CD34/genética , Antígenos CD34/metabolismo , Células Cultivadas , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Leucócitos Mononucleares/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Activation of TLRs (Toll-like receptors) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of CVDs (cardio-vascular diseases). Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study, we hypothesize that inhibition of TLR4 decreases BP (blood pressure) and improves vascular contractility in resistance arteries from SHR (spontaneously hypertensive rats). TLR4 protein expression in mesenteric resistance arteries was higher in 15-week-old SHR than in age-matched Wistar controls or in 5-week-old SHR. To decrease the activation of TLR4, 15-week-old SHR and Wistar rats were treated with anti-TLR4 (anti-TLR4 antibody) or non-specific IgG control antibody for 15 days (1 µg per day, intraperitoneal). Treatment with anti-TLR4 decreased MAP (mean arterial pressure) as well as TLR4 protein expression in mesenteric resistance arteries and IL-6 (interleukin 6) serum levels from SHR when compared with SHR treated with IgG. No changes in these parameters were found in treated Wistar control rats. Mesenteric resistance arteries from anti-TLR4-treated SHR exhibited decreased maximal contractile response to NA (noradrenaline) compared with IgG-treated SHR. Inhibition of COX (cyclo-oxygenase)-1 and COX-2, enzymes related to inflammatory pathways, decreased NA responses only in mesenteric resistance arteries of SHR treated with IgG. COX-2 expression and TXA2 (thromboxane A2) release were decreased in SHR treated with anti-TLR4 compared with IgG-treated SHR. Our results suggest that TLR4 activation contributes to increased BP, low-grade inflammation and plays a role in the augmented vascular contractility displayed by SHR.
Assuntos
Pressão Sanguínea , Hipertensão/fisiopatologia , Receptor 4 Toll-Like/fisiologia , Vasoconstrição , Animais , Artérias/fisiopatologia , Ciclo-Oxigenase 1/sangue , Ciclo-Oxigenase 2/sangue , Epoprostenol/sangue , Regulação da Expressão Gênica , Hemodinâmica/efeitos dos fármacos , Hipertensão/genética , Imunidade Inata , Interleucina-6/sangue , Masculino , Proteínas de Membrana/sangue , Artérias Mesentéricas/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Tromboxano A2/sangue , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/sangueRESUMO
Trypanosoma cruzi induces inflammatory reactions in several tissues. The production of prostaglandin F2alpha, 6-keto-prostaglandin F1alpha and thromboxane B2, known to regulate the immune response and to participate in inflammatory reactions, was studied in mice experimentally infected with T. cruzi. The generation of nitric oxide (NO), which could be regulated by cyclooxygenase metabolites, was also evaluated. In the acute infection the extension of inflammatory infiltrates in skeletal muscle as well as the circulating levels of cyclooxygenase metabolites and NO were higher in resistant C3H mice than in susceptible BALB/c mice. In addition, the spontaneous release of NO by spleen cells increased earlier in the C3H mouse strain. In the chronic infections, the tissue inflammatory reaction was still prominent in both groups of mice, but a moderate increase of thromboxane B2 concentration and in NO released by spleen cells was observed only in C3H mice. This comparative study shows that these mediators could be mainly related to protective mechanisms in the acute phase, but seem not to be involved in its maintenance in the chronic T. cruzi infections.
Assuntos
Doença de Chagas/sangue , Dinoprostona/sangue , Epoprostenol/sangue , Prostaglandina-Endoperóxido Sintases/metabolismo , Tromboxano A2/sangue , Doença Aguda , Animais , Doença de Chagas/complicações , Doença de Chagas/metabolismo , Doença Crônica , Suscetibilidade a Doenças , Inflamação/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Músculo Esquelético/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Especificidade da Espécie , Baço/metabolismo , Baço/patologia , Tromboxano B2/metabolismoRESUMO
D-003 is a mixture of very high molecular weight aliphatic acids purified from sugar cane wax showing cholesterol-lowering and antiplatelet effects proven in experimental and clinical studies. Experimental evidence indicates that inhibition of platelet aggregation induced by D-003 is associated with a reduction of thromboxane B2 (TxB2) and an increase of prostacyclin (Pgl2) serum levels. This double-blinded, randomized, placebo-controlled study was undertaken to investigate whether D-003 (20 mg/day) modifies serum levels of TxB2 and Pgl2 and inhibits platelet aggregation in human healthy volunteers. Thirty-one subjects were randomized to placebo or D-003 at 20 mg/day for 14 days. Serum levels of TxB2 and Pgl2 and platelet aggregation to arachidonic acid (AA) (1.75 mM) and collagen (1 microg/ml) were assessed. D-003 (20 mg/day) significantly reduced (p < 0.001) TxB2by 36.4% and increased Pgl2 serum levels by 31% compared with baseline, and these changes were different from placebo. As expected, D-003 significantly inhibited (p < 0.001) platelet aggregation to AA (81.9-65.6%) and to collagen (75.3-62.3%). No subject withdrew from the study. No drug-related disturbances were observed. We conclude that D-003 at 20 mg/day for 14 days significantly inhibited platelet aggregation to AA and collagen and reduced TxB2 and increased Pgl2 serum levels. These results are consistent with those observed in experimental models, indicating that the antiplatelet effect of D-003 is associated with the observed changes on the levels of AA metabolites. Further studies, however, should explore the mechanism involved in this action in greater depth.
