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Polyunsaturated fatty acids (PUFAs) have diverse health-promoting effects, such as potentially protecting in immune, nervous, and cardiovascular systems by targeting a variety of sites, including most ion channels. Voltage-gated potassium channels of the KV7 family and large-conductance Ca2+- and voltage-activated K+ (BKCa) channels are expressed in many tissues, therefore, their physiological importance is evident from the various disorders linked to dysfunctional KV7 channels and BKCa channels. Thus, it is extremely important to learn how potassium channels are regulated by PUFAs. The aim of this review is to provide an overview of the effects of PUFAs on KV7 channels and BKCa channels functions, as well as the mechanisms underlying these effects. In summarizing reported effects of PUFAs on KV7 and BKCa channels mediated currents, we generally conclude that PUFAs increase the current amplitude, meanwhile, differential molecular and biophysical mechanisms are associated with the current increase. In KV7 channels the currents increasement are associated with a shift in the voltage dependence of channel opening and increased maximum conductance in KV7 channels, while in BKCa channels, they are associated with destabilization the pore domain closed conformation. Furthermore, PUFA effects are influenced by auxiliary subunits of KV7 and BKCa channels, associate with channels in certain tissues. although findings are conflicting. A better understanding of how PUFAs regulate KV7 and BKCa channels may offer insight into their physiological regulation and may lead to new therapeutic strategies and approaches.
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Objective:To investigate the impact of QiliQiangXin Capsules on ventricular remodeling and cardiac contraction and relaxation function in aging rats with heart failure following myocardial infarction.Methods:From August 2022 to August 2023, a total of 30 old rats were randomly assigned to three groups: sham-operated group, model group, and treatment group, with 10 rats in each group selected through a digital lottery method.The model and treatment groups were created by ligating the anterior descending branch of the left coronary artery.The rats in the treatment group received daily administration of Astragalosa hebecarpa Drabanemerosa Strong Heart Capsule(1.0 g/kg)via gavage after 4 weeks.After the 4-week drug administration period, echocardiography was performed to measure various parameters including left ventricular end-diastolic internal diameter(LVIDd), left ventricular end-systolic internal diameter(LVIDs), left ventricular ejection fraction(LVEF), left ventricular anterior wall myocardial thickness(LVAWd), mitral valve early diastolic peak flow velocity(E peak), and early diastolic velocity of mitral annulus(e peak)detected by tissue Doppler(TDI). The E/e value was calculated based on these measurements.Additionally, serum levels of B-type brain natriuretic peptide(BNP), matrix metalloproteinase 2(MMP-2), matrix metalloproteinase 9(MMP-9), and tumor necrosis factor(TNF-α)were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE)staining was employed to observe the morphological changes in myocardial tissue.Results:Compared to rats in the model group, rats in the treatment group exhibited lower left ventricular internal dimension at end-diastole(LVIDd)(9.1±0.6 mm vs.11.4±0.8 mm, P<0.01), lower left ventricular internal dimension at end-systole(LVIDs)(5.9±0.8 mm vs.8.7±0.9 mm, P<0.01), lower E/e ratio(13.4±2.0 vs.16.3±2.8, P<0.05), higher left ventricular ejection fraction(LVEF)(68.8±7.1% vs.52.0±8.4%, P<0.01), and elevated left ventricular anterior wall thickness at end-diastole(LVAWd)(1.5±0.2 mm vs.1.2±0.3 mm, P<0.05). In addition, compared to rats in the model group, the treatment group showed a decrease in brain natriuretic peptide(BNP)(0.26±0.04 μg/L vs.0.34±0.05 μg/L, P<0.01), decreased matrix metalloproteinase-2(MMP-2)(3697.0±857.7 μg/L vs.4719.5±703.5 μg/L, P<0.01), decreased matrix metalloproteinase-9(MMP-9)(87.3±13.8 μg/L vs.116.5±9.6 μg/L, P<0.01), decreased tumor necrosis factor-alpha(TNF-α)(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01), and lower TNF-α levels(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01). Histological examination using hematoxylin and eosin(HE)staining revealed that the treatment group had less severe cardiac myocyte arrangement disorder and inflammatory reaction compared to the model group. Conclusions:Qiliqiangxin Capsules were found to effectively delay ventricular remodeling and improve myocardial contraction and relaxation function in aging rats with heart failure after acute myocardial infarction.
