The clinical effect of sacubitril valsartan combined with dapagliflozin in heart failure with reduced ejection fraction and non-diabetes patients / 西安交通大学学报(医学版)

【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.

Clinical Feature Analysis of Papillary Muscle Hypertrophic Cardomyopathy in 21 Patients / 中国循环杂志

Objective: To explore the clinical and magnetic resonance imaging (MRI) features of papillary musclehypertrophic cardiomyopathy. Methods: Our research contained 2 groups: Papillary muscle hypertrophic cardiomyopathy group,n=21 patients treated in our hospital from 2013-01 to 2015-12 including 18 male and 3 female; Control group,n=50 subjects without cardiovascular disease those were conifrmed by our hospital at the same period of time. Clinical and MRI examinations were conducted in all patients, the ifndings were compared between 2 groups. Results: Compared with control subjects, papillary musclehypertrophic cardiomyopathy patients had the main symptoms of shortness of breath, chest tightness and pain; associated with systolic murmur; ECG could be normal or with T wave inversion; cardiac MRI showed that 1/2 papillary muscle diameter>1.1cm. Blood levels of triglyceride, left atrial diameter, inter-ventricular septum thickness, the values of E/A and EDT were statistically different between 2 groups, allP<0.05. Conclusion: Clinical features of papillary muscle hypertrophic cardiomyopathy were lack of speciifcity, the morbidity and clinical signiifcance should be further investigated.

Effect of adipose-derived mesenchymal stem cell transplantation on inflammatory response and ventricular remodeling after myocardial infarction / 中国组织工程研究

BACKGROUND:Whether adipose-derived mesenchymal stem cells are able to exert immunomodulatory effects in the treatment of myocardial infarction, as wel as the best time, is less reported. OBJECTIVE:To observe the effect of adipose-derived mesenchymal stem cells on inflammatory reaction and ventricular remodeling after myocardial infarction, and to explore the possible mechanisms of adipose-derived mesenchymal stem cells for the treatment of myocardial infarction. METHODS:Enzyme digestion method was employed to isolate and culture rat adipose-derived mesenchymal stem cells. By ligation of the left anterior descending coronary artery, we established animal models of myocardial infarction in 40 rats. The rats were randomly divided into four groups:sham group, control group (injected high-glucose Dulbecco’s modified Eagle’s medium), 3-hour transplantation group (transplanted adipose-derived mesenchymal stem cells after 3 hours of myocardial infarction), 7-day transplantation group (transplanted adipose-derived mesenchymal stem cells after 7 days of myocardial infarction). After 14 days of operation, the levels of tumor necrosis factor-αand interleukin-10 in the plasma were detected by enzyme linked immunosorbent assay. After 28 days of operation, the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular ejection fraction and left ventricular fractional shortening were measured by echocardiography. RESULTS AND CONCLUSION:Compared with the control group, in the 3-hour transplantation group and 7-day transplantation group, the levels of tumor necrosis factor-αwere significantly lower (P<0.01), and the levels of interleukin-10 were significantly higher (P<0.01) at postoperative 14 days;the left ventricular end diastolic diameter and left ventricular end systolic diameter in the two transplantation groups were also significantly smal er (P<0.05), but left ventricular ejection fraction and left ventricular fractional shortening were significantly elevated (P<0.05), which was more apparent in the 3-hour transplantation group than the 7-day transplantation group. Adipose-derived mesenchymal stem cells transplantation in acute phase of myocardial infarction can suppress the inflammatory response, regulate the cytokine network equilibrium, and thus delay ventricular remodeling and improve cardiac function.

Sodium channel blockers inhibit the differentiation of rat bone marrow mesenchymal stem cells into cardiac-like cells / 中国组织工程研究

10.3969/j.issn.2095-4344.2013.23.001

Cardioprotective effects of atorvastatin plus trimetazidine in percutaneous coronary intervention

Objective: To explore the effects of preoperative administration of conventional doses of atorvastatin plus trimetazidine on the myocardial injury of patients during the perioperative period of percutaneous coronary intervention [PCI]

