Endothelial progenitor cell (EPC) is a term that refers to multiple cell types that play roles in the regeneration of the endothelial lining of blood vessels. The EPCs in bone marrow will participate in the internal...Endothelial progenitor cell (EPC) is a term that refers to multiple cell types that play roles in the regeneration of the endothelial lining of blood vessels. The EPCs in bone marrow will participate in the internal circulation in a body sub- jected to the stimulation by external factors such as injury, ischemia or drug. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. Therefore, this paper reviews the sources, isolation and culture of EPCs, the factors influencing the proliferation and activity of EPCs, and the roles of EPCs in angiogenesis.展开更多
Objective To investigate the changes of neural stem cells (NSCs) in the rat hippocampus after cerebral infarction (CI) and to evaluate the neurogenesis caused by the activation of NSCs. Methods CI models of rats were ...Objective To investigate the changes of neural stem cells (NSCs) in the rat hippocampus after cerebral infarction (CI) and to evaluate the neurogenesis caused by the activation of NSCs. Methods CI models of rats were made and rats were assigned to 6 groups: sham-operated, 1 day, 3 days, 7 days, 14 days, and 28 days after CI. The dynamic expression of bromodeoxyuridine (BrdU), polysialylated neural cell adhesion molecule (PSA-NCAM), glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark the proliferated NSCs. PSA-NCAM was used to mark the plasticity of activated NSCs. GFAP and NeuN were used to mark the differentiated NSCs. Results Compared with the controls, the number of BrdU+ cells in the hippocampus increased significantly at 1 day after CI (P<0.05), reached peak at 7 days after CI (P<0.05), decreased but still elevated compared with the controls at 14 days after CI (P<0.05), and nearly unchanged at 28 days after CI. The number of BrdU+/PSA-NCAM+ cells increased significantly at 7 days after CI (P<0.05), reached peak at 14 days after CI (P<0.05), and decreased but still elevated compared with the controls at 28 days after CI (P<0.05). The number of BrdU+/PSA-NCAM+ cells was equal to 60% of the number of BrdU+ cells in all the same period. The number of BrdU+/NeuN+ cells in the hippocampus increased significantly at 14 days after CI (P<0.05) and reached peak at 28 day after CI (P<0.05). The number of BrdU+/GFAP+cells in the hippocampus nearly unchanged after CI. Conclusion CI can stimulate the proliferation of inherent NSCs, and most proliferated NSCs may differentiate into neurons and represent neural plasticity.展开更多
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...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.展开更多
Objectives To explore the intrinsic factors related to the pathogenesis of acute arterial thrombosis (AAT) and to elucidate the patho- genesis of AAT on the basis of differentially expressed genes. Methods Patients ...Objectives To explore the intrinsic factors related to the pathogenesis of acute arterial thrombosis (AAT) and to elucidate the patho- genesis of AAT on the basis of differentially expressed genes. Methods Patients with acute myocardial infarction (AMI), stable angina (SA) and healthy controls (n = 20 per group) were recruited, and the whole human genome microarray analysis was performed to detect the differentially expressed genes among these subjects. Results Patients with AMI had disease-specific gene expression pattern. Biological functional analysis showed the function of T cells was significantly reduced, the mitochondrial metabolism significantly decreased, the ion metabolism was abnormal, the cell apoptosis and inflammatory reaction increased, the phagocytosis elevated, the neutrophil-mediated immunity increased and the post-traumatic repair of cells and tissues increased in AMI patients. The biological function in SA group and healthy controis remained stable and was comparable. Conclusions The reduced function ofT cell gene models in AAT showed the dysfunction of the immune system. The pathogenesis of AAT may be related to the inflammatory reaction after arterial intima infection caused by potential pathogenic microorganisms.展开更多
