RESUMEN
Aim To explore the effect of exogenous hydrogen sulfide ( H2 S ) on hypoxia/reoxygenation ( H/R) injury in glomerular mesangial cells and elucidate its relevant mechanism. Methods H/R induced mouse mesangial cell line ( SV40MES13 ) to establish cell damage model. Cell viability was detected by cell proliferation kit ( CCK8 ), the content of H
RESUMEN
OBJECTIVE@#To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood.@*METHODS@#Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B1 tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups.@*RESULTS@#From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group (P<0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group (P<0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group (P<0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group (P<0.05).@*CONCLUSION@#The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.
Asunto(s)
Humanos , Neuralgia Posherpética , Terapia por Acupuntura/métodos , Interleucina-10 , Interleucina-17 , Linfocitos T Reguladores , Ventosaterapia , Células Th17 , Herpes Zóster/terapia , Resultado del Tratamiento , ComprimidosRESUMEN
Aging contributes to age-related diseases such as cardiovascular diseases, diabetes, and Alzheimer’s disease, which are characterized by imbalance of protein homeostasis, accumulation of oxidative damage, stem cell failure, altered intercellular communication, chronic inflammation, and micro-ecological disorders. It is well known that hydrogen sulfide(H
RESUMEN
OBJECTIVE@#To investigate the recovery of protective effects of exogenous hydrogen sulfide (HS) on hypoxia post-conditioning in aged H9C2 cells and its mechanism.@*METHODS@#H9C2 cells (cardiomyocytes line) were treated with 30 μmol/L hydrogen peroxide (HO) for 2 hours, then cultured for 3 days in order to induce cellular aging. Aged H9C2 cells were randomly divided into 5 groups (=8):Control group (Control), hypoxia/reoxygenation group (H/R), H/R + NaHS group, hypoxia post-conditioning (PC) group, PC+NaHS group. H/R model:the cells were exposed to hypoxic culture medium (serum and sugar free medium, pH=6.8) for 3 hours and then cultured at normal condition for 6 hours. PC model:at the end of hypoxia for 3 hours, the cells were exposed to normoxic culture solution for 5 minutes, then the cells were placed in hypoxic solution for 5 minutes, the cycle above-mentioned was repeated 3 times and followed by reoxygenation for 6 hours. Advanced glycation end products (AGEs) content and caspase-3 activity were detected by ELISA. The cell viability was observed by cell counting kit-8 (CCK-8). The reactive oxygen species (ROS) levels were analyzed using 2, 7-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. The apoptotic rate was determined through Hoechst 33342 staining. The mRNA levels of relative gene expression were detected by real-time PCR.@*RESULTS@#Thirty μmol/L HO induced H9C2 cell senescence while did not lead to apoptosis. Compared with control group, cell viability was decreased, the apoptotic rate、levels of ROS and the mRNA of caspase-3, caspase-9 and Bcl-2 were increased in H/R and PC groups (<0.01). There were no differences in the above indexes between PC group and H/R group. Supplementation of NaHS increased cell viability and decreased apoptotic rate and oxidative stress. The effects of PC + NaHS on the above indexes were better than those of H/R+NaHS group.@*CONCLUSIONS@#Exogenous HS can restore the protective effect of PC on the aged H9C2 cells, and its mechanism is related to the inhibition of oxidative stress and apoptosis.
Asunto(s)
Humanos , Apoptosis , Hipoxia de la Célula , Supervivencia Celular , Peróxido de Hidrógeno , Miocitos Cardíacos , Especies Reactivas de OxígenoRESUMEN
<p><b>OBJECTIVE</b>To study the effects of low concentration dopamine(DA) on hydrogen peroxide-induced apoptosis in cultured rat cardiomyocytes as well as the possible molecular mechanisms.</p><p><b>METHODS</b>Cultured neonatal rat cardiomyocytes were randomly divided into the following groups: control group (control), hydrogen peroxide group (H2O2), pretreated with low concentration dopamine ( DA + H2O2), dopamine receptor l(DR1) antagonist group (DR1 + DA + H2O2), dopamine receptor 2(DR2) antagonist group (DR2 + DA + H2O2). The cell apoptosis was then assessed by MTT and flow cytometry. The cellular ultrastructure changes were observed by transmission electron micro- scope. The activity of lactate dehydrogenase(LDH )and superoxide dismutase (SOD) in cell medium was analyzed by colorimetry. The protein expressions of Cytochrone c, Caspase 3 and Caspase 9 were obtained by Western blot.</p><p><b>RESULTS</b>Compared with hydrogen peroxide group, low concentration dopamine(10 µmol/L) decreased the apoptosis rate and the expression of protein of apoptosis related protein, enhanced SOD activity, decreased LDH activity. DR1 antagonist SCH-23390 treatment inhibited dopamine induced cardiac protective effect. DR2 antagonist haloperido treatment had no changes compared with dopamine group.</p><p><b>CONCLUSION</b>Above findings indicate that low concentration dopanine inhibits apoptosis induced by hydrogen peroxide in neonatal rat cardiomyocytes, which is partly associated with the activation of DR1.</p>