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Objective:To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI).Methods:The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization.Results:A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI ( OR=0.881, 95% CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group ( OR=1.401, 95% CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group ( OR=0.919, 95% CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group ( OR=1.559, 95% CI 1.130-2.150; P=0.007). Conclusion:In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.
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Objective To study the effect of non-self-similar hierarchy on fracture mechanical properties and crack propagation of the biocomposite. Methods The numerical models were established by using ABAQUS, and the stiffness and crack initiation and propagation in the biocomposite with the inclination angles between the axis of the prism and mineralized collagen fibrils θ=0°,20°,40°,60°,80° were simulated by extended finite element method. Results The inclination angle θ had limited influences on biocomposite stiffness at θ≤40°, while biocomposite stiffness decreased with θ at θ>40°. The ultimate tensile strain also increased at θ>40°. Asymmetry in the crack was also found during propagation of matrix surrounded-enhanced phases at θ>0°. The crack propagatation on one side of the long axis of the mineral crystal was relatively easier than that on the other side at θ>0°. Conclusions The non-uniform distributions of cracks were found in biological hard tissues arisen from the non-self-similar hierarchy. The non-uniform crystal arrangement in the biocomposite would result in local damage rather than catastrophic fracture. The findings of this study can provide theoretical support for material design.
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Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.
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Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.
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Objective:To investigate the therapeutic effects of noninvasive ventilation on heart failure(HF)after acute myocardial infarction(AMI)in rats.Methods:A rat model of HF after AMI was established by ligation of the left ventricular branch.Thirty male Wistar rats were randomly divided into three groups according to the random number table method: sham operation group, non-treatment group and noninvasive ventilation treatment group(n=30, each group). Echocardiography was performed on the third day after surgery, and parameters including left atrial diameter(LAD), left ventricular end diastolic diameter(LVEDD), interventricular septum thickness(IVS)and left ventricular ejection fraction(LVEF)were recorded.Serum levels of brain natriuretic peptide 45(BNP45), tumor necrosis factor α(TNF-α), matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), and heat-shock protein 70(HSP70)were measured at day 3 after operation by enzyme-linked immunosorbent assays(ELISA). Morphological changes of myocardial tissue were analyzed with hematoxylin-eosin(HE)staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL).Results:Compared with the non-treatment group, LVEDD decreased[(153.9±8.1)mm/m 2vs.(164.7±10.4)mm/m 2, P<0.05]and LVEF increased[(63.9±7.6) % vs. (54.4±9.4) %, P<0.05]in the noninvasive ventilation group .Compared with the non-treatment group, serum levels of BNP45[(0.65±0.07) % vs. (0.73±0.07) μg/L, P<0.05], TNF-α(361.5±13.1) μg/L vs. (399.1±12.6) μg/L( P<0.05), MMP-2(6 892.8±530.2) μg/L vs. (7 406.0±667.5) μg/L( P<0.05)and MMP-9(143.8±5.9) μg/L vs. (151.1±8.3) μg/L( P<0.05)decreased and levels of HSP70[(1.7±0.1)μg/L vs.(1.4±0.1)μg/L, P<0.05]increased in the noninvasive ventilation group.HE staining showed focal accumulation of neutrophils in the epicardium, loss of muscle striation, disorganized cell polarity and enlarged nuclei in the non-treatment group.Meanwhile, alleviated inflammation, scattered neutrophils between cardiomyocytes and misaligned muscle striation were observed in the noninvasive ventilation group.TUNEL results showed that the myocardial apoptotic index was lower in the noninvasive ventilation group than in the non-treatment group( P<0.05). Conclusions:Noninvasive ventilation can effectively improve heart function, reduce inflammatory response and cardiomyocyte apoptosis in rats with AMI-induced HF and may be an effective treatment for HF after AMI.