Objective To investigate the short- and long-term therapeutic efficacies of intravenous transplantation of bone marrow stem cells(MSCs) in rats with experimental myocardial infarction by metaanalysis.Methods Randomize...Objective To investigate the short- and long-term therapeutic efficacies of intravenous transplantation of bone marrow stem cells(MSCs) in rats with experimental myocardial infarction by metaanalysis.Methods Randomized controlled trials were systematically searched from Pub Med,Science Citation Index(SCI),Chinese journal full-text database(CJFD) up to December 2014.While the experimental groups(MSCs groups) were injected MSCs intravenously,the control groups were injected Delubecco's minimum essential medium(DMEM) or phosphate buffered saline(PBS).Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs.Weighted mean differences(WMD) and 95% confidence intervals(CI) were calculated for outcome parameters including ejection fraction(EF) and fractional shortening(FS),which were measured by echocardiogram after intravenous injection and analyzed by Rev Man 5.2 and STATA 12.0.Results Data from 9 studies(190 rats) were included in the meta-analysis.As compared to the control groups,the cardiac function of the experimental groups were not improved at day 7(EF:WMD=0.08,95%CI-1.32 to 1.16,P>0.01; FS:WMD=-0.12,95%CI-0.90 to 0.65,P>0.01) until at day 14 after MSCs' transplantation(EF:WMD=10.79,95%CI 9.16 to 12.42,P<0.01; FS:WMD=11.34,95%CI 10.44 to 12.23,P<0.01),and it lasted 4 weeks or more after transplantation of MSCs(EF:WMD=13.94,95%CI 12.24 to 15.64,P<0.01; FS:WMD=9.64,95%CI 7.98 to 11.31,P<0.01).Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.展开更多
Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was...Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was aimed to find out whether these miRNAs participate in regulating myocardial ischemia reperfusion (I/R) injury.Methods Apoptosis in mice hearts subjected to I/R was detected by TUNEL assay in vivo,while flow cytometry analysis followed by Annexin V/PI double stain in vitro was used to detect apoptosis in cultured cardiomyocytes which were subjected to hypoxia/reoxygenation (H/R).Taqman real-time quantitative PCR was used to confirm whether miR-15a/15b/16 were involved in the regulation of cardiac I/R and H/R.Results Compared to those of the controls,I/R or H/R induced apoptosis of cardiomyocytes was significantly iucreased both in vivo (24.4% ± 9.4% vs.2.2% ± 1.9%,P < 0.01,n =5) and in vitro (14.12% ±0.92% vs.2.22% ± 0.08%).The expression of miR-15a and miR-15b,but not miR-16,was increased in the mice I/R model,and the results were consistent in the H/R model.Conclusions Our data indicate miR-15 and miR-15b are up-regulated in response to cardiac I/R injury,therefore,down-regulation of miR- 15a/b may be a promising strategy to reduce myocardial apoptosis induced by cardiac I/R injury.展开更多
The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor (NGF...The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor (NGF) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infarcted rabbit model. Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 weeks (HMI group, n=9). Other rabbits with myocardial infarction were infused NGF to the left stellate ganglion (HMI+NGF group, 400 U/day for 8 weeks, n=8). Myocytes were isolated from regions of the noninfarcted left ventricular free wall. Action potentials and ion currents were recorded with whole-cell patch clamp. The results showed that more DADs and TA events of HMI+NGF myocytes than that of HMI and Ctrl group. Iti and ICa-L of NGF+HMI myocytes were increased significantly compared with HMI and Ctrl cells, which contributed to DADs-related triggered arrhythmia. Comparing with HM1 and Ctrl myocytes, significant prolongations of APD50 and APD90 in HMI+NGF myocytes were found. The results indicated the electrophysiological change of HMI myocytes with NGF infusion. It suggested that more events of DADs and TA in HMI myocytes with NGF treatment. The underlying mechanism may be involved in the increase of Iti and ICa-L.展开更多
Objectives This study aimed at investigating the cellular mechanism of isoproterenol (ISO) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infa...Objectives This study aimed at investigating the cellular mechanism of isoproterenol (ISO) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk (healed myocardial infarction, HMI). Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and IC,_L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of I6 and calcium influxing展开更多