Asunto(s)
Animales , Ratas , Apoptosis , Benzazepinas , Caspasa 3 , Metabolismo , Caspasa 9 , Metabolismo , Células Cultivadas , Dopamina , Farmacología , Peróxido de Hidrógeno , L-Lactato Deshidrogenasa , Metabolismo , Miocitos Cardíacos , Ratas Wistar , Receptores de Dopamina D1 , Metabolismo , Superóxido Dismutasa , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To observe the dynamic expression of calcium-sensing receptor(CaSR) in myocardium of diabetic rats.</p><p><b>METHODS</b>Thirty male Wistar rats were randomly divided into 3 groups including control, diabetic-4 week and diabetic-8 week groups(n = 10). The type 2 diabetes mellitus models were established by intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) after high-fat and high-sugar diet for one month. The cardiac morphology was observed by electron microscope. Western blot analyzed the expression of CaSR, phospholamban (PLN), a calcium handling regulator, and Ca+-ATPase(SERCA) in cardiac tissues.</p><p><b>RESULTS</b>Compared with control group, the expressions of CaSR and SERCA were decreased, while the expression of PLN was significantly increased in a time-dependent manner in diabetic groups. Meanwhile diabetic rats displayed abnormal cardiac structure.</p><p><b>CONCLUSION</b>These results indicate that the CaSR expression of myocardium is reduced in the progression of DCM, and its potential mechanism may be related to the imnaired intracellular calcium homeostasis.</p>
Asunto(s)
Animales , Masculino , Ratas , Proteínas de Unión al Calcio , Metabolismo , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Metabolismo , Progresión de la Enfermedad , Corazón , Miocardio , Metabolismo , Patología , Ratas Wistar , Receptores Sensibles al Calcio , Metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico , Metabolismo , EstreptozocinaRESUMEN
<p><b>OBJECTIVE</b>To study the effects of dopamin receptors-2 (DR2) on myocardial ischemic postconditioning and explore its underlying mechanisms.</p><p><b>METHODS</b>The myocardial ischemic postconditioning (PC) model was established in cultured primary rat neonatal cardiomyocytes which were then randomly assigned in the following groups: Nomial control group, Isehemia/reperfusion (L'R) group, PC (ischemic postconditioning) group, PC + Bro (Bromocriptine, a DB2 antagonist) group, PC + Hal (Haloperidol, a DB2 repressor) and PC + Hal + Bro groups. The lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cell medium were analyzed by colorunetry. The cell ultrastructure changes were observed by transmission electron microscope. The cell apoptosis was analyzed using flowcytometiy. The protein expression level of D112 and activity of p-p38 and p-JNK were detected by Western blot.</p><p><b>RESULTS</b>Compared with the nonnal control group, hR increased the protein expression level of DB2, enhanced LDH activity and MDA content, promoted cell injury and apoptosis, decreased SOD activity, up-regulated the activity of p-p38 and p-JNK. Compared with the hR group, although PC further increased the expression of DR2 protein, it decreased LDH activity and MDA content, cell injury and apoptosis, increased SOD activity, down-regulated activity of p-p38 and p-JNK. Bromocriptine treatment further enhanced PC-induced canlioprotective effect, yet Hal addition attenuated this enhancing effect exerted by bromocriptine.</p><p><b>CONCLUSION</b>The activation of DB2 is involved in the protective effect of ischemic postconditioning on myocardial ischemia/reperfusion injury through down-regulating the activity of p-p38 and p-JNK.</p>
Asunto(s)
Animales , Ratas , Apoptosis , Células Cultivadas , Poscondicionamiento Isquémico , Proteínas Quinasas JNK Activadas por Mitógenos , Metabolismo , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Patología , Ratas Wistar , Receptores de Dopamina D2 , Fisiología , Proteínas Quinasas p38 Activadas por Mitógenos , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of dopamine receptor (DR2) activation on hypoxia/reperfusion injury (HRI) in the neonatal rat cardiomyocytes, and to explore its mechanism.</p><p><b>METHODS</b>The hypoxia/reperfusion (H/R) injury model was established in primarily cultured neonatal rat cardiomyocytes, and randomly assigned: control, H/R, bromocriptine (Bro) and haloperidol (Hal) groups. The cell apoptosis was detected using inverted microscope, transmission electron microscope and flow cytometry (FCM). The lactate dehydrogenase(LDH) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cell medium were analyzed. The expression of mRNA and protein of caspase-3, caspase-8, caspase-9, Fas, Fas-L, Cyt C and Bcl-2 were detected by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>Compared with the control group, apoptosis rate, LDH activity, MDA content and the expression of pro-apoptotic factors and anti-apoptotic factors were increased, but SOD activity was decreased in H/R group. Compared with the H/R group, all index above-mentioned were down-regulated or reversed in Bro-group, and had no obvious differences in Hal-group.</p><p><b>CONCLUSION</b>The neonatal rat cardiomyocytes injury and apoptosis caused by hypoxia/reperfusion can be inhibited with DR2 activation, which mechanism is related to scavenging oxygen radical.</p>
