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1.
Although the management of chronic heart failure (CHF) has made enormous progress over the past decades, CHF is still a tremendous medical and societal burden. Metabolic remodeling might play a crucial role in the pathophysiology of CHF. The characteristics and mechanisms of metabolic remodeling remained unclear, and the main hypothesis might include the changes in the availability of metabolic substrate and the decline of metabolic capability. In the early phases of the disease, metabolism shifts toward carbohydrate utilization from fatty acids (FAs) oxidation. Along with the progress of the disease, the increasing level of the hyperadrenergic state and insulin resistance cause the changes that shift back to a greater FA uptake and oxidation. In addition, a growing body of experimental and clinical evidence suggests that the improvement in the metabolic capability is likely to be more significant than the selection of the substrate.  相似文献   

2.
Congestive heart failure (CHF) has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout (necrosis and apoptosis) plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells (CSCs) within the heart divide symmetrically and/or asym-metrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells (BMCs) to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by dif-ferentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animal CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, pla-cebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.  相似文献   

3.
Cell therapy in congestive heart failure   总被引：5，自引：0，他引：5  
Congestive heart failure （CHF） has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout （necrosis and apoptosis） plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells （CSCs） within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells （BMCs） to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animat CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.  相似文献   

4.
ＩＮＴＲＯＤＵＣＴＩＯＮＴｈｅＮａ /Ｈ ｅｘｃｈａｎｇｅｒ (ＮＨＥ)ｉｓａｐＨ ｒｅｇｕｌａｔｏｒｙｐｒｏｔｅｉｎｐｒｅｓｅｎｔｉｎｔｈｅｐｌａｓｍａｍｅｍ ｂｒａｎｃｅｏｆｃａｒｄｉｏｍｙｏｃｙｔｅｓａｎｄｏｔｈｅｒｃｅｌｌｔｙｐｅｓ.ＡｌｔｈｏｕｇｈｓｅｖｅｒａｌｉｓｏｆｏｒｍｓｏｆＮＨＥｈａｖｅｂｅｅｎｄｅ ｃｒｉｂｅｄ,ｔｈｅｐｒｅｄｏｍｉｎａｎｔｉｓｏｆｏｒｍｉｎｔｈｅｈｅａｒｔｉｓｔｈｅｕｂｉｑｕｉｔｏｕｓＮＨＥ 1 ,ｗｈｉｃｈｕｎｄｅｒｃｅｎｔａｉｎｐｈｙｓｉｏｌｏｇｉｃａｌｃｏｎｄｉｔｉ…  相似文献   

5.
Objective: In addition to pH regulation, Na+/H+ exchange (NHE) has been shown to facilitate cell growth and proliferation. However, the effects of long-term inhibition of Na+/H+ exchange on cardiac structural and functional remodeling post myocardial infarction (MI) are still controversial. The present study was therefore carried out to further investigate the effects of long-term treatment with cariporide, a specific inhibitor of NHE-1, on cardiac remodeling after MI in rats; Methods: Male Wistar rats that underwent coronary ligation were randomly selected for cariporide treatment starting 6 h after induction of MI or no treatment. Treatment was continued up to 6 weeks post MI, after which, the arterial, venous and left ventricular catheters were chronically implanted. Twenty-four h later, after hemodynamic signals were recorded in conscious rats, they were sacrificed and hearts were taken out for morphological examinations; Results: Cariporide treatment decreased the heart weight and heart weight to body weight ratio (bothP<0.05), decreased left ventricular end-diastolic pressure (P<0.001), improved myocardial contractility (dP/dt max) (P<0.05) and tended to increase the survival of treated rats compared to that of untreated infarct rats; Conclusion: The results of the present study indicate that the long-term inhibition of NHE with cariporide can attenuate cardiac structural remodeling and improve left ventricular dysfunction in infarcted rats, and suggest that Na+/H+ exchange inhibition could be an effective therapeutic strategy for myocardial infarction-induced heart failure.  相似文献   

6.
Zhao  Kun  Zhang  Jing  Xu  Tianhua  Yang  Chuanxi  Weng  Liqing  Wu  Tingting  Wu  Xiaoguang  Miao  Jiaming  Guo  Xiasheng  Tu  Juan  Zhang  Dong  Zhou  Bin  Sun  Wei  Kong  Xiangqing 《Journal of Zhejiang University. Science. B》2021,22(10):818-838
Journal of Zhejiang University-SCIENCE B - Objective: Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II...  相似文献   