Recently, we reported the unique effects of cerebral protection of the Chinese herbal medicine-Braintone (a formulation containing Radix Rhodiola, Folium Ginkgo, Radix Notoginseng and Rhizoma Ligustici Chuanxiong), ...Recently, we reported the unique effects of cerebral protection of the Chinese herbal medicine-Braintone (a formulation containing Radix Rhodiola, Folium Ginkgo, Radix Notoginseng and Rhizoma Ligustici Chuanxiong), also known as Remembrance. In the present study, we tested the hypothesis that Braintone may extend cardioprotective effects on ischemic myocardium in Wistar rats. Animal model was created by ligating of left descending coronary artery. Mortality rate and infarct volume were assessed. In addition, capillary density, antioxidant enzymes, apoptosis modulators and VEGF, eNOS mRNA expression level were investigated to reveal the underlying mechanisms. Treatment with Braintone reduced mortality rate from 41.7% to 22.2% associate with notable diminished infarct volume (30.4%±9.0% vs 18.0%±3.0%). Braintone also acted as antioxidant agent for preserving the activities of catalase (13.07±0.48 U vs 9.71±0.44 U in vehicle, P〈0.01). Furthermore, Braintone dramatically boosted the expression levels of anti-apoptotic genes Bcl-2 and Bcl-xl (1.43-, 2.30-fold, P〈0.01) as compared to vehicle group and significantly down-regulated the expression level ofpro-apoptotic gene Bax (0.84-fold, P〈0.01) while slightly inhibited Caspase-9 and Caspase-3 signals. Moreover, higher mRNA expression levels of VEGF and eNOS were observed in Braintone group consisting with a remarkable raise of capillary density (46.0±13.3 vs 27.4±12.6, P〈0.01) in myocardium. The findings indicated that Braintone markedly attenuate myocardial damage induced by ischemic insults in vivo. Braintone may confer cardioprotection via scavenging free radicals, inhibiting cardiomyocytes apoptosis and promoting angiogenesis in ischemic region.展开更多
Cannabinoid receptor type 2(CB2)activation is recently reported to promote proliferation of some types of resident stem cells(e.g.,hematopoietic stem/progenitor cell or neural progenitor cell).Resident cardiac progeni...Cannabinoid receptor type 2(CB2)activation is recently reported to promote proliferation of some types of resident stem cells(e.g.,hematopoietic stem/progenitor cell or neural progenitor cell).Resident cardiac progenitor cell(CPC)activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction(MI).This study aims to explore the role and possible mechanisms of CB2receptor activation in enhancing myocardial repair.Our results revealed that CB2receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation.AM1241 also decreased serum levels of MDA,TNF-αand IL-6 after MI.In addition,AM1241 can ameliorate left ventricular ejection fraction and fractional shortening,and reduce fibrosis.Moreover,AM1241 treatment markedly increased p-Akt and HO-1 expression,and promoted Nrf-2 nuclear translocation.However,PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241.In conclusion,AM1241 could induce myocardial regeneration and improve cardiac function,which might be associated with PI3K/Akt/Nrf2 signaling pathway activation.Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.展开更多
In this study, the cardioprotective mechanism of the combination of notoginseng total saponins and safflower total flavonoids(CNS) was investigated due to its excellently efficacy against myocardial infarction(MI)...In this study, the cardioprotective mechanism of the combination of notoginseng total saponins and safflower total flavonoids(CNS) was investigated due to its excellently efficacy against myocardial infarction(MI) in rats. After the left anterior descending coronary artery(LADCA) ligation, rats were orally administered with CNS for 7 consecutive days. CNS prevented MI-induced pathophysiological changes and significantly decreased plasma levels of myocardial enzymes, including creatine kinase MB isoenzyme(CK-MB), lactate dehydrogenase(LDH) and aspartate aminotransferase(AST). Further investigation revealed that CNS attenuated the production of inflammatory factors in plasma, including tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β). Moreover, CNS treatment decreased the expression of caspase-3 at the mR NA level in infarct tissue. Our findings demonstrated that the anti-inflammatory and anti-apoptotic properties of CNS might confer its cardioprotection against MI in rats.展开更多