Methodology: 475 cases of acute coronary syndrome patients before PCI were randomly divided into the control group [238 cases] and experimental group [237 cases].The control group was treated with conventional doses of atorvastatin calcium [20 mg each time, once a night], and the experimental group was treated with conventional doses of atorvastatin calcium plus trimetazidine hydrochloride [20 mg each time, tid] for 3 d. After PCI, preoperative and postoperative 24 h concentrations of serum creatine kinase MB isoenzyme [CK-MB], cardiac troponin I [cTnI] and high sensitivity C-reactive protein [hs-CRP] as well as activity of myeloperoxidase [MPO] were investigated. Left ventricular ejection fractions of the patients were then examined 4 weeks later

Results: Postoperative 24 h cTnI concentration and elevated MPO activity of the experimental group were significantly lower than those of the control group [P < 0 05]. CK-MB activities and hs-CRP concentrations of the two groups did not differ significantly [P > 0 05]

Conclusion: The administration of conventional doses of atorvastatin plus trimetazidine three days before PCI is able to protect the perioperative patients from myocardial injury

Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure / 老年心脏病学杂志（英文版）

Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

Vena cava thrombosis after vena cava filter placement:Incidence and risk factors / 老年心脏病学杂志（英文版）

Background The objective of this study was to assess the clinical safety and efficacy of vena cava filter (VCF) placement,with particular emphasis on the incidence and risk factors of inferior vena cava thrombosis (VCT) after VCF placement.Methods Clinical data of patients with venous thromboembolism (VTE),with or without placement of VCF,were analyzed in a retrospective single-center audit of medical records from January 2005 to June 2009.The collected data included demographics,procedural details,filter type,indications,and complications.Results A total of 168 cases of VTE (82 with VCF; 86 without VCF) were examined.Over a median follow-up of 24.2months,VCT occurred in 18 of 82 patients with VCFs (11 males,7 females,mean age 55.4 years).In 86 patients without VCFs,VCT occurred in only 6 individuals (4 males,2 females) during the study period.VCT was observed more frequently in patients fitted with VCFs than in those without VCFs (22% vs.7.0%).Conclusions The incidence of VCT in patients with VTE after VCF implantation was 22% approximately.Anticoagulation therapy should be continued for all patients with VCF placement,unless there is a specific contraindication.Almost all instances of VCT in patients with VCF implants in our study occurred after stopping anticoagulation treetment.The use of VCFs is increasing,and more trials are needed to confirm their benefit and accurately assess their safety.

Role of hepatocyte growth factor in diagnosing and predicting recurrence of stroke / 药物分析学报

Objective To research whether serum hepatocyte growth factor (HGF) level increases in ischemic stroke and hemorrhagic stroke, and explore the relationship between the serum HGF level and stroke recurrence. Methods We studied a total of 92 consecutive acute stroke patients who had been admitted to hospital within 24h of onset from 6 participating hospitals in Xi'an from January 2000 to May 2004. All patients were divided into ischemic stroke group and hemorrhagic stroke group according to the results of brain computed tomography (CT) scan or MRI on admission. Patients in stroke groups were divided into recurrent group and non-recurrent group. Healthy volunteers or patients without cerebrovascular diseases comprised the control group. Stroke and control groups were strictly matched with 1∶1 ratio. The patients were followed up for 4 years. Serum HGF was tested with enzyme-linked immunosorbent assay (ELISA). Results Serum HGF of stroke patients was significantly higher than that of control group (P<0.05). The serum HGF level in recurrent group was higher than that in non-recurrent group of ischemic patients, and there was no significant difference in hemorrhagic ones. Conclusion These results indicate that serum HGF may be used as a diagnostic marker for stroke, and serum HGF level is helpful in predicting the recurrence of ischemic stroke.

