RESUMO
BACKGROUND@#Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions.@*METHODS@#Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730).@*RESULTS@#Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly.@*CONCLUSION@#These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.
Assuntos
Animais , Camundongos , Linfócitos T CD4-Positivos , Diferenciação Celular , Endotoxinas/toxicidade , Citometria de Fluxo , Transdução de Sinais , Timócitos , TimoRESUMO
Objective: To investigate the correlation between the biomarkers and left ventricular remodeling (LVR) in patients after acute myocardial infarction (AMI). Methods: 220 patients with AMI who were admitted in the Department of Cardiology of the Shanghai Sixth People's Hospital from January 1st, 2015 to January 1st, 2016 and received successful primary percutaneous coronary intervention were included in this study sequentially. AMI patients due to right coronary artery were excluded. LVR after AMI was defined as more than 20% increase of the left ventricular end diastolic volume (LVEDV) measured by echocardiogram in 1-year-follow-up compared with LVEDV at admission. Patients were divided into LVR group and non-LVR group. The differences of myocardial injury markers and inflammatory factors between the two groups were compared, and the correlation between LVR and the biomarkers was analyzed. Results: Compared with the non-LVR group, the cTnI (serum cardiac troponin I), CKMB (creatine kinase MB) and myoglobin levels at admission and peaks, as well as neutrophil to monocyte ratio and neutrophil to lymphocyte ratio (NLR) in the LVR group were increased significantly (all P<0.05). There was no significant difference in proBNP (brain natriuretic peptide precursor) and BNP levels between the two groups. Logistic regression analysis showed that cTnI and NLR at admission were correlated well with LVR. ROC curve analysis showed that the area under the cTnIadmission curve (AUC) was 0.704, and the sensitivity and specificity of cTnIadmission to predict LVR after AMI were 69.2% and 64.3% respectively, when 9.14 μg/L was chosen as the cut-off point. The area under the NLR curve (AUC) was 0.664, and the sensitivity and specificity of NLR were 70.6% and 60.2% respectively, when 5.87% was chosen as the cut-off point. Conclusion: The increased levels of cTnI and NLR at admission in patients with AMI are independent predictors of LVR.
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Objective To explore the role of cine sequence of cardiac magnetic resonance (CMR) imaging in evaluating left ventricular (LV) diastolic function in patients with heart failure with preserved ejection fraction (HFpEF). Methods LV two-chamber, three-chamber, four-chamber long-axis and series of short-axis cine images were obtained from 30 patients with HFpEF (HFpEF group) and 15 cases with normal cardiac function (control group) using CMR examination. LV volume-time curve (VTC) and global strain curves were drawn. Peak filling rate and peak filling volume, global longitudinal, global radial, global circumferential peak strain and peak diastolic strain rate were compared between the two groups. Results Compared with the control group, LV remodeling index (LVRI) in the HFpEF group was significantly increased (0.86±0.15 vs 0.73±0.08, P<0.05), first peak filling rate/second peak filling rate (PFR1/PFR2) was significantly decreased or even inverted (0.74 ±0.14 vs 1.43±0.34, P=0.001), and first filling volume (FV1) and FV1/total filling volume (FV1/FV) were significantly decreased (26.24±9.74 vs 31.30±5.17, P<0.05; 0.59±0.05 vs 0.69±0.03, P<0.05). Global longitudinal peak strain (GLS) ([-14.96±1.79]% vs[-20.96±0.84]%,P<0.01), global longitudinal diastolic peak strain rate (0.65±0.16 vs 1.29±0.27, P<0.05), global radial diastolic peak strain rate (-2.23±0.71 vs -3.80±1.13, P<0.05) and global circumferential diastolic peak strain rate (GDCSR) (1.02±0.14 vs 1.77±0.63, P<0.05) in the HFpEF group were significantly decreased versus control group. Conclusion LVRI, PFR1/PFR2, FV1 and GDCSR obtained by CMR can accurately evaluate the changes of LV diastolic function in HFpEF, which may play important roles in the diagnosis and treatment of HFpEF.