To study the effect of different access routes on autologous satellite cell implantation to stimulate myocardial regeneration Methods Satellite cells were procured from skeletal muscle (gluteus max) of adult mongrel...To study the effect of different access routes on autologous satellite cell implantation to stimulate myocardial regeneration Methods Satellite cells were procured from skeletal muscle (gluteus max) of adult mongrel canine, cultured, proliferated and labeled with 4’,6 diamidino 2 phenylindone (DAPI) in vitro The cells were autologously implanted into the site of acute myocardial infarction by local injection or perfusion through the ligated distal left anterior descending coronary artery Specimens were harvested 2, 4 and 8 weeks later for histological study Results The labeling efficiency of satellite cells with DAPI was close to 100% Fluorescent cells were found at the infarcted zone, papillary muscle and local injection site Some of these cells had progressively differentiated into striated muscle fibers connected to intercalated discs The infant cells appeared different from the mature myocardium under an electron microscope Satellite cells implanted by perfusion through the coronary artery were arranged in order of consistency with host myocardial fibers The satellite cells, implanted by local injection, were found growing in a disordered way Conclusion Satellite cells, implanted by coronary artery perfusion, can progressively differentiate into striated muscle fibers, arranging in order and disseminating over the infarcted zone This approach seems more favorable for the recovery of myocardial contractile function than that of local injection展开更多
It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with myocardial infarction.The natural course of healing the infarction and the presence of putati...It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with myocardial infarction.The natural course of healing the infarction and the presence of putative homing signals within the damaged myocardium appear to favor cell engraftment during the transendothelial passage in the early days after reperfusion.However,the adverse inflammatory environment,with its high oxidative stress,might be deleterious if cells are administered too early after reperfusion.Here we highlight several aspects of the timing of intracoronary stem cell therapy.Our results showed that transplantation of bone marrow mesenchymal stem cells at 2 4 weeks after myocardial infarction is more favorable for reduction of the scar area,inhibition of left ventricular remodeling,and recovery of heart function.Coronary injection of autologous bone marrow mesenchymal stem cells at 2 4 weeks after acute myocardial infarction is safe and does not increase the incidence of complications.展开更多
文摘Endothelial progenitor cell (EPC) is a term that refers to multiple cell types that play roles in the regeneration of the endothelial lining of blood vessels. The EPCs in bone marrow will participate in the internal circulation in a body sub- jected to the stimulation by external factors such as injury, ischemia or drug. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. Therefore, this paper reviews the sources, isolation and culture of EPCs, the factors influencing the proliferation and activity of EPCs, and the roles of EPCs in angiogenesis.
基金Supported by the Advanced College Research Project from the Education Department of Liaoning province (05L094)Natural Science Foundation of Liaoning province (20072171)
文摘Objective To investigate the changes of neural stem cells (NSCs) in the rat hippocampus after cerebral infarction (CI) and to evaluate the neurogenesis caused by the activation of NSCs. Methods CI models of rats were made and rats were assigned to 6 groups: sham-operated, 1 day, 3 days, 7 days, 14 days, and 28 days after CI. The dynamic expression of bromodeoxyuridine (BrdU), polysialylated neural cell adhesion molecule (PSA-NCAM), glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark the proliferated NSCs. PSA-NCAM was used to mark the plasticity of activated NSCs. GFAP and NeuN were used to mark the differentiated NSCs. Results Compared with the controls, the number of BrdU+ cells in the hippocampus increased significantly at 1 day after CI (P<0.05), reached peak at 7 days after CI (P<0.05), decreased but still elevated compared with the controls at 14 days after CI (P<0.05), and nearly unchanged at 28 days after CI. The number of BrdU+/PSA-NCAM+ cells increased significantly at 7 days after CI (P<0.05), reached peak at 14 days after CI (P<0.05), and decreased but still elevated compared with the controls at 28 days after CI (P<0.05). The number of BrdU+/PSA-NCAM+ cells was equal to 60% of the number of BrdU+ cells in all the same period. The number of BrdU+/NeuN+ cells in the hippocampus increased significantly at 14 days after CI (P<0.05) and reached peak at 28 day after CI (P<0.05). The number of BrdU+/GFAP+cells in the hippocampus nearly unchanged after CI. Conclusion CI can stimulate the proliferation of inherent NSCs, and most proliferated NSCs may differentiate into neurons and represent neural plasticity.