Oleanolic acid-induced apoptosis and its relation with intracellular calcium in human lung adenocarcinoma A549 cells / 药物分析学报

Objective To investigate the effect of oleanolic acid (OA) on apoptosis, correlation between apoptosis and intracellular calcium, and its mechanism in human lung adenocarcinoma cell line A549. Methods Human lung adenocarcinoma A549 cells were incubated in vitro and assigned with OA concentrations of 0, 10, 20 and 40μg/mL. The apoptosis status of A549 cell line was detected with Annexin V-FITC/PI by flow cytometry (FCM); fluorescence intensity (FI) of A549 cells was assessed and the level of intracellular calcium was calculated at 24 hour of OA intervention. The relation between apoptosis and calcium FI was illustrated by curve fitting. Results FCM showed that 10, 20 and 40μg/mL of OA could induce A549 cell apoptosis, which followed a concentration-effect pattern; 24-hour intervention with 20μg/mL and 40μg/mL OA showed increased A549 cell apoptosis, and was significantly different from that with 0μg/mL OA (P<0.01). The FI of intracellular calcium concentration in 10, 20 and 40μg/mL OA groups was significantly higher than that in 0μg/mL group after 24 hours' intervention, and the FI showed a trend of increase with increased OA concentration (P<0.01). Curve fitting showed a significant correlation between apoptosis rate and intracellular calcium concentration in A549 cells (r=0.981, P<0.01). Regression equation was Y=0.508X-1.627. Conclusion OA plays a role in inducing apoptosis of human lung adenocarcinoma cells in a concentration-dependent manner. The OA-induced apoptosis is responsible for intracellular calcium overload of the tumor.

Comparative study on ghrelin level change and its related factors in hypertensive elders with psychological distress / 药物分析学报

Objective To investigate the change of plasma ghrelin level and explore the related factors of ghrelin alteration in elderly hypertensive patients with psychological distress. Methods A total of 300 elders, who were screened with Hamilton Anxiety Scale (HAMA), Hamilton Rating Scale for Depression (HAMD), and the Symptom Checklist-90 (SCL-90) for psychological stress and somato-psychological manifestations respectively, were divided into hypertension group (n=148) and non-hypertension group (n=152). Their blood samples were collected to measure the plasma level of ghrelin and total cortisol on the same day. Results The incidences of anxiety and depression were 27.7% and 11.7%, respectively, in all the enrolled elders. However, the rates of psychological distress, particularly anxiety, were significantly higher in the hypertensive elders than in the non-hypertensive ones (43.2% vs. 12.5%). Anxiety was positively related to the cortisol level but negatively related to the plasma ghrelin level, and the latter two were negatively correlated with each other. Conclusion Chronic increase of plasma cortisol induced by long-term anxiety can lead to the reduction of ghrelin level, which then adversely affects blood pressure in elders with psychological distress. Therefore, ghrelin might be a selective antihypertensive medicine for hypertensive elders with anxiety.

Red blood cell level is increased in obese but not in non-obese patients with coronary heart disease / 老年心脏病学杂志（英文版）

Objective To examine the changes of red blood cell levels in the obese and non-obese patients with coronary heart disease (CHD) and its clinical significance. Methods 230 cases of coronary heart disease were selected and divided into the obese group and the nonobese group. Obesity and non-obesity were defined based on the body mass index (BMI I (Y) 28.0kg/m2), or waist-hip ratio (men> 0.9, women> 0.85). In addition, 130 healthy subjects were recruited as controls. The pathological status of coronary lesions was quantitatively analyzed according to the Coronary Vascular Image Segmentation Evaluation Criteria (American Heart Association 1984) and the Gensini scoring system. Results of the changes of both the hemoglobin levels and the red blood cell count in the obese group, the nonobese group with CHD and the control group were compared. Besides, Multivariant Logistic Regression Analysis was applied to assess the correlation between the red blood cells and the coronary artery disease. Results The red blood cell count and the level of hemoglobin in the obese group with CHD was higher than that in the non-obese group with CHD [(4.35 ± 0.55) and (4.13 ± 0.56) 109/L; (136.71 ± 15.87) and (129.96 ± 16.23) g/L, P < 0.05 in both]; the proportion of acute coronary syndrome in the obese group with CHD was higher in the obese group with CHD than that in the non-obese group with CHD (P<0.05); Multivariant logistic regression analysis also showed that the red blood cell count was positively correlated with obesity with CHD.Conclusion The red blood cell count and the level of hemoglobin in the obese group were higher than those in the non-obese group; the increase of red blood cell count and hemoglobin level is one of the independent risk factors for the obese patients with CHD.

