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Objective@#To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF.@*Methods@#We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis.@*Results@#(1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation.@*Conclusions@#The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.
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Objective@#To investigate the effect and related mechanism of homocysteine (Hcy) on calcium overload in neonatal rat atrial cells (NRICs).@*Methods@#NRICs were assigned to 9 groups after culture for 3 days: (1) control group; (2) Hcy group (0, 50, 100, 200, 500 μmol/L for 48 hours); (3) antioxidant group (NAC, 10 μmol/L for 24 hours); (4) Hcy+NAC group (500 μmol/L Hcy for 48 hours, then treated with 10 μmol/L NAC for 24 hours); (5) calcium/calmodulin dependent protein kinase Ⅱδ (CaMKⅡδ) inhibitor group (KN-93, 3 μmol/L KN-93 for 5 hours); (6) specific sodium current inhibitor group (ELE, 1 μmol/L ELE for 5 hours); (7) Hcy+KN-93 group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 for 5 hours); (8) Hcy+ELE group (500 μmol/L Hcy for 48 hours, then treated with 1 μmol/L ELE for 5 hours; (9) Hcy+KN-93+ELE group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 and 1 μmol/L ELE for 5 hours). Moreover, NRICs were also treated with CaMKⅡδ-siRNA lentivirus, and Nav1.5-siRNA lentivirus, negative lentivirus carrier containing green fluorescent protein (GFP) for 24 hours. The MOI values of the three groups were 10. Infection efficiency of lentivirus was determined by observing the percentage of GFP fluorescence under inverted fluorescence microscope after transfection for 24 hours, and cultured regularly with simultaneous Puro screening, then cells were grouped as Hcy+CaMKⅡδ-siRNA group, Hcy+Nav1.5-siRNA group and Hcy+negative group. The concentration of Ca2+ in NRICs ([Ca2+]i) of various groups was detected through Fluo-4/AM fluorescence probe, then 2', 7'- two chlorofluorescein diacetate (DCFH-DA) was used as a probe to detect reactive oxygen species (ROS) in NRICs by flow cytometry. The malondialdehyde (MDA) was detected by the activity of superoxide dismutase (SOD) and xanthine oxidase was detected by thiobarbituric acid colorimetry. The protein and mRNA expression level of CaMKⅡδ and Nav1.5 in NRICs were detected by Western blot and quantitative real-time PCR.@*Results@#(1) ROS, MDA and SOD were similar between NAC group and control group, ROS and MDA were significantly increased, while SOD was significantly reduced in Hcy group in a concentration-dependent manner. (2) [Ca2+]i: The level of [Ca2+]i was (155.57+7.25), (187.43+13.07), (248.98+27.22) and (307.36+15.09) nmol/L in 50, 100, 200 and 500 μmol/L Hcy groups, which was significantly higher than that in the control group ((123.18+7.24) nmol/L, P<0.01). In addition, the level of [Ca2+]i in Hcy+NAC group ((222.87+23.71)nmol/L) was significantly lower than that in Hcy 500 μmol/L group ((305.15+39.45) nmol/L, P<0.05), while [Ca2+]i level was similar between NAC group and the control group. (3) The protein expression of CaMKⅡδ and Nav1.5 was significantly upregulated in Hcy groups than in the control group. The protein expression level of CaMKⅡδ-Thr287 was significantly lower in NAC group than in Hcy 500 μmol/L group (P<0.01), however, there was no significant difference on the protein expression levels of CaMKⅡδ-Thr287 and Nav1.5 between NAC group and control group (all P>0.05). (4) The protein expression levels of CaMKⅡδ-Thr287 and the concentration of [Ca2+]i were significantly lower in Hcy+KN-93 group and Hcy+KN-93+ELE group than in Hcy 500 μmol/L group (P<0.05). [Ca2+]i concentration was significantly lower in Hcy+KN-93 group, Hcy+ELE group and KN-93+ELE+Hcy group than in Hcy 500 μmol/L group (P<0.05). (5) The mRNA and protein expression levels of CaMKⅡδ and Nav1.5 in each group infected with lentivirus: the GFP expression was ideal post lentivirus transfection for 24 hours (up to 90%), which was significantly lower in the CaMKⅡδ-siRNA group and Nav1.5-siRNA group than in the negative infection group (all P<0.05), which was similar between negative infection group and control group (P>0.05). Moreover, the mRNA and protein expression levels of CaMKⅡδ and CaMKⅡδ-Thr287 was significantly lower in Hcy+Nav1.5-siRNA group than in Hcy+negative infection group (P<0.05). The protein and mRNA levels of Nav1.5 were similar between Hcy+CaMKⅡδ-siRNA group and Hcy+negative infection group (P>0.05).@*Conclusions@#Hcy can induce calcium overload in NRICs by increasing oxidative stress, upregulating the sodium channel protein, and activating the late sodium current and phosphorylating CaMKⅡδ.