基金Project (No. 20060400200) supported by the Postdoctoral ScienceFoundation, China
文摘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.
文摘Objectives To explore the intrinsic factors related to the pathogenesis of acute arterial thrombosis (AAT) and to elucidate the patho- genesis of AAT on the basis of differentially expressed genes. Methods Patients with acute myocardial infarction (AMI), stable angina (SA) and healthy controls (n = 20 per group) were recruited, and the whole human genome microarray analysis was performed to detect the differentially expressed genes among these subjects. Results Patients with AMI had disease-specific gene expression pattern. Biological functional analysis showed the function of T cells was significantly reduced, the mitochondrial metabolism significantly decreased, the ion metabolism was abnormal, the cell apoptosis and inflammatory reaction increased, the phagocytosis elevated, the neutrophil-mediated immunity increased and the post-traumatic repair of cells and tissues increased in AMI patients. The biological function in SA group and healthy controis remained stable and was comparable. Conclusions The reduced function ofT cell gene models in AAT showed the dysfunction of the immune system. The pathogenesis of AAT may be related to the inflammatory reaction after arterial intima infection caused by potential pathogenic microorganisms.
基金Supported by the Youth Project of National Natural Science Foundation(81100078)the Key Project of Chinese Ministry of Education(211207)+1 种基金Guangzhou Pearl River science and technology new star project plan(2012J2200063)Project of Guangdong Science and Technology Department(S2011040001392)
文摘Objective To investigate the short- and long-term therapeutic efficacies of intravenous transplantation of bone marrow stem cells(MSCs) in rats with experimental myocardial infarction by metaanalysis.Methods Randomized controlled trials were systematically searched from Pub Med,Science Citation Index(SCI),Chinese journal full-text database(CJFD) up to December 2014.While the experimental groups(MSCs groups) were injected MSCs intravenously,the control groups were injected Delubecco's minimum essential medium(DMEM) or phosphate buffered saline(PBS).Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs.Weighted mean differences(WMD) and 95% confidence intervals(CI) were calculated for outcome parameters including ejection fraction(EF) and fractional shortening(FS),which were measured by echocardiogram after intravenous injection and analyzed by Rev Man 5.2 and STATA 12.0.Results Data from 9 studies(190 rats) were included in the meta-analysis.As compared to the control groups,the cardiac function of the experimental groups were not improved at day 7(EF:WMD=0.08,95%CI-1.32 to 1.16,P>0.01; FS:WMD=-0.12,95%CI-0.90 to 0.65,P>0.01) until at day 14 after MSCs' transplantation(EF:WMD=10.79,95%CI 9.16 to 12.42,P<0.01; FS:WMD=11.34,95%CI 10.44 to 12.23,P<0.01),and it lasted 4 weeks or more after transplantation of MSCs(EF:WMD=13.94,95%CI 12.24 to 15.64,P<0.01; FS:WMD=9.64,95%CI 7.98 to 11.31,P<0.01).Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.
