BACKGROUND:Stem cell transplantation has a promising therapeutic prospect in the treatment of myocardial infarction,but the efficacy of stem cell transplantation is limited by the low homing efficiency of transplanted cells to the heart and the low retention rate and survival rate in the heart.Exercise therapy is an important integral component of cardiac rehabilitation for patients with myocardial infarction.However,the role of exercise in stem cell therapy for myocardial infarction has not yet been clarified.OBJECTIVE:To investigate the effect of exercise(including acute exercise and chronic exercise)on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction.METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group or combination group with random number table method(n=20).Myocardial infarction model of rats in model group,transplantation group,or combination group was made by coronary artery ligation.24 hours after the model was made,the combination group underwent aerobic exercise for 8 weeks(chronic exercise,30 min/d,5 days per week),and within 5 minutes after the first exercise(acute exercise).SD rat bone marrow mesenchymal stem cells labeled with green fluorescent protein were injected into the tail vein of the transplantation group and the combination group.A part of animals from each group were taken 24 hours after the first exercise.The survival rate of stem cells transplanted into rat myocardium,sex-determining region of Y,protein expression of homing factors,oxidative stress,and inflammatory response parameters were measured.After 72 hours of the last exercise,the remaining rats were taken to detect cardiac structure and function,myocardial histological changes,and the number of Ki67+cells.RESULTS AND CONCLUSION:(1)After acute exercise:Compared with sham operation group,myocardial reactive oxygen species level,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression increased(P<0.05),and superoxide dismutase activity decreased(P<0.05)in model group.Compared with model group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression reduced(P<0.05),superoxidation dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in transplantation and combination groups.Compared with the transplantation group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression decreased(P<0.05),stem cell survival rate,sex-determining region of Y mRNA expression,superoxide dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in combination group.(2)After chronic exercise:Compared with sham operation group,cardiomyocyte cross-sectional area and collagen content increased(P<0.05),left ventricular ejection fraction and left ventricular short-axis shortening rate decreased(P<0.05)in model group.Compared with model group,cardiomyocyte cross-sectional area and collagen content decreased(P<0.05),Ki67+cells increased(P<0.05)in transplantation group.Compared with transplantation group,collagen content decreased(P<0.05),cardiomyocyte cross-sectional area,left ventricular ejection fraction,left ventricular short-axis shortening rate,and Ki67+cells increased(P<0.05)in the combination group.(3)Acute exercise improves the survival rate of exogenous stem cells by promoting stem cell homing and improving myocardial microenvironment,while chronic exercise can stimulate cardiomyocyte proliferation,inhibit cardiac remodeling,and enhance cardiac function after stem cell transplantation.Therefore,exercise can help to optimize the efficacy of stem cell transplantation after myocardial infarction in rats.

BACKGROUND:Stem cell transplantation has a promising therapeutic prospect in the treatment of myocardial infarction,but the efficacy of stem cell transplantation is limited by the low homing efficiency of transplanted cells to the heart and the low retention rate and survival rate in the heart.Exercise therapy is an important integral component of cardiac rehabilitation for patients with myocardial infarction.However,the role of exercise in stem cell therapy for myocardial infarction has not yet been clarified.OBJECTIVE:To investigate the effect of exercise(including acute exercise and chronic exercise)on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction.METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group or combination group with random number table method(n=20).Myocardial infarction model of rats in model group,transplantation group,or combination group was made by coronary artery ligation.24 hours after the model was made,the combination group underwent aerobic exercise for 8 weeks(chronic exercise,30 min/d,5 days per week),and within 5 minutes after the first exercise(acute exercise).SD rat bone marrow mesenchymal stem cells labeled with green fluorescent protein were injected into the tail vein of the transplantation group and the combination group.A part of animals from each group were taken 24 hours after the first exercise.The survival rate of stem cells transplanted into rat myocardium,sex-determining region of Y,protein expression of homing