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Objective@#To discuss the prevalence and influential factors of stroke among population in Jiangxi Province.@*Methods@#Four cities in urban areas and four counties in rural areas were selected firstly, in which two districts or townships were selected; and then three communities or villages were chosen from each district and township, respectively, using the simple random sampling (SRS) method. Finally 15 269 subjects aging 15 years old or above, living in Jiangxi Province ≥6 months were randomly selected to participate in this survey from November 2013 to August 2014. Information of population characteristics, life behavior way, individual disease history were collected through questionnaire survey, and height, weight, waist circumference, blood pressure, body fat rate, visceral fat index and so on were measured by instruments. Risk factors of stroke prevalence were analyzed by the unconditioned logistic regression analysis.@*Results@#A total of 15 269 participants (6 267 males) from 15 364 eligible participants were included in the statistical analysis. Out of which, 7 793 participants came from urban areas, and their average age was (53.04±17.91) years old. In this study, 226 stroke patients (117 males) were found among15 269 participants, including 122 urban participants and 104 rural participants, whose average age was (67.76±9.74) years old. The prevalence of stroke was 1 480.12/100 000 in 2014, which was separately 1 866.92/100 000 and 1 210.84/100 000 among males and females. The prevalence of people aging (45-49) years old was 413.79/100 000 (6/1 450) , while which among people aging 75 years old and above was 3 311.62/100 000 (61/1 842) . The prevalence of stroke among residents in Jiangxi presented an uprising tendency with age increasing (linear-by-linear association χ2=62.23, P<0.01). The research showed that when other influencing factors including gender, BMI, waist circumference, pulse-pressure difference, VAI, and sleeping time in non-working days were controlled, hypertensive patients had a higher risk of stroke than people without hypertension (OR=6.88, 95%CI: 4.90-9.67), drinkers had a higher risk of stroke than non-drinkers (OR=1.56, 95%CI: 1.17-2.08), compared with people <65 years old, people aged 65-74 years old and ≥75 years old had a higher risk of stroke, the value of OR (95%CI) were 1.88 (1.36-2.59) and 1.97 (1.39-2.80), respectively, compared with people with normal body fat percentage, people whose body fat percentage on high side and people who with high body fat percentage had a higher risk of stroke, the value of OR (95%CI) were 1.71 (1.18-2.48) and 1.74 (1.18-2.56), respectively, people with sleep time >8 h had a higher risk of stroke than those with sleep time of 6-8 h.@*Conclusion@#There was a high stroke prevalence among residents in Jiangxi province. Hypertension, drinking, age, BFP and sleep duration were associated with stroke prevalence. Corresponding measures for high-risk population and risk factors should be strengthened to prevent and control the stroke.
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Objective: To explore the correlation of monocyte to HDL-C ratio (MHR) and post-operative slow lfow or no relfow in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). Methods: A total of 216 STEMI patients treated in our hospital from 2014-10 to 2016-05 were enrolled. The patients were divided into 2 groups: Slow lfow or no relfow group, the patients with TIMI grade≤2,n=43 and Normal lfow group, n=173. Receiver operating characteristic (ROC) curve was performed to assess the best cut-off value for MHR predicting slow lfow or no relfow with its sensitivity and speciifcity; Logistic regression analysis was conducted to studied weather MHR could be used as an independent risk factor for coronary slow lfow or no relfow in STEMI patients after PCI. Results: Compared with Normal lfow group, Slow lfow or no relfow group had the higher MHR (18.6±9.8) vs (10.9±5.5), P<0.001. Univariate Regression analysis indicated that MHR was a risk factor of slow lfow or no relfow occurrence (OR=2.22, 95% CI 1.58-3.28); multivariate regression analysis presented that MHR was an independent risk factor of slow lfow or no relfow occurrence (OR=1.55, 95% CI 1.01-2.38). ROC curve showed that the best cut-off value for MHR predicting slow lfow or no relfow occurrence was 13.37 with the sensitivity and speciifcity at 67.4% and 70.5% respectively, the area under curve (AUC) was 0.734, 95% CI 0.646-0.822. Conclusion: MHR was an independent risk factor for slow lfow or no relfow occurrence in STEMI patients after PCI.