Correlation between expression of lung resistance-related protein and angiogenesis in non-small cell lung cancer / 西安交通大学学报(医学版)

Objective To investigate the changes in lung resistance-related protein (LRP) and vascular endothelial growth factor (VEGF) expressions and micro-vessel density (MVD) in non-small cell lung cancer (NSCLC), and to elucidate their possible relationship and mechanism. Methods Immunohistochemistry was used to detect changes in LRP and VEGF expressions, and MVD level in lung tissues of 56 NSCLC cases and 27 normal controls. Results ① LRP expression (66.1%) was concentrated in the cytoplasm of cancer cells, which was significantly higher than that in lung tissues of control group (P<0.01); the significance was not related to the pathological type. There was no significant difference in LRP expression among gender, TNM stage, lymph node metastasis, and two-year survival in NSCLC (P>0.05). ② In comparison to the control group, NSCLC group had significantly increased VEGF expression (P<0.01), which was not related to the pathological type. VEGF expression in NSCLC group had a significant association with TNM stage and lymph node metastasis (P<0.05). ③ The NSCLC group had a significantly higher MVD than the control group (P<0.01), which was not affected by the pathological type or degree. MVD value (18.5±5.8) of stage Ⅲ and Ⅳ in NSCLC group was significantly higher than that (13.8±5.1) of stage Ⅰ (P<0.05); MVD value for patients with lymph node metastasis was higher than that without lymph node metastasis (P<0.05); MVD value for patients with two-year survival was less than those who died within two years (P<0.01). ④ NSCLC group with high VEGF and LRP expressions had a consistently increased MVD value (P<0.05). Conclusion There is a certain relationship between tumor angiogenesis and LRP expression in NSCLC. VEGF is responsible for the high expression of LRP through up-regulating LRP gene and augmenting tumor MVD. Inhibition of angiogenesis in tumor is expected to reduce or inhibit drug resistance to NSCLC.

Relationship of C-reactive protein and fibrinogen changes with left atrial size in atrial fibrillation and flatter patients / 西安交通大学学报(医学版)

Objective To compare the changes in fibrinogen (Fib), C-reactive protein (CRP) and left atrial (LA) size between patients with atrial flatter (AFL) and those with atrial fibrillation (AF) to explore the relations among them. Methods We selected 53 AF patients (including 16 cases of paroxymal AF, 13 of persistent AF and 24 of permanent AF) and 18 patients with AFL; the control group consisted of 32 cases of sinus rhythm (SR). In all the patients, ECG or Horter and UCG were conducted; Fib and CRP were measured. The levels of the above indexes in AF group, AFL group and subgroups were compared with each other, and with those in the control group. Correlation analysis between CRP and LA size was made. Results Fib, CRP and LA size in AF group were significantly different from those in AFL and SR groups, but did not differ between the latter two groups. So did other parameters among the three groups. CRP in persistent AF and permanent AF differed significantly from that in AFL, SR and paraxymal AF. LA size in the groups of persistent AF differed from that in SR group, but there was no difference between those in persistent AF and AFL groups. LA size in permanent AF was significantly different from that in AF, AFL and SR. Positive significant linear correlations were found between CRP and LA size in AF (r=0.33). Conclusion Hypercoagulable state exists in AF; the AF. Positive correlation exists between LA size and inflammatory reaction; there is no hypercoagulable state in AFL.

The coagulation factor VII gene polymorphisms in patients with myocardial infarction in Ningxia Hui and Han populations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the characteristics for activated coagulation factor VII(F VIIa) and the R353Q, -323 0/10 bp, HVR4 polymorphisms in the gene in patients with coronary heart disease (CHD) and myocardial infarction from Ningxia Hui and Han populations.</p><p><b>METHODS</b>Four hundred and twenty angiographically proven CHD patients in the Hui population, and 508 healthy blood donors were tested for their plasma levels of coagulation factor VII using recombinant tissue factor method. The coagulation factor VII gene R353Q, -323 0/10 bp and HVR4 genotypes were identified by polymerase chain reaction. In addition, 600 Han patients with CHD and 604 healthy Han control subjects were also investigated.</p><p><b>RESULTS</b>(1) The plasma F VIIa levels was significantly higher in patients with CHD and myocardial infarction than that in healthy control subjects and angor pectoris (P<0.01) in both Hui and Han populations. (2) There were significant differences in the distribution of genotypes and allelic frequencies of the R353Q between myocardial infarction and angor pectoris disease in the Hui population (P<0.05). So was the -323 0/10 bp locus in both the Hui and Han population. (3) The F VIIa level was significantly higher in individuals with RR genotype than those of Q allele carriers in the Hui population.</p><p><b>CONCLUSION</b>There are polymorphisms of the F VII gene R353Q, -323 0/10 bp and HVR4 in the Hui and Han populations. The Q allele might be a protective factor against myocardial infarction in the Hui, and the plasma F VIIa level may be influenced by the R353Q polymorphism of the F VII gene. The 10 allele may be a protective factor against myocardial infarction in both the Hui and Han populations.</p>