7.
Thecriticalheatflux (CHF)intheforcedconvec tiveboilingwithawalljethasbeenstudied.KattoandIshii[1 ] measuredtheCHFofsaturatedwater,R1 1 3 ,andtrichloroethane (ρl/ ρg =2 0 3— 1 60 3)atatmosphericpressureforadownwardfacingplanewalljet,varyingthevelocityufrom 1 .5to 1 5m/sandtheheaterlengthLfrom 1 0to 2 0mm ,andproposedEq.(1 )topredicttheirCHFdata.　　　 qcoρghfgu=0 .0 1 6 4(ρl/ ρg) 0 .867(σρlu2 L) 1 / 3 (1 )　　KattoandHaramura[2 ] ,further,haveextendedtheirvelocityrangefromu =1 .8t…  相似文献   

8.
Objective: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). Methods: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. Results: Overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialo-protein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0- and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. Conclusion: Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.  相似文献   

9.
肖波齐  陈志远 《三明学院学报》2006,23(4):381-384,398
提出了临界热流密度的一个分形模型,根据加热表面活化点的分形分布得到了临界热流密度的表达式,从该模型中发现大空间临界热流密度(CHF)是壁面过热度、接触角和流体物理特性的函数。接触角对临界热流密度有重要的影响。沸腾表面模型预测的结果与实验数据进行了比较,两者是极好的吻合。  相似文献   

10.
Objective: To investigate the directed transplantation of allograftic bone marrow-derived mesenchymal stem cells (MSCs) in myocardial infarcted (MI) model rabbits. Materials and Methods: Rabbits were divided into 3 groups, heart infarcted model with MSCs transplanted treatment (MSCs group, n=12), heart infarcted model with PBS injection (control group, n=20), sham operation with PBS injection (sham group, n=l 7). MSCs labelled by BrdUrd were injected into the MI area of the MSCs group. The same volume of PBS was injected into the MI area of the control group and sham group. The mortality, LVIDd, LVIDs and LVEF Of the two groups were compared 4 weeks later. Tropomyosin inhibitory component (Tn I) and BrdUrd immunohistochemistry identified the engrafted cells 4 weeks after transplantation. Result: The mortality of the MSCs group was 16.7% (2/12), and remarkably lower than the control group's mortality [35% (7/20) (P＜0.05)].Among the animals that survived for 4 weeks, the LVIDd and LVIDs of the MSCs group after operation were 1.17±0.21 cm and 0.74±0.13 cm, and remarkably lower than those of the model group, which were 1.64±0.14 cm and 1.19±0.12 cm (P＜0.05); the LVEF of the MSCs group after operation was 63±6%, and remarkably higher than that of the model group,which was 53±6% (P＜0.05). Among the 10 cases of animals that survived for 4 weeks in the MSCs group, in 8 cases (80%),the transplanted cells survived in the non MI, MI region and its periphery, and even farther away; part of them differentiated into cardiomyocytes; in 7 cases (70%), the transplanted cells participated in the formation of blood vessel tissue in the MI region. Conclusion: Transplanted allograftic MSCs can survive and differentiate into cardiomyocytes, form the blood vessels in the MI region. MSCs transplantation could improve the heart function after MI.  相似文献   

11.
ObjectiveCardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II (AngII). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction (MI) through mechano-transduction and its downstream pathways. In this study, we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so, to further elucidate the underlying molecular mechanisms.MethodsWe used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis. LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation, and in vitro for 20 min on each of two occasions 6 h apart. Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic, histopathological, and molecular biological methods.ResultsOur results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines, but the protective effects on cardiac hypertrophy were limited in vitro. Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation, we inhibited caveolin-1 activity with pyrazolopyrimidine 2 (pp2) in vivo and in vitro. LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent.ConclusionsThese results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway, providing new insights for the development of novel therapeutic apparatus in clinical practice.  相似文献   

12.
Mesenchymal stem cells (MSCs) are plastic-adherent cells with a characteristic surface phenotype and properties of self-renewal, differentiation, and high proliferative potential. The characteristics of MSCs and their tumortropic capability make them an ideal tool for use in cell-based therapies for cancer, including glioma. These cells can function either through a bystander effect or as a delivery system for genes and drugs. MSCs have been demonstrated to inhibit the growth of glioma and to improve survival following transplantation into the brain. We briefly review the current data regarding the use of MSCs in the treatment of glioma and discuss the potential strategies for development of a more specific and effective therapy.  相似文献   