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Atrial structural remodeling and electrical remodeling are the core of atrial fibrillation.Oxidative stress directly activates calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), and induces electrical remodeling and atrial structural remodeling characterized by reduced atrial effective refractory period, which becomes the pathological basis of atrial fibrillation.Therefore, the study of the relationship between the oxidative CaMKⅡ and atrial remodeling will help to elucidate the pathogenesis of atrial fibrillation and to prevent or reverse atrial remodeling by lowering CaMKⅡ phosphorylation to reduce the incidence of atrial fibrillation.
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Atherosclerosis is the main cause of coronary heart disease, Now it is thought that atherosclerosis is a chronic inflammatory disease.The ratio of Monocytes to high-density lipoprotein (MHR) is a new inflammatory marker of coronary atherosclerosis, which is measured simply and cheaply.MHR is associated with short-term and long-term incidence of cardiovascular events and morbidity of Coronary heart disease, which can be used as predictor of coronary heart disease prognosis.
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Objective@#To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT).@*Methods@#Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy.@*Results@#Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up.@*Conclusion@#This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.
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Objective To investigate the clinical value of contrast-enhanced ultrasound (CEUS) in the diagnosis and grading of acute rejection of the transplanted pancreas after simultaneous pancreas-kidney transplantation.Methods Seventy cases pancreas grafts underwent gray scale ultrasound,color Doppler flow imaging(CDFI) and CEUS examination,the contrast agent perfusion processes were observed,and the parameters of time intensity curves(time-intensity curve,TIC) were calculated.The CEUS results were compared with the pathological findings.Results Twenty-one cases were acute rejection in 70 cases,of which 10 cases were mild,8 cases were moderate and 3 cases were severe;and 49 cases were non-rejection.①Gray scale and CDFI ultrasound:The pancreatic grafts of acute rejection were edema and enlarged,the parenchyma echo were decreased.The artery resistance index(RI) were significant different between acute rejection group and non-rejection group (0.77 ± 0.05 vs 0.74 ± 0.10,P ＜0.05),but there were no significant differences between mild,moderate and severe group (P ＞0.05).②CEUS:TIC curves showed a significantly longer time to reach peak [TTP,(21.7 ± 4.3)s vs (13.0 ± 2.9) s,P ＜0.01] and significantly reduced peakintensity(PI,18.8 ± 7.9 vs 29.6 ± 2.4,P ＜0.05).There was no significant difference between the mild and moderate groups (P ＞0.05) but statistically difference was found when the severe group compared with the other two groups (P ＜0.05).Conclusions CEUS can be used to observe the perfusion of the vascular and parenchyma of the pancreas,the results also can be quantitative analyzed.It is an effective method for the diagnosis of pancreas acute rejection of simultaneous pancreas-kidney transplantation.
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Glycogen synthase kinase-3βis a multifunctional Ser/Thr kinase , and its activity has been associated with many cell processes .The mitochondrial permeability transition pore is primed by ischemia to open upon reperfusion , leading to reperfusion induced cell necrosis .Phosphorylated GSK-3βpresumably inhibits mPTP opening by multiple mechanisms , including preservation of hexokinaseⅡin mPTP complex , prevention of interaction of cyclophilin-D with adenine nucleotide translocase , inhibition of P53 activation and attenuation of ATP hydrolysis during ischemia .