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@#Traditional surgical aortic valve replacement is associated with a high risk of serious complications, especially in elderly patients with other preoperative diseases and unable to undergo thoracotomy. Therefore, transcatheter aortic valve implantation (TAVI) is now the accepted standard treatment for patients with symptomatic severe aortic stenosis at elevated risk for conventional surgical valve replacement. Currently, guidelines propose the use of dual antiplatelet therapy for the prevention of thromboembolic events after TAVI in the patients without an indication for oral anticoagulation. While, this strategy is empiric and largely based on expert consensus extrapolated from the arena of percutaneous coronary intervention. Antithrombotic therapy is associated with a significant occurrence of both thrombotic and bleeding complications, thus, the balance between thrombotic and bleeding risk is critical. This review summarizes current guidelines and the evidence underpinning them and explores the rational for using antiplatelet and/or anticoagulant strategies after TAVI.
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Deep learning (DL) has achieved state-of-the-art performance in many digital pathology analysis tasks. Traditional methods usually require hand-crafted domain-specific features, and DL methods can learn representations without manually designed features. In terms of feature extraction, DL approaches are less labor intensive compared with conventional machine learning methods. In this paper, we comprehensively summarize recent DL-based image analysis studies in histopathology, including different tasks (e.g., classification, semantic segmentation, detection, and instance segmentation) and various applications (e.g., stain normalization, cell/gland/region structure analysis). DL methods can provide consistent and accurate outcomes. DL is a promising tool to assist pathologists in clinical diagnosis.
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Objective To investigate the effect of sarcopenia on the skeletal muscle and cardiac function in elderly patients with chronic heart failure (CHF).Methods Sixty patients with CHF and sarcopenia and 60 sex and age-matched CHF patients without sarcopenia were enrolled from September 2014 to December 2015.The skeletal mass was evaluated by fat-free mass index (FFMI) and muscle function was evaluated by gait speed (GS),hand strength (HS) and the simple physical performance battery (SPPB).The cardiac function was accessed by a 6-min walk distance (6-MWD) and left ventricular ejection fraction (LVEF).Furthermore,the serum inflammation cytokines IL-6,TNF-α,and skeletal muscle biomarker C 1q were measured.Results The CHF patients with sarcopenia had lower values for skeletal muscle mass:FFMI [(17.68±0.74) vs.(18.34±0.54)kg/m2,F=33.696,P<0.05] and lower muscle function:HS [(17.26±4.20)vs.(28.85±6.43)kg,F=136.54,P<0.05],GS [(0.65±0.11) vs.(0.90±0.10)m/s,F=-12.922,P<0.05],SPPB [(6.45±2.07) vs.(7.65± 1.76),t=-3.452,P<0.05].And the cardiac function decreased significantly in patients with sarcopenia:6-MWD [(253.76 ± 72.62) vs.(340.91 ± 55.78)m,F=54.350,P<0.05],LVEF [(39.12 ± 7.02)vs.(43.83±5.81)%,t=16.060,P<0.05].Serum IL-6/TNF-α/C1q levels were significantly elevated:IL-6[(14.12± 1.40) vs.(13.46±1.06) ng/L,F=8.513,P<0.05],TNF-α [(443.43±28.06) vs.(299.37±21.53)ng/L,t=31.556,P<0.05],C1q[(578.92±23.63) vs.(504.1 1±41.77)ng/L,F=145.78,P<0.05].Conclusion The CHF patients with sarcopenia present less skeletal muscle mass,poorer skeletal function and reduced cardiac function,and higher inflammation levels.