Asunto(s)
Animales , Ratas , Animales Recién Nacidos , Apoptosis , Hipoxia de la Célula , Daño por Reperfusión Miocárdica , Metabolismo , Miocitos Cardíacos , Biología Celular , Metabolismo , Estrés Oxidativo , Ratas Wistar , Receptores de Dopamina D2 , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of hyperlipidemia and atherosclerosis on rat myocardial expression of calcium-sensing receptor and apoptosis.</p><p><b>METHODS</b>The rat atherosclerosis model was induced by intraperitoneal injection of VD(3) (6 x 10(5) U/kg) and high cholesterol diet. Wistar rats were divided into two groups: (1) Control group; (2) AS group (n = 12 each). The expressions of CaSR, Bcl-2, Bax and caspase-3 were analyzed by Western blot and RT-PCR. Apoptotic cells were observed by TUNEL assay. The morphological changes of abdominal aorta and cardiac tissues were observed under optical and electro microscopes. The activity of LDH, CK, SOD and the content of MDA were assayed with ultraviolet spectrophotometer. The level of cTnT was detected by electrochemical immunofluorescence.</p><p><b>RESULTS</b>Compared with control group, the activity of LDH and CK, the content of MDA and cTnT, the apoptosis index, the expression of CaSR, Bax and caspase-3 were significantly increased, but the SOD activity and Bcl-2 expression were significantly decreased, the myocardial ultrastructure injury was significantly aggravated in the AS group (all P < 0.05).</p><p><b>CONCLUSION</b>Hyperlipidemia and atherosclerosis can up-regulate myocardial calcium-sensing receptor expression, promote myocardial apoptosis, aggravate oxidative stress and myocardial ischemia.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratas , Apoptosis , Aterosclerosis , Metabolismo , Patología , Modelos Animales de Enfermedad , Hiperlipidemias , Metabolismo , Patología , Miocardio , Metabolismo , Estrés Oxidativo , Ratas Wistar , Receptores Sensibles al Calcio , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To observe the polyamines metabolism changes in rat cardiomyocytes underwent ischemia-reperfusion (I/R) injury.</p><p><b>METHODS</b>A branch of the descending left coronary artery was occluded to induce rat myocardial I/R injury (30 min ischemia followed by 2 h, 6 h, 12 h, and 24 h reperfusion). RT-PCR and Western blot were performed to detect the expression of spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC), the concentrations of polyamines were measured with high performance liquid chromatography in hearts with or without I/R.</p><p><b>RESULTS</b>The myocardial transcription and expression of SSAT and ODC were significantly upregulated. Compared with the sham group, ODC mRNA and SSAT mRNA respectively increased 3.1 fold and 3.8 fold and their proteins respectively increased 3.1 fold and 2.9 fold at 24 h of reperfusion (P < 0.01); the concentrations of spermidine, spermine and the total polyamine pool respectively decreased by 33.6%, 35.3% and 32.9% while putrescine concentration increased by 58.9% at 24 h of reperfusion (P < 0.01).</p><p><b>CONCLUSION</b>Our results suggest that ischemia-reperfusion in the heart may affect polyamine metabolism and the disturbance of polyamine metabolism might thus play a critical role in myocardial I/R injury in this model.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratas , Modelos Animales de Enfermedad , Daño por Reperfusión Miocárdica , Metabolismo , Miocardio , Metabolismo , Poliaminas , Metabolismo , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of artemisinin on the ischemia/reperfusion injury of the iisolated rat myocardium and to preliminarily study the possible mechanism.</p><p><b>METHOD</b>Fifty Wistar rats were randomly divided into 5 groups: a control group, an ischemia/reperfusion (I/R) group, and 3 artemisinin (AS) groups (10, 100, 1000 micromol x L(-1)), 10 rats in each group. Ischemia/reperfusion injury of the isolated rat myocardium was induced by a Langendorff system. The electrocardiogram, the cardiac functional parameters, coronary flow, and the activities of LDH (lactate dehydrogenase), CPK (creatine phosphokinase), SOD (superoxide dis-mutase) and the level of malondiadehyde (MDA) in myocardial tissue, and the myocardial ultrastructures were investigated.