13.
目的:探讨外源性EGFP基因转染修饰兔骨髓间充质干细胞(m esenchymal stem cells,MSCs)的可行性。方法:用增强型荧光绿色蛋白(enhanced green fluorescent protein,EGFP)作为报告基因,以脂质体法转染骨髓间充质干细胞,观察转染结果、表达情况及对靶细胞活力的影响。结果:经荧光显微镜下观察证实:成功地对骨髓间充质干细胞实现了基因转染。结论:兔骨髓间充质干细胞能够在体外适宜的条件下进行长期培养;骨髓间充质干细胞可直接作为基因靶细胞,建立稳定表达EGFP的骨髓间充质干细胞系具有可行性,为进一步做标记的MSCs细胞的移植研究奠定基础。  相似文献   

14.
Objective  The aim of this study was to test the protective effect of mesenchymal stem cells (MSCs) on cardiomyocytes in vitro and to investigate the anti-apoptotic signaling pathway. Methods  MSCs from Sprague-Dawley (SD) rats were separated and cultured. MSC medium was collected from MSCs cultured in serum-free Dulbecco’s modified eagle medium (DMEM) under hypoxia. Cultured cardiomyocytes from neonatal SD rats were exposed to hypoxia/reoxygenation (H/R) and treated with MSC medium. The apoptotic cardiomyocytes were stained with Annexin-V-fluorescein isothiocyanate (FITC), Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). The mitochondrial transmembrane potential of cardiomyocytes was assessed using a fluorescence microscope. The expression of Bcl-2, Bax, cytochrome C, apoptosis-induced factor (AIF), and caspase-3 was tested by Western blot analysis. Results  Our data demonstrated that MSC medium reduced H/R-induced cardiomyocyte apoptosis, increased the Bcl-2/Bax ratio, and reduced the release of cytochrome C and AIF from mitochondria into the cytosol. Conclusion  MSCs protected the cardiomyocytes from H/R-induced apoptosis through a mitochondrial pathway in a paracrine manner. Project supported by the National Natural Science Foundation of China (No. 30670868) and the Natural Science Foundation of Zhejiang Province, China (No. R206007)  相似文献   

15.
目的 :研究充血性心力衰竭与甲状腺激素的关系。方法 :对 4 0例充血性心力衰竭患者及 16例正常患者分别测定三碘甲状腺原氨酸 ,四碘甲状腺原氨酸 ,反三碘甲状腺原氨酸以及促甲状腺激素水平。结果 :充血性心力衰竭程度越重 ,三碘甲状腺原氨酸水平下降越明显 ,反三碘甲状腺原氨酸水平升高越明显 ,促甲状腺激素水平正常 ,四碘甲状腺原氨酸变化不明显。结论 :三碘甲状腺原氨酸 ,反三碘甲状腺原氨酸对充血性心力衰竭的早期诊断有重要意义。  相似文献   

16.
目的：探讨Tei指数原发性高血压患者心脏功能的临床应用价值。方法：原发性高血压患者176例．按Ganau分类法将原发性高血压分为4型；正常构型（A组，46例）、向心性重构（B组，53例）、向心性肥厚（C组，40例）、离心性肥厚（D组，37例）；正常对照组35例。以常规超声心动图检查测量舒张末期室间隔、左室后壁厚度及左室内径（IVS、LVPW、LVDed），二尖瓣血流频谱图舒张早期与舒张晚期血流峰值比（E／A），左室射血分数（EF）及Tei指数，进行对比分析。结果：1.一般资料的比较：各组同年龄、性别差异均无显著性意义，C、D组病程有显著性差异，C、D组收缩压最高（P〈0．05），B、C、D组脉压最高（P〈0．05）；2．各组超声心动图结构参数比较：C组、D组LA最大（P〈0．05）；B组LVDS最小（P〈0．05），D组LVDS最大（P〈0．05）；C组IVS、LVPW最厚（P〈0．05）；B组、D组IVS、LVPW轻度增厚（P〈0．05）；C组RWT明显厚于其它各组（P〈0．01）；C组、D组LVMI质量显著增加（P〈0.01），但C组、D组之间无统计学意义；3．各组超声心动图功能参数比较：高血压各组的E／A值均减低（P〈0．05），EF只有D组与对照组比较有显著性意义；高血压各组Tei指数均较对照组增加，呈递增趋势，各组间有显著性意义。结论：Tei指数可以客观、真实的评价高血压患者不同左室构型的心功能情况，对于评估疾病的治疗效果和预后具有很高的临床应用价值。  相似文献   