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Objective Mouse models of sepsis-induced myocardial injury by intraperitoneal injection of lipopolysaccharide (LPS) was established in order to provide a reliable method for the research of pathogenesis of sepsis-induced myocardial injury. Methods According to the method of random number table, a total of 150 male C57BL/6 mice were divided into five groups: NC group, sham group, and LPS 10, 12, 15 mg/kg groups, with 30 in each group. Septic myocardial injury was induced by intraperitoneal injection LPS in mice; sham group was injected with equal 0.9% saline; while there was no treatment in mice of NC group. Fifteen of the 30 mice in each group were used to observe the general status of mice before and after LPS or saline injection. Twenty-four hours after LPS or saline injection, the left ventricular function was assessed by echocardiography, serum level of cardiac troponin (cTnI) was determined by enzyme linked immunosorbent assays (ELISA), and the cardiac histomorphology and ultrastructure were observed; the other 15 mice were used to monitor the 7-day mortality after LPS or saline injection. Results The mice challenged to LPS displayed symptoms of sepsis, such as depression, ruffled fur, and diarrhea. Compared with NC group, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS) were significantly decreased at 24 hours after LPS administration in LPS 10, 12, 15 mg/kg groups [LVEF: 0.459±0.044, 0.432±0.034, 0.348±0.064 vs. 0.588±0.019, LVFS: (22.36±2.60)%, (20.78±1.91)%, (16.27±3.31)% vs. (30.55±1.30)%, all P < 0.01], and cTnI levels were significantly increased (ng/L: 270.40±43.50, 281.14±41.79, 298.39±42.05 vs. 192.59±16.90, all P <0.01). Myocardium injury was observed in three LPS groups, myocardial fibrosis, interstitial edema, erythrocyte leakage and infiltrating inflammatory cells were observed under light-microscope; ultrastructural changes disorderly arranged in cardiac muscle fibers, mitochondrial swelling and even partly missing mitochondria cristae were found under transmission electron microscope (TEM), and the higher of the dose, the more sever of the damage. There was no significant difference between sham group and NC group. The 7-day mortality in LPS 10, 12, 15 mg/kg groups were 33.3%, 53.3% and 86.7%, respectively, while no death in the NC group and sham group. Conclusion For establishing the mouse model of sepsis-induced myocardial injury, intraperitoneal injection with 12 mg/kg LPS is a preferable choice in our research.
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Objective To study the effect of rhBNP on serum chemerin and IL-37 levels in acute myocardial infarction (AMI) patients undergoing emergency PCI.Methods Eighty AMI patients who underwent emergency PCI were randomly divided into cortrol group (n =40) and rhBNP treatment group (n=40).The patients in control group were treated with conventional drugs and those in rhBNP treatment group were treated with intravenous rhBNP.Their serum chemerin and IL-37 levels were measured by ELISA.Their LVEDD and LVEF were compared.Results The serum level of chemerin was significantly lower while that of IL-37 was significantly higher in two groups at 72 h and on day 7 after PCI than before PCI (P<0.05).The serum level of chemerin was significantly lower while that of IL-37 was significantly higher in rhBNP group than in control group at 72 h and on day 7 after PCI (P<0.05).The LVEDD was significantly shorter while the LVEF was significantly higher in two groups on day 7 and month 1 after PCI than before PCI (P<0.05).The LVEDD was significantly shorter in rhBNP group than in control group on day 7 and month 1 after PCI (P<0.05).Conclusion rhBNP can effectively reduce the serum chemerin level,increase the serum IL-37 level,and improve the cardiac function in AMI patients following emergency PCI.The effect of rhBNP is better than that of conventional drugs in AMI patients after emergency PCI.
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Neuregulin-1 (NRG-1) can bind with its tyrosine kinase receptor via paracrine and autocrine, activate downstream pathways and perform a series of biological reactions, and reduce pressure load and improve heart function through inhibiting sympathetic nerve excitement.Recent study identified that NRG-1 can induce pluripotent stem cell differentiation;clinical trials proved that recombinant human NRG-1 can reduce level of N terminal pro brain natriuretic peptide, rehospitalization rate and onset times of heart failure.The present article made a review on research progress of NRG-1 in cardiovascular field.