Assuntos
Ácidos Araquidônicos/sangue , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Saccharum/química , Ceras/isolamento & purificação , Adulto , Ácidos Araquidônicos/antagonistas & inibidores , Astenia/induzido quimicamente , Colágeno Tipo I/antagonistas & inibidores , Colágeno Tipo I/farmacologia , Método Duplo-Cego , Esquema de Medicação , Epoprostenol/sangue , Ácidos Graxos/efeitos adversos , Ácidos Graxos/química , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Agregação Plaquetária/fisiologia , Comprimidos , Tromboxano B2/antagonistas & inibidores , Tromboxano B2/sangue , Fatores de Tempo , Ceras/químicaRESUMO
D-003 is a natural mixture of long chain aliphatic acids isolated and purified from sugar cane wax. It possesses antiplatelet and antithrombotic effects as well as decreases plasma and serum levels of thromboxane B(2) (TxB(2)), meanwhile significantly and markedly raises prostacyclin (PgI(2)) levels in rats. This study was undertaken to investigate the effects of D-003 on spinal cord injury in rabbits. New Zealand rabbits were treated during 10 days with D-003 (25 and 200 mg kg(-1)) and ASA (2 mg kg(-1)) before spinal cord ischemia. Animals were subjected to 20 min of aortic occlusion and 24h of reperfusion. Clinical symptoms and histopathological changes of spinal cord were observed. The PgI(2) levels in thoracic aorta were quantified by bioassay. D-003 (25 and 200 mg kg(-1)) significantly increased the mean scores reached 4h after reperfusion, although no dose relation was observed. Twenty-four hours after reperfusion, no deaths occurred in both sham and D-003 treated groups, meanwhile in positive controls and ASA the mortality rate was 38.5% and 7.69% respectively. In addition, 100% of sham, 69% and 77% of rabbits treated with D-003 at 25 and 200 mg kg(-1), respectively, did not show histopathological changes. By the contrary, 100% of positive control animals showed severe damage and ASA-treated rabbits showed only a partial protection. Animals treated with both doses of D-003 showed PgI(2) levels significantly larger than those of positive and negative controls, an effect dose-related, while ASA 2 mg kg(-1) did not change PgI(2) values. The increase of PgI(2) levels achieved in the D-003 treated animals could be an important mechanism in the protection against the spinal cord ischemia.
Assuntos
Ácidos Graxos/farmacologia , Substâncias Protetoras/farmacologia , Isquemia do Cordão Espinal/tratamento farmacológico , Isquemia do Cordão Espinal/prevenção & controle , Animais , Aorta/efeitos dos fármacos , Epoprostenol/sangue , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Coelhos , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Isquemia do Cordão Espinal/patologia , Taxa de SobrevidaRESUMO
The interaction between angiotensin-(1-7) [Ang-(1-7)] and bradykinin (BK) was studied in the isolated mesenteric arteriolar bed of control and diabetic rats perfused with either 5.5 or 22 mM of glucose. Prostanoids release after the administration of BK, Ang-(1-7) and Ang-(1-7)+BK was also studied. In control and diabetic preparations perfused with Krebs Henseleit solution with 5.5mM of glucose, Ang-(1-7) potentiates BK-induced vasodilation. On the other hand, the potentiating effect disappeared in control and diabetic preparations perfused with 22 mM of glucose. Prostaglandin F(2alpha) (PGF(2alpha)) release induced by BK and Ang-(1-7)+BK was increased in perfusates of diabetic preparations containing 22 mM of glucose. The release of thromboxane A(2) (TXA(2)) (measured as TXB(2)) or prostaglandin I(2) (PGI(2)) (measured as 6-keto-PGF(1alpha)) did not differ in control and diabetic preparations perfused with 5.5 and 22 mM of glucose. Our data allow us to suggest that hyperglycemia may be involved in the lack of potentiation in control and diabetic preparations; increase in PGF(2alpha) release, but not other cyclooxygenase products, may explain the absence of potentiation in diabetic preparations.