17.
To examine the effects of co-culture with bone marrow mesenchymal stem cells on expansion of hematopoietic stem/progenitor cells and the capacities of rapid neutrophil engraftment and hematopoietic reconstitution of the expanded cells, we expanded mononuclear cells (MNCs) and CD34+/c-kit+ cells from mouse bone marrow and transplanted the expanded cells into the irradiated mice. MNCs were isolated from mouse bone marrow and CD34+/c-kit+ cells were selected from MNCs by using MoFlo Cell Sorter. MNCs and CD34+/c-kit+ cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion. The expanded cells were then transplanted into sublethally irradiated BDF1 mice. Results showed that the co-culture with MSCs resulted in expansions of median total nucleated cells, CD34+ cells, GM-CFC and HPP-CFC respectively by 10.8-, 4.8-, 65.9- and 38.8-fold for the mononuclear cell culture, and respectively by 76.1-, 2.9-, 71.7- and 51.8-fold for the CD34+/c-kit+ cell culture. The expanded cells could rapidly engraft in the sublethally irradiated mice and reconstitute their hematopoiesis. Co-cultures with MSCs in conjunction with two-step expansion increased expansions of total nucleated cells, GM-CFC and HPP-CFC, which led us to conclude MSCs may create favorable environment for expansions of hematopoietic stem/progenitor cells. The availability of increased numbers of expanded cells by the co-culture with MSCs may result in more rapid engraftment of neutrophils following infusion to transplant recipients. Project supported by NIH-Blood, Heart & Lung (National Institute of Health, USA, IR 01 4L70593-01) and Zhejiang Provincial Science Foundation (No. 011103397), China  相似文献   

18.
Liver fibrosis is the end-stage of many chronic liver diseases and is a significant health threat. The only effective therapy is liver transplantation, which still has many problems, including the lack of donor sources, immunological rejection, and high surgery costs, among others. However, the use of cell therapy is becoming more prevalent, and mesenchymal stem cells (MSCs) seem to be a promising cell type for the treatment of liver fibrosis. MSCs have multiple differentiation abilities, allowing them to migrate directly into injured tissue and differentiate into hepatocyte-like cells. Additionally, MSCs can release various growth factors and cytokines to increase hepatocyte regeneration, regress liver fibrosis, and regulate inflammation and immune responses. In this review, we summarize the current uses of MSC therapies for liver fibrosis and suggest potential future applications.  相似文献   

19.
A modified suction caisson(MSC), which was reported by the authors of this paper previously, comprises an external short-skirted structure that is added to a regular suction caisson(RSC). It has been proved that MSCs can improve the lateral bearing capacity and limit the deflection of the caisson compared with RSCs. A series of model tests were conducted to investigate responses of MSCs subject to uplift loading in saturated sand. The effects of external skirt dimensions on the uplift bearing capacity of MSCs were considered. In addition, the influences of the sealed top lid of the skirted structure on the uplift bearing capacity and the resulting passive suction of MSCs were also studied. It was found that the uplift bearing capacities of MSCs are 1.4-1.7 times that of RSCs. Moreover, test results in serviceable conditions show that the sealed external skirted structure of perspex-made suction caissons significantly contributed to the uplift bearing capacity as a result of passive suction.  相似文献   

20.
目的 :探讨小剂量醛固酮拮抗剂螺内酯治疗老年人重度慢性充血性心力衰竭 (CHF)疗效和安全性。方法 :采用多中心、随机、单盲、安慰剂对照、平行组试验。入选老年重度CHF患者 15 2例 ,随机分为螺内酯组 (A组 )和对照组 (B组 ) ,均予标准三联抗心衰治疗 ,A组联用螺内酯 (2 0～ 4 0mg/d) ,B组联用与螺内酯外观相同的淀粉安慰剂。治疗前和治疗后 2周、4周、8周分别进行心功能 (NYHA)分级评估 ,心电图、超声心动图、血常规、生化等检查 ,并进行对照。结果 :治疗 8周后A、B两组心功能分级、无创心排量指标均显著改善 (P <0 .0 5 ) ;与B组比较 ,A组改善更显著 (P <0 .0 5 )。无肝、肾功能损害及血脂、血糖升高 ,未见高血钾症 ,毒副作用少。结论 :应用螺内酯治疗老年人重度CHF疗效肯定、可靠、安全性好、值得推广。  相似文献   

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