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Objective To observe the 12-lead ECG ( electrocardiogram ) characteristics of Japanese rabbits , and provide basic ECG data for cardiovascular disease research .Methods The 12-lead ECG and X-rays of 55 male Japanese rabbits were recorded in supine position after intraperitoneal injection of 20% urethane.Results ECG:① The 12-lead ECG characteristics of male Japanese rabbits were similar to humans .The rabbit heart rate was 265.5 ±36.8 beats/min, faster than that of humans .No arrhythmia was found in all the 55 rabbits.② The supine position average ECG axis was between 19 °to 250 °, varying a lot .③P wave:The shape of P wave was blunt round or a little bit sharp .P waves were all in accordance with the sinus P wave rules , which were more obvious in lead II , aVF and all chest leads .④ The PR interval was 0.063 ±0.007 s.⑤The QRS duration was 0.040 ±0.005 s.The main waves were mostly upward in leadsⅡ,Ⅲ, and aVF .The same as humans , the R/S ratios were increased by degrees in chest leads .⑥The ST segment was short, and was located in the equipotential line .⑦ The shapes of T wave were mostly round , partly had twin peaks .T waves were more obvious in leads Ⅱ,Ⅲ, aVR, and AVF and chest leads .⑧The QT interval was 0.142 ±0.015 s, and QTc was 0.306 ±0.034 s.In the X-rays, most heart shadows were in the center and right chest .Conclusions The normal values of 12-lead ECG characteristics of Japanese rabbits are obtained in this study , which are of certain application value in experimental studies of cardiovascular diseases .
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<p><b>OBJECTIVE</b>To observe the effect of Tripterygium glycosides (TG) on the expression of hypoxia-inducible factor-1α and endothelin-1 in the kidney of diabetic rats and explore the possible mechanism underlying the protective effect of TG against diabetic nephropathy.</p><p><b>METHODS</b>Sixty 8-week-old male SD rats were randomly divided into normal control group (n=10) and streptozotocin-induced diabetes mellitus (DM) model group (n=50). The diabetic model rats were then randomly divided into DM group, low-dose (8 mg/kg) and high-dose (16 mg/kg) TG treatment groups, and Irbesartan (50 mg/kg) treatment group. After 8 weeks, the levels of blood glucose (BG), 24-h urine protein (24 h Upro), serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. The pathological changes in the renal tissues were examined by optical microscopy, and the mean glomerular area (MGA) and mean glomerular volume (MGV) were measured with pathological image analysis. Immunohistochemical and Western blotting were used to detect the expression of HIF-1α and ET-1 protein in the renal tissue, and their mRNA expressions were detected using real-time fluorescence quantitative PCR.</p><p><b>RESULTS</b>HIF-1α and ET-1 expression increased in the kidney of diabetic rats. Compared with the diabetic model rats, the rats receiving TG and Irbesartan treatment showed decreased levels of Scr, BUN, 24h Upro, MGA and MGV, improved renal histopathology, and reduced expression of HIF-1α and ET-1 mRNA and protein in the renal tissue. These changes were more obvious in high-dose TG treatment group. Correlation analysis showed that the expression of HIF-1α was positively correlated with that of ET-1, and they were both positively correlated with kidney weight index (KW/BW), 24 h Upro, MGA, and MGV.</p><p><b>CONCLUSION</b>HIF-1α and ET-1 are overexpressed in the kidney of diabetic rats. TG can improve kidney damage in diabetic rats and delay the development of diabetic nephropathy by inhibiting the HIF-1α and ET-1 expression.</p>