Chronic salt-loading downregulates large-conductance Ca2+-activated potassium channel in mesenteric arterial smooth muscle cells from SD rats / 药物分析学报

Objective Large-conductance culcium-activated potassium (BKCa) channel modulates vascular smooth muscle tone. In the present study, we tested the hypothesis that salt, one of the factors which significantly influence bleed pressure (BP), can regulate BKCa activity and then elevate blood pressure. Methods Male Spragne-Dawley rats aged 6 weeks were randomized into high salt diet group (HS) and control group, fed with high salt diet (containing 5% NaCi) and standard rat chow (containing 0.4% NaCl) respectively for 16 weeks. Tail systolic blood pressure (SBP), body weight (BW) and 24-hour urinary output were tested every 4 weeks. Content of urinary Na+ was detected using flame spectrophotometrical method. At the end of 16 weeks, all the rats were killed, the mesenteric arteries were obtained, and single mesenteric smooth muscle cells were isolated at once. The resting membrane potential (Em), the total potassium currents and the currents after perfusion with TEA solution of the cells were all recorded by whole cell patch clamp. The transcriptions of BKCa channel α and β1 sobunits in mesenteric arterial vascular smooth muscle cells (VSMC) of each group were calculated by real-time RT-PCR. Results There was no difference in SBP and BW at each stage between control group and HS group; the urinary Na+ level in HS animals was elevated significantly after 4 weeks.The negative values of Em in HS group VSMCs were reduced compared with these in the control group. Transcriptions of β1 subanit of BKCa channels were decreased in HS group, but α subunit transcriptions did not differ between the two groups. Whole cell potassium currents did not differ hetween HS and control groups, but BKCa currents of HS group VSMCs were lower than these of control group ones. Conclusion Even without elevating SBP, salt-loading can still modulate the expression and activity of BKCa channel in the mesenteric arterial VSMC and elevate vascular tone.

Serum concentrations of laminin and fibronectin in patients with acute coronary syndromes / 药物分析学报

Objective To study the serum iaminin (LN) and fibronectin (FN) changes in acute coronary syndromes (ACS), and explore the role of them in assessing the severity of ACS. Methods This study included 46 ACS patients [25 with acute myocardial infarction (AMI) and 21 with unstable angina (UA)], 51 stable angina (SA) patients and 47 people without CHD as controls. Serum levels of LN, FN, fibrinogen and blood fat were assessed. Coronary angiography were performed on 49 of them. Results The serum concentration of LN was lower in ACS patients [(85.20±27. 57)ng/mL], higher in SA patients [(116. 80 ± 28. 80)ng/mL] as compared to that in the control group [(100.06±29.96)ng/mL], with significant difference among the groups (P<0.05). No difference was found in FN among the three groups. However, the subgroup analysis in the group with ACS showed that the serum concentration of FN was significantly higher in UA patients [(229.60±121.39)μg/mL ], and lower in AMI patients [(108.31±47.12) μg/mL ]. The serum LN and FN concentration could respectively enter the logistic regression equations of ACS patients and US patients. Neither LN nor FN concentration was correlated with narrowing of coronary artery of angiography. Conclusion Serum LN and FN level may be a useful indicator for stability of atherosclerosis plaque in coronary arterial disease patients, but could not predict the extent of narrowing in coronary angiography.