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Objective To investigate effects of xeroderma pigmentosum B(XPB) gene on IL-6 induced proliferation and apoptosis in human vascular smooth muscle cells (VSMC).Methods Recombinant plasmid pcDNA3.1-XPB and vacant vector plasmid pcDNA3.1 were transfected stably into VSMC by liposome,and these cells were incubated with IL-6 at a 100 U/ml for 48 hours.The experiments were divided into six groups:blank control group; pcDNA3.1 group; pcDNA3.1-XPB group;IL-6 group; IL-6 + pcDNA3.1 group; IL-6 + pcDNA3.1-XPB group.The expression levels of XPB,Bcl-2,Bax and wild type p53 (wt-p53) were detected through reverse transcription polymerase chain reaction (RT-PCR) and Western blotting.The cell survival,cell cycle and apoptosis were examined with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry,respectively.Results The transfection of pcDNA3.1-XPB increased the expression of XPB,Bax and wt-p53 (P＜0.05 or P＜0.01),decreased the expression of Bcl-2 (P＜0.05 or P＜0.01),and reduced the IL-6 induced effects on decreasing the expression of Bax and wt-p53 and increasing the expression of Bcl-2(P＜0.05 or P＜0.01).The over expression of XPB inhibited the cell growth(q=2.95,P＜ 0.05),and reduced the positive effects of IL-6 on VSMC growth ( 102.6 +6.2) ％ vs.(124.5 + 7.9) ％,q=3.49,P＜0.05.The over expression of XPB increased the apoptosis rate of VSMC(P＜0.01 ) and the cell amounts of G0/G1 phase (q=2.99,P＜ 0.05),decreased the cell amounts of S phase(q=3.05,P＜0.05),and reduced the IL-6 induced effects on decreasing the apoptosis rate of VSMC(5.9±2.1)％ vs.(0.3±0.1)％,q=7.53,P＜0.01; the cell amounts of G0/G1 phase(70.9±6.7) ％ vs.(54.8±2.9) ％,q=6.91,P＜0.01 ;and on increasing the cell amounts of Sphase(20.2+3.6)％ vs.(36.4+7.2)％,q=8.54,P＜0.01.Conclusions XPB gene could inhibit VSMC proliferation,promote VSMC apoptosis,and reduce the effects that IL-6 promotes VSMC proliferation and inhibits VSMC apoptosis.Therefore,XPB gene is likely to be potential molecular target for treatment of atherosclerosis.
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AIM: To observe the change of subunit of NADPH oxidation enzyme complex nox - 1 protein in cardiocyte hypoxia - reoxygenation injury and the role of cardiotrophin -1.METHODS: Cardiomyocytes from the hearts of 1 -3 d old neonatal rats were prepared by a modified method. Five groups were included in the study: control; hypoxia/ reoxygenation; hypoxia/reoxygenation + CT - 1; CT - 1 + hypoxia/reoxygenation + LY294002 (PIK3/Akt inhibitor) ; CT -1 + hypoxia/reoxygenation + PD98059 (ERK inhibitor) ; CT - 1 + hypoxia/reoxygenation + DMSO. The concentration of CT -1 was 10 μg/L. The survival rate of myocytes was evaluated by MTS method. Apoptosis, mitochondrial permeability transition pore ( △ψm) and reactive oxygen species ( ROS) were detected by flow cytometry. Nox - 1 protein was determined by Western blotting. RESULTS: Apoptosis of cardiomyocytes and the level of ROS (19.7% ±1.4% vs 2.1% ± 0.5% , 14.07% ± 1.25% vs 3.54% ± 0.86% , P < 0.05 ) increased markedly after hypoxia/reoxygenation, but cardio-myocyte survival rate and the level of△ψm (40.55% ±4.25% vs 86.28% ±7.15% , P <0.01) decreased significantly. The expression of nox - 1 protein was upregulated markedly. With CT - 1 intervention, cardiomyocyte survival rate increased markedly, apoptosis, both ROS and expression of nox - 1 protein reduced significantly. The level of△ψm increased obviously. The effect of CT - 1 was inhibited by LY294002.No significant effect was observed on cells survival in DMSO group, which confirmed that LY294002 was specifically involved in blocking the protective effect of CT - 1.CONCLUSION : The expression of subunit of NADPH oxidation enzyme complex nox - 1 protein is upregulated markedly in cardiocyte hypoxia - reoxygenation injury.CT - 1 protects cardiac cells against hypoxia - reoxygenation injury by downregulating the expression of nox -1 protein to decrease the level of ROS.