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Animales , Masculino , Ratas , Compuestos de Bifenilo , Farmacología , Glucemia , Nitrógeno de la Urea Sanguínea , Creatinina , Sangre , Diabetes Mellitus Experimental , Metabolismo , Endotelina-1 , Metabolismo , Glicósidos , Farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia , Metabolismo , Riñón , Metabolismo , Ratas Sprague-Dawley , Tetrazoles , Farmacología , Tripterygium , QuímicaRESUMEN
The aim of the present study was to investigate the role of calcineurin in the down-regulation of left ventricular transmural voltage-dependent K(+) currents in heart failure. Transverse aorta was banded by using microsurgical techniques to create mouse heart failure model. Sham-operated (Sham) or aorta banded (Band) mice were randomized to receive calcineurin inhibitor cyclosporine A (CsA) or vehicle. The densities and kinetic properties of voltage-dependent K(+) currents, as well as action potential (AP), of left ventricular subendocardial (Endo) and subepicardial (Epi) myocytes were determined by using whole-cell patch-clamp technique. The results showed that calcineurin activity was significant higher in Endo myocytes than that in Epi ones in all the groups. Compared with Sham group, Band mice showed significantly increased calcineurin activity both in Endo and Epi myocytes. CsA significantly reduced calcineurin activity in Band mice. CsA treatment in Band mice partially reversed the down-regulation of Ito density, completely reversed the down-regulation of IK,slow density both in Endo and Epi myocytes, and Iss density in Endo myocytes. In addition, CsA treatment in Band mice partially antagonized the prolongation of action potential duration (APD), and APD at 50% (APD50) and 90% repolarization (APD90) were significantly reduced. Because of non-parallel shortening of APD in Endo and Epi myocytes, the ratio of Endo/Epi APD90 was reduced from 4.8:1 in Band mice to 2.6:1 in CsA-treated mice, which was close to that in Sham mice. The results suggest that non-parallel activation of calcineurin in Endo and Epi myocytes contributes to the down-regulation of transmural voltage-dependent K(+) currents and the amplification of transmural dispersion of repolarization (TDR) in left ventricular failure hearts. Inhibition of calcineurin may be a potential new therapeutic strategy to prevent and cure arrhythmias and sudden death in heart failure.
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Animales , Ratones , Potenciales de Acción , Calcineurina , Fisiología , Inhibidores de la Calcineurina , Farmacología , Ciclosporina , Farmacología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Corazón , Insuficiencia Cardíaca , Técnicas de Placa-Clamp , Canales de Potasio con Entrada de Voltaje , Fisiología , Función Ventricular IzquierdaRESUMEN
Objective:To evaluate the clinical therapeutic effect and mechanism of recombinant human brain natri-uretic peptide (rhBNP,Xinhuosu)in patients with acute heart failure (AHF).Methods:A total of 90 AHF patients were randomly and equally divided into rhBNP group (received intravenous injection of rhBNP based on routine treatment for 3d)and routine treatment group.Left ventricular ejection fraction (LVEF),levels of serum high sen-sitive C reactive protein (hsCRP)and matrix metalloproteinase-9 (MMP-9)were measured and compared between two groups before and after treatment.Results:Compared with before treatment,after treatment,LVEF signifi-cantly rose,levels of hsCRP and MMP-9 significantly reduced in both groups,P <0.05 or <0.01;compared with routine treatment group after treatment,there was significant rise in LVEF [(41.4±12.8)% vs.(51.3±13.9)%], and significant reductions in levels of hsCRP [(8.63±3.57)mg/L vs.(6.67±3.97)mg/L]and MMP-9 [(17.89 ±4.75)mg/L vs.(14.64±4.89)mg/L]in rhBNP group,P <0.05 or <0.01. Conclusion:The rhBNP possesses significant therapeutic effect on acute heart failure,and its mechanism may be related with reducing hsCRP and MMP-9 levels.