</p><p><b>RESULT</b>AS (10,100 micromol x L(-1)) could significantly improve the index of the myocardial function (+/- dp/dt(max), LVSP) after the ischemia/reperfusion, increase the coronary flow, decrease the leakage of LDH and CPK, and increase the SOD activity and decrease the MDA level in cardiac tissues, and alleviate the myocardial ultrastructure injury. But, AS (1000 micromo x L(-1)) did not have the above effects.</p><p><b>CONCLUSION</b>AS (10, 100 micromol x L(-1)) alleviate the myocardial ischemia/reperfusion injury in rats. The mechanism may be related to its functions of antioxidation and scavenging free radicals.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratas , Antioxidantes , Farmacología , Artemisia , Química , Artemisininas , Farmacología , Circulación Coronaria , Depuradores de Radicales Libres , Farmacología , Corazón , Daño por Reperfusión Miocárdica , Metabolismo , Patología , Miocardio , Patología , Plantas Medicinales , Química , Distribución Aleatoria , Ratas WistarRESUMEN
This study is to investigate the protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism. The cardiotoxicity was induced by intraperitoneal injection of adriamycin (ADR) at a single dose of 20 mg x kg(-1). Mice were randomly divided into 5 groups (n=20): normal control group, ADR 20 mg x kg(-1) group, quercetin (50, 100, and 200 mg x kg(-1) groups, intragastric administration, once a day, for 7 days before ADR administration). The health conditions, electrocardiogram, activity of iNOS, SOD and LDH, levels of NO and MDA in serum or tissue homogenate, the ultrastructure and the expression of p53 protein in cardiac tissue of mice were observed. Compared with the normal control group, ADR decreased the amplitude of ECG's R wave (P < 0.001), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH and iNOS, and levels of NO and MDA, decreased the activity of SOD, and increased the expression of p53 (P < 0.001). Compared with ADR 20 mg x kg(-1) group, the quercetin decreased the levels of LDH, iNOS, NO and MDA, increased the activity of SOD, restored the amplitude of R wave, decreased the incidence of arrhythmia and p53 expression (P < 0.001 , P < 0.01 or P < 0.05), and markedly reduced the myocardial ultrastructure injury. Quercetin had protective effect against adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, decreasing iNOS activity and inhibiting myocardial apoptosis.
Asunto(s)
Animales , Femenino , Masculino , Ratones , Apoptosis , Arritmias Cardíacas , Sangre , Metabolismo , Patología , Doxorrubicina , L-Lactato Deshidrogenasa , Metabolismo , Malondialdehído , Metabolismo , Miocardio , Metabolismo , Miocitos Cardíacos , Metabolismo , Óxido Nítrico , Sangre , Óxido Nítrico Sintasa de Tipo II , Sangre , Sustancias Protectoras , Farmacología , Quercetina , Farmacología , Distribución Aleatoria , Superóxido Dismutasa , Metabolismo , Proteína p53 Supresora de Tumor , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the relaxative characteristics of resveratrol on thoracic aortic artery in the rat and its mechanism.</p><p><b>METHOD</b>We perfused the isolated rings and observed the response of NA-induced artery contraction to resveratrol under the Ca2+-contained and Ca2+-free bath solutions. In the same way were the effect of reveratrol on the vascular smooth muscle observed by adding two different concentration of KCl (30 and 80 mmol x L(-1)), and the effect on the contraction of the vascular smooth muscle depending on the intracellular calcium and extracellular calcium were also observed by adding NA. We also observed the effect of resveratrol on the contraction of rings induced by NA in the presence of L-NNA and Glibenclamide.</p><p><b>RESULT</b>Resveratrol relaxed rat aorta rings precontracted by NA in a dose-dependent manner. The relaxant effect of resveratrol on the rat rings of endothelium-denuded group was reduced compared with that of endothelium-intact group; the relaxant effect of resveratrol on rat rings was higher under the condition of Ca2+-free bath solution than that under the condition of Ca2+-contained bath solution. Resveratrol had a repressive effect on the aorta's contraction induced by intracellular calcium, but had no effect induced by extracellular calcium. Resveratrol relaxed the contractions induced by KCl 30 mmol x L(-1) as well as KCl 80 mmol x L(-1), but the contraction curve of KCl 80 mmol x L(-1) was shifted upward significantly. In the L-NNA group, the relaxant effect was attenuated by (26.0 +/- 4.6) %; but there was no change in the group of Glibenclamide ( P > 0.05).</p><p><b>CONCLUSION</b>The results indicate that resveratrol relaxes vascular smooth muscle in an endothelium dependent manner. The mechanisms for this phenomenon seem to be related with promoting synthesis and release of NO, opening Ca2+ activated K+ channel (KCa channel) as well as the inhibition of Ca2+ influx and release of Ca2+ from intracellular stores.</p>