文摘Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was aimed to find out whether these miRNAs participate in regulating myocardial ischemia reperfusion (I/R) injury.Methods Apoptosis in mice hearts subjected to I/R was detected by TUNEL assay in vivo,while flow cytometry analysis followed by Annexin V/PI double stain in vitro was used to detect apoptosis in cultured cardiomyocytes which were subjected to hypoxia/reoxygenation (H/R).Taqman real-time quantitative PCR was used to confirm whether miR-15a/15b/16 were involved in the regulation of cardiac I/R and H/R.Results Compared to those of the controls,I/R or H/R induced apoptosis of cardiomyocytes was significantly iucreased both in vivo (24.4% ± 9.4% vs.2.2% ± 1.9%,P < 0.01,n =5) and in vitro (14.12% ±0.92% vs.2.22% ± 0.08%).The expression of miR-15a and miR-15b,but not miR-16,was increased in the mice I/R model,and the results were consistent in the H/R model.Conclusions Our data indicate miR-15 and miR-15b are up-regulated in response to cardiac I/R injury,therefore,down-regulation of miR- 15a/b may be a promising strategy to reduce myocardial apoptosis induced by cardiac I/R injury.
基金Supported by the General Program of National Natural Science of China(30770901)
文摘The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor (NGF) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infarcted rabbit model. Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 weeks (HMI group, n=9). Other rabbits with myocardial infarction were infused NGF to the left stellate ganglion (HMI+NGF group, 400 U/day for 8 weeks, n=8). Myocytes were isolated from regions of the noninfarcted left ventricular free wall. Action potentials and ion currents were recorded with whole-cell patch clamp. The results showed that more DADs and TA events of HMI+NGF myocytes than that of HMI and Ctrl group. Iti and ICa-L of NGF+HMI myocytes were increased significantly compared with HMI and Ctrl cells, which contributed to DADs-related triggered arrhythmia. Comparing with HM1 and Ctrl myocytes, significant prolongations of APD50 and APD90 in HMI+NGF myocytes were found. The results indicated the electrophysiological change of HMI myocytes with NGF infusion. It suggested that more events of DADs and TA in HMI myocytes with NGF treatment. The underlying mechanism may be involved in the increase of Iti and ICa-L.
基金This work was supported by the National Natural Science Foundation of China (No: 30770901).
文摘Objectives This study aimed at investigating the cellular mechanism of isoproterenol (ISO) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk (healed myocardial infarction, HMI). Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and IC,_L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of I6 and calcium influxing
基金Pharmacy School of Fudan University(Grant No. kc200602)
文摘Recently, we reported the unique effects of cerebral protection of the Chinese herbal medicine-Braintone (a formulation containing Radix Rhodiola, Folium Ginkgo, Radix Notoginseng and Rhizoma Ligustici Chuanxiong), also known as Remembrance. In the present study, we tested the hypothesis that Braintone may extend cardioprotective effects on ischemic myocardium in Wistar rats. Animal model was created by ligating of left descending coronary artery. Mortality rate and infarct volume were assessed. In addition, capillary density, antioxidant enzymes, apoptosis modulators and VEGF, eNOS mRNA expression level were investigated to reveal the underlying mechanisms. Treatment with Braintone reduced mortality rate from 41.7% to 22.2% associate with notable diminished infarct volume (30.4%±9.0% vs 18.0%±3.0%). Braintone also acted as antioxidant agent for preserving the activities of catalase (13.07±0.48 U vs 9.71±0.44 U in vehicle, P〈0.01). Furthermore, Braintone dramatically boosted the expression levels of anti-apoptotic genes Bcl-2 and Bcl-xl (1.43-, 2.30-fold, P〈0.01) as compared to vehicle group and significantly down-regulated the expression level ofpro-apoptotic gene Bax (0.84-fold, P〈0.01) while slightly inhibited Caspase-9 and Caspase-3 signals. Moreover, higher mRNA expression levels of VEGF and eNOS were observed in Braintone group consisting with a remarkable raise of capillary density (46.0±13.3 vs 27.4±12.6, P〈0.01) in myocardium. The findings indicated that Braintone markedly attenuate myocardial damage induced by ischemic insults in vivo. Braintone may confer cardioprotection via scavenging free radicals, inhibiting cardiomyocytes apoptosis and promoting angiogenesis in ischemic region.