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Objective:To discuss effect of nicorandil on unstable angina patients With persistent Weakly positive for troponin I (TnI).Methods:A total of 111 unstable angina patients With persistent Weakly positive for TnI Were randomly divided into control group (received routine treatment,55 cases) and intervention group (received nic-orandil 5mg,3 times/d based on routine treatment,56 cases).The relief of chest pain in one Week,the recurrent hospitalization for chest pain aggravation in 3 months and the cardiac mortality rate in one year betWeen tWo groups Were observed in tWo groups. Results:Compared With control group,the relief of angina pectoris in one Week (63.6% vs. 91.1%,χ2=11.97,P=0.0005)significantly increased,re-hospitalization for chest pain aggravation in three months (56.4% vs.19.6%,χ2=15.91,P=0.0001)significantly decreased in intervention group;but cardiac mortality rate during one year betWeen tWo groups Was no significant difference (5.5% vs. 8.9%,χ2=0.50,P=0.4792).Conclusion:Nicorandil can significantly reduce the unstable angina and re-hospitalization for chest pain aggravation in patients With persistent Weakly positive for TnI,but there Was no significant difference in reducing mortality Within one year betWeen tWo groups.
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Objective To explore the change of monocyte chemotactic factor-1 protein(MCP-1)and matrix metalloproteinase-9( MMP-9)of patients with coronary artery disease( CAD)following percutaneous coronary interventional( PCI). Methods Fifty patients underwent PCI procedures for CAD compromising a single coronary artery were selected as PCI group and 30 healthy individuals with normal findings by coronary angiography were selected as the control group. Plasma MCP-1 and MMP-9 were measured in all the subjects. Results The plasma MCP-1 level of patients with CAD after PCI was(19. 87 ± 5. 31)ng/ L,higher than that before operation((15. 71 ± 5. 23)ng/ L,t = 3. 95,P < 0. 01). Whereas in the control group,the MCP-1 level after coronary angiography was(13. 78 ± 5. 58)ng/ L,which was as same as that before operation (12. 42 ± 5. 39 ng/ L,P = 0. 34). Plasma MMP-9 level in the CAD patients after PCI procedures was(22. 69 ± 5. 97)mg/ L,higher than that before operation((19. 52 ± 5. 72)mg/ L,t = 2. 71,P < 0. 01). There was no significant difference in term of plasma MMP-9 level in control group befor and after operation((17. 53 ± 5. 51) mg/ L vs.(16. 69 ± 5. 42)mg/ L,P = 0. 55). Conclusion Plasma MCP-1 and MMP-9 increase in CAD patients following PCI procedures. But their roles in the vascular restenosis following the procedures need further investigation.
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The study is to explore the effect of total glucosides of paeony (TGP)on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats, and discuss the protection of TGP in diabetic nephropathy and possible mechanism. Ninety male SD rats of 8 weeks age were randomly divided into normal control group (n = 10) and model group (n = 80). Rats of the normal control group were fed with regular diet, while rats of the model group were fed with high-fat high-sugar diet and 4 weeks later were given an intraperitoneal injection of 35 mg x kg(-1) streptozotocin (STZ). The successfully induced type 2 diabetic rat models were then randomly divided into DM group, three TGP (50, 100, 200 mg x kg(-1) x d(-1)) treatment group and tripterygium wilfordii glycosides (8 mg x kg(-1) x d(-1)) control group. Rats of DM group and each treatment group were given high-fat high-sugar diet. At week 14, the levels of blood sugar, 24 hour urine protein, serum creatinine and blood urea nitrogen were tested. The rats were then sacrificed. Renal pathological changes were examined. Renal tissue Wnt-1 and β-catenin expressions were detected by immunohistochemical assay. Wnt-1 mRNA and β-catenin mRNA expression was semi-quantified by RT-PCR. Wnt-1 protein and β-catenin protein expression was semi-quantified by Western blot. The Result show that Wnt-1 and β-catenin expression increased in kidney of high-fat high-sugar induced type 2 diabetic rats. Compared with diabetic group, the level of serum creatinine, blood urea nitrogen, 24 h urine protein, mean glomerular area and mean glomerular volume were decreased, renal histopathology were improved, expression of Wnt-1 and β-catenin mRNA and protein was reduced in TGP group. Tripterygium wilfordii glycosides had the similar effect. In conclusion, these results showed that Wnt/β-catenin abnormal activation in kidney of type 2 diabetic rats, TGP can improve kidney damage in diabetic rats and delay the development of diabetic nephropathy by inhibit the Wnt/β-catenin signaling pathway.