The clinical role of increase of serum matrix metalloproteinase-8 concentration in patients with acute coronary syndrome / 药物分析学报

Objective To study the clinical role of the variation of serum matrix metalloproteinase-8 (MMP-8)concentration in patients with acute coronary syndrome (ACS). Methods ELISA method was adopted to detect serum MMP-8 concentration and to observe concentration's differences and features among 80 selected ACS cases (43 acute myocardial infarction and 37 unstable angina pectoris), 43 stable angina pectoris (SAP) cases and 37 control cases.And meanwhile the atherosclerosis risk factors of each case, such as age, sex, hypertension, body mass index, smoking,family history, diabetes, and hyperlipidemia were collected and analyzed as a whole. Results First, serum MMP-8 concentration reached the highest point in ACS, and there was significant difference between SAP and control groups (P<0.01). Second, sermn MMP-8 in AMI was much higher than that in UAP with significant difference (P<0.01). There was no difference between UAP and SAP groups (P>0.05). Third, Logistic regression analysis revealed that serum MMP-8 concentration might be the indicator of ACS (B=4.493, P=0.000), particularly, that of AMI (B=9.961,P=0.000). Fourth, linear correlation and linear regression analysis found that only neutrophil was likely to influence serum MMP-8 concentration (r=0.274, P=0.001). Fifth, in the diagnosis of ACS, the area under ROC curve of MMP-8 was 0.785, the sensitivity and specificity were 68.6% and 76.5%, respectively. Conclusion ① Serum MMP-8 concentration has close relationship with the occurrence of ACS, particularly with AMI;② Serum MMP-8 concentration may be one of the predicting indicators of ACS and particularly of AMI;③ Neutrophil may be correlated with serum MMP-8 concentration;④ MMP-8 is of somewhat valuable in diagnosing ACS.

Differentiation of rat mesenchymal stem cells into smooth muscle cells induced by cell-to-cell contact / 中国组织工程研究

BACKGROUND: It is conceivable that bone marrow stem cells can differentiate into smooth muscle cells (SMCs) and contribute to neointimal formation in atherogenesis. However, the mechanism remains unknown. The "milieu-induced-differentiation" hypothesis focuses on the key role of cell-to-cell contact and cytokine on the differentiation of stem cells. Bone marrow mesenchymal stem cells (MSCs) have the potential to differentiate into SMCs.OBJECTIVE: To induce MSCs into SMCs in vitro, and investigate the influence of the differentiated SMCs or cell factors on MSCs differentiation.DESIGN: Controlled experiment in vitro with repeated observation and measurement based on cells.SETTING: Department of Cardiology, First Hospital of Xi'an Jiaotong University.MATERIALS: The experiment was accomplished in the Laboratory of Cardiology, First Hospital of Xi'an Jiaotong University between May 2003 and May 2004. SD rats of either gender were provided by the Animal Center of Xi'an Jiao Tong University, 60-80 g, 90-110 g. The following antibodies were used: Mouse anti human SM-α-actin (NeoMarkers),Mouse anti human Calponin (NeoMarkers), TRITC-coupled goat anti mouse IgG antibody (SBA). Mouse anti rat CD34 conjugated FITC (Santa Cruz), Mouse anti rat CD71 conjugated FITC (Oxford Biotechnology), Mouse anti rat anti-CD90 conjugated PE (Oxford Biotechnology). Lipofectamine 2000 (Invitrogen). PEGFP-N3 (the laboratory).METHODS: Bone marrow mesenchymal stem cells were obtained from rat bone marrow by using percoll density gradient centrifugation. SMCs were isolated by using tissue explantation method. Flow cytometer was used to detect the immunofluorescence stain. Then MSCs and SMCs were identified. MSCs were transfected with pEGFP-N3 by Lipofectamine 2000, while untransfected MSCs were taken as controls. Conditioned culture of MSCs and SMCs: ①MSCs at passage 3 were seeded on chamber slides in a 12-well culture plate. The medium was DMEM containing 0%, 5%,7.5% fetal bovine serum (FBS) and SMCs conditioned medium containing 0%, 5%, 7.5% FBS, respectively. The cells were cultured for 10-14 days and immunofluorescence analysis was performed by using monoclonal antibodies against SM-α-actin, calponin.②Indirect co-culture of MSCs with SMCs were established using a semi-permeable membrane cell culture insert. The inserts were plated into culture well. SMCs were cultured on the inside of inserts while MSCs were added to the outside of inserts, respectively. MSCs were culture alone in medium containing 3%, 7.5% FBS and immunofluorescence analysis was performed by using monoclonal antibodies against SM-α-actin, calponin.③MSCs were transfected with pEGFP-N3. After 24 hours, the MSCs were cocultivated with SMCs at an equal density for 7-14 days.As a control, MSCs were cultured alone. MSCs co-cultured were stained with antibodies against calponin, SM-α-actin. MAIN OUTCOME MEASURES: ①Identification of MSCs by floe cytometer.②cytoplasmic antigen expression of SMCs. RESULTS: ①Immunofluorescence analysis showed that MSCs expressed SM-α-actin, but did not express calponin. As a control, SMCs expressed both SM-α-actin and calponin.②Flow cytometry showed that MSCs expressed CD71 of low level, CD90 of high level and no expression of CD34. ③The MSCs transfected with green fluorescence protein continued to express for 2-3 weeks. ④MSCs grew well in SMCs conditioned medium or different concentrations of FBS. Cell growth was FBS concentration dependent in indirect co-culture system of MSCs and SMCs. Several double-positive cells in direct co-culture system were detected enhanced green fluorescence protein and antibodies against calponin, SM-α-actin. CONCLUSION: ①SMCs conditioned medium and cell factor only promote MSCs growth and cytoplasmic granules increase. But these do not induce MSCs differentiate into SMCs. ②The cell-to-cell contact is essential for MSCs differentiation to SMCs.