基金supported by the National Natural Science Foundation of China(81270168,81090274,81325009,81090270 and F Cao BWS12J037)Innovation Team Development Grant by Ministry of Education of China(2010CXTD01,IRT1053)the National Basic Research Program of China(2012CB518101)
文摘Cannabinoid receptor type 2(CB2)activation is recently reported to promote proliferation of some types of resident stem cells(e.g.,hematopoietic stem/progenitor cell or neural progenitor cell).Resident cardiac progenitor cell(CPC)activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction(MI).This study aims to explore the role and possible mechanisms of CB2receptor activation in enhancing myocardial repair.Our results revealed that CB2receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation.AM1241 also decreased serum levels of MDA,TNF-αand IL-6 after MI.In addition,AM1241 can ameliorate left ventricular ejection fraction and fractional shortening,and reduce fibrosis.Moreover,AM1241 treatment markedly increased p-Akt and HO-1 expression,and promoted Nrf-2 nuclear translocation.However,PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241.In conclusion,AM1241 could induce myocardial regeneration and improve cardiac function,which might be associated with PI3K/Akt/Nrf2 signaling pathway activation.Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.
基金National Natural Sciences Foundation of China(Grant No.81573684)
文摘In this study, the cardioprotective mechanism of the combination of notoginseng total saponins and safflower total flavonoids(CNS) was investigated due to its excellently efficacy against myocardial infarction(MI) in rats. After the left anterior descending coronary artery(LADCA) ligation, rats were orally administered with CNS for 7 consecutive days. CNS prevented MI-induced pathophysiological changes and significantly decreased plasma levels of myocardial enzymes, including creatine kinase MB isoenzyme(CK-MB), lactate dehydrogenase(LDH) and aspartate aminotransferase(AST). Further investigation revealed that CNS attenuated the production of inflammatory factors in plasma, including tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β). Moreover, CNS treatment decreased the expression of caspase-3 at the mR NA level in infarct tissue. Our findings demonstrated that the anti-inflammatory and anti-apoptotic properties of CNS might confer its cardioprotection against MI in rats.
基金ThisstudywassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 39770 735 )
文摘To study the effect of different access routes on autologous satellite cell implantation to stimulate myocardial regeneration Methods Satellite cells were procured from skeletal muscle (gluteus max) of adult mongrel canine, cultured, proliferated and labeled with 4’,6 diamidino 2 phenylindone (DAPI) in vitro The cells were autologously implanted into the site of acute myocardial infarction by local injection or perfusion through the ligated distal left anterior descending coronary artery Specimens were harvested 2, 4 and 8 weeks later for histological study Results The labeling efficiency of satellite cells with DAPI was close to 100% Fluorescent cells were found at the infarcted zone, papillary muscle and local injection site Some of these cells had progressively differentiated into striated muscle fibers connected to intercalated discs The infant cells appeared different from the mature myocardium under an electron microscope Satellite cells implanted by perfusion through the coronary artery were arranged in order of consistency with host myocardial fibers The satellite cells, implanted by local injection, were found growing in a disordered way Conclusion Satellite cells, implanted by coronary artery perfusion, can progressively differentiate into striated muscle fibers, arranging in order and disseminating over the infarcted zone This approach seems more favorable for the recovery of myocardial contractile function than that of local injection
文摘It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with myocardial infarction.The natural course of healing the infarction and the presence of putative homing signals within the damaged myocardium appear to favor cell engraftment during the transendothelial passage in the early days after reperfusion.However,the adverse inflammatory environment,with its high oxidative stress,might be deleterious if cells are administered too early after reperfusion.Here we highlight several aspects of the timing of intracoronary stem cell therapy.Our results showed that transplantation of bone marrow mesenchymal stem cells at 2 4 weeks after myocardial infarction is more favorable for reduction of the scar area,inhibition of left ventricular remodeling,and recovery of heart function.Coronary injection of autologous bone marrow mesenchymal stem cells at 2 4 weeks after acute myocardial infarction is safe and does not increase the incidence of complications.