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Objective To study the effect of Cardiotrophin-1 (CT-1) on cardiocyte hypoxia-reoxygenation injury,and to investigate the signaling pathways involved in the protective effect. Method This study was carried out in Key Lab of Molecular Medicine in Jiangxi Province. Cardiomyocytes from the hearts of 2-day-old Sprague-Dawley neonatal rats were prepared by a modified method. Five groups were included in the study. Group (ⅰ): control, Group (ⅱ): hypoxia/reoxygeuation, Group (ⅲ): hypoxia / reoxygenation + CT-1, Group (iv) : CT- 1 + hypoxia/ reoxygenation + LY294002 (PIK3/Akt inhibitor), Group (ⅴ): CT-1 + hypoxia / reoxygenation +DMSO. The concentration of CT-1 was 10 ng/mL. Myocytes survival rote was evaluated by MTS method, apopto-sis, mitochondrial permeability transition pore (△ψm) and reactive oxygen species(ROS) were detected by flow cy-tometer, phosphorylased GSK-3β and PI3K protein by western blotting. Analysis of variance and q test as statistical methods was used to analyze the data. Results Cardiomyocyte apoptosis and ROS increased markedly after hy-poxia/reoxygenation,but cardiomyocyte survival rate and the level of △ψm [(40.55±4.25) vs. (86.28±7.15), P < 0.01]decreased significantly. With CT-1 intervention, cardiomyocyte survival rate increased markedly (87%),apoptosis and ROS reduced significantly. The level of △ψm increased, the level of phosphorylased GSK-3β and phosphorylased PI3K protein obviously increased. The effect of CT-1 was inhibited by LY294002, but no significant effect was observed on ceils survival in DMSO group, which confirmed that LY294002 specifically in-volved blocking the protective effect of CT-1. Conclusions CT-1 can protect cardiac cells against hypoxia- reoxy-genation injury, these effects are dependent upon its ability to activate the PI3K/GSK-3β pathway.
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BACKGROUND: Our previous study showed that the activation of local renin-angiotensin system in heart and vessels contributed to hypertension and cardiovascular remodeling. However, whether oxygen free radical plays an important role in this process is still unclear. OBJECTIVE: To investigate the interventional effects of Ebselen, a kind of anti-oxidative drug, on rats administered by Nw-Nitro-L-arginine methyl easter (L-NAME) (L-NAME), inhibitor of nitric oxide synthase (NOS) for a long term, and probe into the role of oxygen free radicals (OFR) in hyper- tension and cardiovascular remodeling of NO-deficient rats. DESIGN: A randomized grouping and controlled animal trial. SETTING: Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Institute of Cardiology, Nanchang University. MATERIALS: The experiment was completed from January 2002 to March 2003 at the Animal Experimental Lab, Institute of Cardiology, Nanchang University and the Key Molecular Medical Lab of Jiangxi Province. Twenty-four Wistar rats were divided to three groups according to the random number table method: normal control group (n=8), L-NAME group (n=8), L-NAME + Ebselen group (n=8). METHODS: ①Normal control group: The rats could eat and drink routinely, and they were administrated by skim milk ball (net weigh = 4 g) before feed every night. ② L-NAME group: The rats received L-NAME in the dose of 50 mg/kg mixed in one skim milk ball everyday before feed every night. ③ L-NAME + Ebselen group: The rats were admin istered by one skim milk ball (net weigh = 2 g) mixed with L-NAME (50 mg/kg) and one skim milk ball (net weigh = 2 g) mixed with ebselen (30 mg/kg). The systolic blood pressure (SBP) was detected before LNAME was given and at the ends of the 1st, 2nd, 4th,6th and 8th weeks respectively. The rats were killed under anesthesia at the end of the 8th week, the plasma and homogenate of myocardium of apex were taken to detect the biochemical indexes, the other heart tissues were used for the histological detections. MAIN OUTCOME MEASURE: ① Dynamic changes of blood pressure were observed. The levels of NO and malondialdehyde (MDA), activities of angiotensin-converting enzyme (ACE) and superoxide dismutase (SOD) in plasma and myocardium of apex were measured. The production of superoxide anion and the levels of angiotensin Ⅱ type 1 receptor (AT1R) protein expression in myocardium of apex were determined. ③ The pathomor- phological indexes were determined. RESULTS: All the 24 rats were involved in the analysis of results without deletion. ① SBP: At the ends of the 1st, 2nd, 4th 6th and 8th weeks, SBP elevated gradually in the L-NAME group, which were significantly higher than those in the control group at the same time (P ＜ 0.05-0.01). At the end of the 8th week, the SBP was significantly lower in the L- NAME + Ebselen group than in the L-NAME group (P ＜ 0.05). ② Bio chemical indexes in plasma and homogenate of myocardium of apex: The NO level and SOD activity in myocardial tissue were significantly lower in the L-NAME group than in the normal control group (P ＜ 0.05-0.01), but significantly higher in the L-NAME + Ebselen group than in the L- NAME group (P ＜ 0.05-0.01). The production of superoxide anion, ACE activity and level of AT1R expression were all significantly higher in the L-NAME group than in the normal control group (P ＜ 0.05), but signifi- cantly lower in the L-NAME + Ebselen group than in the L-NAME group. ③ Pathomorphological indexes: The ratio of cardiac mass to body mass, thickness of left ventricle and ratio of thickness to lumen diameter of small artery were all significantly higher in the L-NAME group and L- NAME + Ebselen group than in the normal control group (P ＜ 0.05-0.01), and the thickness of left ventricle and ratio of thickness to lumen diameter of small artery were significantly lower in the L-NAME + Ebselen group than in the L-NAME group (P ＜ 0.05) CONCLUSION: Ebselen, an anti-oxidative drug, enable to attenuate the development of hypertension and cardiovascular remodeling in NO-deficient rats. By activating renin-angiotensin system (RAS), OFR may accelerate the formation of hypertension and cardiovascular remodeling, and the increased production of OFR may contribute to the development of cardiovascular remodeling. It is indicated that RAS may play an important role in the development of hypertension and cardiovascular remodeling induced by NO-deficiency
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Objective To examine whether the two vascular paracrine/autocrine factors, angiotensin Ⅱ (Ang Ⅱ) and endothelin, participate in the pathogenesis of arterial calcification. Methods Nicotine and vitamin D3 treated rats were studied. Vascular calcification was confirmed by using Von Kossa staining, measurement of calcium content,45Ca2+ uptake assay and alkaline phosphatase (ALP) activity. The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay. Angiotensinogen and endothelin mRNA levels were determined by RTPCR. Results The arterial calcium content, 45Ca2+ uptake and ALP activity were increased in calcification groups compared with control ( P ＜ 0.01 ). Administration of the angiotensin receptor antagonist losartan, the endothelin receptor antagonist bosentan, and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content, 45Ca2+ uptake and ALP activity. In addition, the plasma and aortic Ang Ⅱ and endothelin contents, and vascular angiotensinogen and endothelin mRNA expression were significantly up-regulated ( P ＜0.05).Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification, and that activation of these systems could potentiate pathogenesis of arterial calcification. ( J Geriatr Cardiol 2004;1(2) :108-113. )
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Objective: To study the effects of adrenomedullin (ADM) and proadrenomedullin N terminal 20 peptide (PAMP) alone or in combinations on the isolated rat hearts as well as the possible signaling pathways involved in their actions. Methods: In isolated rat hearts, the left ventricular pressure (LVP), LVP?dp/dtmax, coronary fluid (CF) and heart rate(HR) of the hearts infused at different concentrations of ADM and/or PAMP were determined by a 4 cannal physiological recorder, then the cAMP contents were assayed in myocardium. Results: After being infused with ADM from 10 -11 to 10 -8 mol?L -1 or PAMP from 10 -11 to 10 -8 mol?L -1 , the LVP and LVP?dp/dtmax of the isolated hearts decreased gradually in a concentration dependent manner, and at the same concentration, the effects of PAMP were more potent than those of the ADM. When ADM and PAMP were co administrated with both concentrations as low as from 10 -11 to 10 -10 mol?L -1 , the cardiac parameters were decreased more than either ADM or PAMP administrated alone. However, the inhibitory effects of ADM and PAMP were attenuated when they were in combination at higher concentrations as from 10 -9 to 10 -8 mol?L -1 . When the rat hearts were infused with ADM, PAMP,and ADM plus PAMP, the CF were always higher than those of the controls and decreased when co administrated with L NAME, an inhibitor of NOS, but the decreaseddegree of LVP and LVP?dp/dtmax were attenuated by L NAME.The cAMP contents in the left cardiac ventricle were increased significantly by ADM infusions but not changed obviously by PAMP, and were of no statistical difference in rat hearts with ADM administrated alone from those combinated with ADM and PAMP. Conclusion: These results showed that ADM and PAMP infused alone or in combinations inhibited the function of rat hearts in vitro, which might be partly involved with the NOS/NO pathway.