factors,oxidative stress,and inflammatory response parameters were measured.After 72 hours of the last exercise,the remaining rats were taken to detect cardiac structure and function,myocardial histological changes,and the number of Ki67+cells.RESULTS AND CONCLUSION:(1)After acute exercise:Compared with sham operation group,myocardial reactive oxygen species level,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression increased(P<0.05),and superoxide dismutase activity decreased(P<0.05)in model group.Compared with model group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression reduced(P<0.05),superoxidation dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in transplantation and combination groups.Compared with the transplantation group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression decreased(P<0.05),stem cell survival rate,sex-determining region of Y mRNA expression,superoxide dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in combination group.(2)After chronic exercise:Compared with sham operation group,cardiomyocyte cross-sectional area and collagen content increased(P<0.05),left ventricular ejection fraction and left ventricular short-axis shortening rate decreased(P<0.05)in model group.Compared with model group,cardiomyocyte cross-sectional area and collagen content decreased(P<0.05),Ki67+cells increased(P<0.05)in transplantation group.Compared with transplantation group,collagen content decreased(P<0.05),cardiomyocyte cross-sectional area,left ventricular ejection fraction,left ventricular short-axis shortening rate,and Ki67+cells increased(P<0.05)in the combination group.(3)Acute exercise improves the survival rate of exogenous stem cells by promoting stem cell homing and improving myocardial microenvironment,while chronic exercise can stimulate cardiomyocyte proliferation,inhibit cardiac remodeling,and enhance cardiac function after stem cell transplantation.Therefore,exercise can help to optimize the efficacy of stem cell transplantation after myocardial infarction in rats.

BACKGROUND:Clinical studies have shown that aerobic exercise is an important supplement to the clinical treatment of patients with pulmonary hypertension,which can alleviate the disease condition,increase exercise tolerance and improve the quality of life.However,it is not clear whether patients at different stages of pulmonary hypertension can benefit equally from exercise training. OBJECTIVE:To compare the intervention effects of early or late aerobic training on right heart failure in rats with pulmonary hypertension and explore its possible mechanism. METHODS:Sixty male Wistar rats were randomly divided into control group,model sedentary group,model early exercise group and model late exercise group,with 15 rats in each group.The model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline(60 mg/kg)in the latter three groups.The model early exercise group was given 8 weeks of treadmill aerobic exercise(60%maximum running speed,60 minutes per day,5 days a week)after modeling,while the model late exercise group was trained for 6 weeks after 2 weeks of modeling.The control and model sedentary groups were fed quietly in the rat cage for 8 weeks.After training,the exercise performance,right ventricular hemodynamics,cardiopulmonary function,cardiopulmonary histopathology,reactive oxygen species level in mitochondria,activity of mitochondrial respiratory chain complex and expressions of myocardial tissue proteins were detected. RESULTS AND CONCLUSION:Compared with the model sedentary group,exercise performance and right ventricular function improved(P<0.05),myocardial collagen content,endothelin-1,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio decreased(P<0.05),vascular endothelial growth factor and sarcoplasmic reticulum calcium-adenosine triphosphate enzyme expression increased(P<0.05),immunofluorescence intensity of mitochondrial reactive oxygen species and the protein expression of 3-nitrotyrosine decreased(P<0.05),the activities of complex I,II,IV and V increased in the model early exercise and model late exercise groups(P<0.05),but there were no significant changes in right ventricular maximum pressure,pulmonary acceleration time and pulmonary artery wall area/total vascular area ratio(P>0.05).Compared with the model late exercise group,the model early exercise group further improved exercise performance and right ventricular function,and downregulated collagen content,brain natriuretic peptide protein expression,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio(P<0.05).To conclude,although pulmonary vascular remodeling and right ventricular overload persist in rats with pulmonary hypertension,exercise training at different stages of the disease has a cardioprotective effect.The mechanism is related to the improvement of cardiac remodeling,neurohormone system imbalance,inflammatory response and mitochondrial oxidative stress.Greater benefit is gained from initiating exercise in the early stage of the disease.