THE EFFECT OF ACUTE MYOCARDIUM ISCHEMIC ON HEART FUNCTION OF PREGNANCY RAT / 药物分析学报

Objective To investigate the effect of acute myocardium ischemic on heart function of pregnancy rat.Methods 13 female SD rats and 6 early pregnancy rats were divided into normal group, unpregnant group with acute myocardial infarction and early pregnant group with acute myocardial infarction. The anterior branch of the left coronary artery was ligated. 3 weeks later, Image 1.31 software was used to measure areas of myocardial infarction,and to evaluate hemodynamics of heart with powerLAB4.12, and cardiac tissues were stained with Massion. Results Compared with unpregnant group with acute myocardial infarction , the early pregnant group with acute myocardial infarction had less myocardial infarction area (28. 86% vs. 36. 8%), and had a higher left ventricle end systolic pressure, ±dp/dt max, and lower left ventricle end diastolic pressure. Massion stain showed the amount of collagen of the lesion was less in the early pregnant group with acute myocardial infarction than that in unpregnant group.Conclusion The early pregnant group with acute myocardial infarction had better heart contractive and diastolic function.

CORRELATIONS BETWEEN BLOOD PRESSURE AND BODY WEIGHT, SERUM LEPTIN IN HIGH CALORIE DIET-INDUCED OBESE RATS / 药物分析学报

Objective To examine the change of body weight (BW) and blood pressure (BP) in obese rats, clarify relationships between BP and BW and other factors. Methods Male Spraque-Dawley rats were fed either with normal diet (ND) or high calorie diet (HC) for 20 weeks. BW and BP of tail artery were observed biweekly and tetraweekly respectively; serum leptin and fasting insulin (FINS) were detected by enzyme-linked immunoadsordent assay (ELISA) and radioimmunoassay (RIA) respectively. Fasting plasma glucose (FPG) and free fatty acid(FFA) were measured by conventional means. Results BW, abdominal fat weight (AFW), ratio of abdominal fat weight to body weight (RF/W), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum levels of leptin and FINS, FPG, FFA increased in the HD group after 20 weeks diet intervention (P＜0.05 or P＜0.01). SBP was strongly correlated with BW, leptin, FINS and FFA (P＜0.05), DBP was correlated with FFA (r=0.47, P＜0.05). In addition, leptin was positively correlated with BW, AFW, RF/W, FINS and FFA (P＜0.05 or P＜0.01). Conclusion In this study of high calorie-diet induced rats, the gain of BW is accompanied by increased BP. The obese rats have hyperleptinemia, hyperinsulinemia, hyperglycemia and dyslipidemia which may have important effects on the development of obesity-related hypertension. RF/W is the key factor in which affect serum leptin level.