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Objective To investigate the relationship between urolithiasis and vitamin D 3 as well as vitamin K 3. Methods 36 adult male SD rats were randomized to control group、stone forming group、vitamin D 3 group、vitamin D 3+stone forming group、vitamin K 3 group and vitamin K+stone forming group.OPN and its mRNA of kidneys were detected,and the crystal components in urine were determined. Results Vitamin D 3 and vitamin K 3 could enhance the expression of OPN mRNA in rat kidneys of stone models.Vitamin D 3 could increase the concentration of calcium in urine significantly.Vitamin K 3 could inhibit the excretion of oxalate in urine and also inhibits the deposition of oxalate crystals in kidney. Conclusions The results indicated that vitamin D 3 may promote stone formation via various mechanisms,whereas vitamin K 3 could inhibit this process.
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AIM: To observe the effects of high hydrostatic pressure on asymmetric NG, NG-dimethyl-L-arginine (ADMA) metabolism of human vascular endothelial cells (HUVECs), and the role of renin-angiotensin system (RAS). METHODS: Cultured HUVECs of 3-6th passage were exposed to atmosphere (0 mmHg, APC), 120 mmHg (MPC), 180 mmHg (HPC). There were three groups in each pressure condition, one as control, the other two were interfered with captopril (Cap, 10 ?mol/L or 100 ?mol/L) or irbesartan (Irb, 10 ?mol/L or 100 ?mol/L) respectively. Cell proliferation was quantified by determining hexosaminidase activity at 12 h. Concentration of ADMA in conditioned medium was measured by high performance liquid chromatography (HPLC) at 12 h. RESULTS: Compared with APC group, ADMA concentration increased prominently in MPC and HPC (4.69?0.37 and 4.48?0.39 vs 0.75?0.05,P
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AIM: To study the effects of acute HIV-1 infection on gene expression in U937 human promonocyte for understanding the pathogenecis of AIDS. METHODS: The expression levels of 550 host cell RNA transcripts in U937 human promonocyte at 2-3 d after HIV-1 infection were assessed using cDNA microarray analysis, and the results were confirmed by semiquantitative RT-PCR. RESULTS: Our results showed that 38 genes were differentially regulated in the infected U937 cells at 2-3 d post infection: 26 genes were down-regulated and 12 genes were up-regulated. These genes encode a host of proteins with divergent functions in a variety of cellular processes including receptor-mediated signaling transduction, subcellular signal trafficking, apoptosis, transcriptional regulation, and chemotaxis. CONCLUSION: HIV-1 infection alters gene expression in U937 human promonocytes.
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AIM: Metallothioneins (MTs) are cysteine-rich metal-binding proteins that exert cytoprotection during metal exposure and oxidative stress. The present study was designed to investigate whether MT can directly protect NTPase on nuclear envelope from damage induced by hydroxyl radical.METHODS: Isolated hepatic nuclei from rat liver were exposed to Fe 2+ /H 2O 2 with or without MT, and the NTPase activity on nuclei was assayed using ATP and GTP as substrate, respectively. RESULTS: Incubation of rat hepatic nuclei with the Fe 2+ /H 2O 2 (in ?mol?L -1 / ?mol?L -1 : 0 1/0 5, 0 5/2 5, 1/5, 5/25) resulted in a concentration-dependent decrease in nuclear NTPase activities ( P0 05 ). In addition, incubation of hepatic nuclei with only MT had no effect on nuclear NTPase activity. CONCLUSION: These data demonstrate that hydroxyl radical generated from Fe 2+ /H 2O 2 might attack nuclear NTPase. MT antagonistically reduces toxicity of Fe 2+ /H 2O 2 system to the NTPase.
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AIM: To observe the change of nitric oxide (NO) generation system in the vascular adventitia, media and intima in septic shock rats. METHODS: The septic shock model was made in rats by caecal ligation and puncture. The intima, media and adventitia of the rat aorta were separated. NO production (NO - 2) , nitric oxide synthase(NOS) activity and L-arginine (L-Arg) transport were measured, separately. Inducible NOS (iNOS) distribution was detected by immunohistochemistry. RESULTS: Both in early and late stage of septic shock, NO - 2 from the intima was decreased by 66.1% and 78.9%( P