BACKGROUND:Aging is associated with increased susceptibility to cardiovascular disease,and mitochondrial dysfunction plays a key role in the pathogenesis of cardiovascular disease.Regular physical activity is beneficial to cardiovascular health and can prevent and treat chronic heart disease.However,the specific mechanism of mitochondria in the protective effect of exercise on the aging heart has not yet been clarified. OBJECTIVE:To explore the effect of aerobic exercise on cardiac pathological remodeling in aging rats and to investigate the possible mechanism of mitochondrial quality control system. METHODS:Sixty Wistar rats were randomly divided into young sedentary group(6 months old),old sedentary group(20 months old)and old exercise group(20 months old)with 20 rats in each group.Rats in the young sedentary and old sedentary groups were fed in cages for 12 weeks,while those in the old exercise group underwent moderate-intensity aerobic treadmill exercise(60%of the maximal running speed,slope 0°,60 minute per day,5 days per week)for 12 weeks.After the experiment,the heart was extracted for relevant indicator tests. RESULTS AND CONCLUSION:Cardiac morphology and myocardial histopathology:compared with the young sedentary group,the rats in the old sedentary group presented with concentric cardiac hypertrophy,myocardial fibrosis,myocardial cell apoptosis and loss,and cardiac diastolic dysfunction(P＜0.05);compared with the old sedentary group,animals in the old exercise group showed reduced myocardial fibrosis and apoptosis rates,increased cell numbers,improved cardiac function(P＜0.05),and a transition in cardiac phenotype from pathological to physiological hypertrophy.Mitochondrial function:compared with the young sedentary group,the generation rate of mitochondrial hydrogen peroxide increased(P＜0.05),respiration rate and respiratory control ratio of state 3 and state 4 decreased(P＜0.05),activities of respiratory chain complexes Ⅰ,Ⅱ and Ⅳ decreased(P＜0.05),mitochondrial calcium retention capacity decreased(P＜0.05),and mitochondrial permeability transition pore opening increased(P＜0.05)in the old sedentary group.Compared with the old sedentary group,all of the above indicators were significantly improved in the old exercise group(P＜0.05).Mitochondrial quality control:compared with the young sedentary group,mitochondrial biogenesis decreased(P＜0.05),mitophagy activity increased(P＜0.05),mitochondrial fusion reduced(P＜0.05),and fission raised(P＜0.05)in the old sedentary group;compared with the old sedentary group,mitochondrial biogenesis and mitophagy activity increased(P＜0.05),mitochondrial fusion raised(P＜0.05)and fission decreased(P＜0.05)in the old exercise group.To conclude,regular aerobic exercises exert cardioprotective effects in aging rats by regulating the mitochondrial quality control system,thus reversing pathological cardiac remodeling and improving cardiac function.

Objective This study was designed to assess whether Bushen Tongluo Fang(BSTLF),a Chinese materia medica formula,can ameliorate the hypercoagulable state in rats with membranous glomerulonephritis(MGN)induced by cationized bovine serum albumin(C-BSA)in order to gain an insight into the mechanisms responsible for its therapeutic effect.Methods Seventy-two male Sprague-Dawley rats were randomly separated into six groups:the normal control group,the MGN model group,the prednisone-plus-aspirin treatment group,and the low-,moderate-,and high-dose groups of BSTLF.The model of MGN was induced by sc(preimmunization)and iv injections of C-BSA in the latter five groups.After the development of MGN model,the decoctions of BSTLF and the prednisone-plus-aspirin solution were ig administered to the treatment groups respectively twice daily for four weeks.The rats in the model group received their drinking water as vehicle controls.Urinary albumin excretion for 24 h was measured using a rat albumin ELISA kit.The platelet aggregation was analyzed by turbidimetry.The plasma level of fibri-nogen(Fib)was determined by the von Clauss assay.Radioimmunoassay was used to examine thromboxane B2(TXB2)and 6-keto-prostaglandin F1?(6-keto-PGF1?)of the renal cortex.Results Urinary albumin excretion for 24 h,maximal platelet aggregation,plasma Fib level,and TXB2 production of renal cortex in the MGN model group were significantly higher than those in the normal control group,respectively.Compared with the MGN model group,these four measurements were decreased significantly in BSTLF-treated groups.The 6-keto-PGF1? production of renal cortex in the MGN model group was subnormal but no statistically significant differences were observed between the model group and BSTLF groups.Conclusion The results of this study suggest that the administration of BSTLF could attenuate platelet aggregability,lower plasma level of Fib and reduce thromboxane A2 production by renal cortex in the rats with MGN,so that their hypercoagulable state is corrected at least partly and glomerular microthroimbosis is prevented in several ways.These effects may contribute considerably to the mechanisms of BSTLF efficacy for chronic nephritis.