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Objective To observe the intervention effect of Schisandrin B (Sch B) on cisplatin induced acute kidney injury (AKI) in mice and its possible mechanism.Methods Twenty-five BALB/c mice were randomly divided into blank control group, model group, low and high dose of Sch B intervention groups and Sch B control group. Olive oil with Sch B was administered by gavage at the dose of 20 mg/kg or 100 mg/kg for low and high dose of Sch B intervention groups respectively; olive oil with Sch B 100 mg/kg was applied by gavage to the Sch B control group; the same volume of olive oil was perfused into the gastric cavity in the blank control group and model group; the above measures in various groups were consecutively used for 5 days. On the 3rd day of the experiment, AKI mice model was established by intraperitoneal injection of cisplatin (20 mg/kg) once and the same measure was given to the low and high dose of Sch B intervention groups; 1 mL/kg normal saline was injected into the peritoneal cavity in the bland control group and Sch B control group. At the end of the experiment, the serum creatinine (SCr) level was determined; apoptosis of renal tubular epithelial cells were detected by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay; the morphological changes of renal tubular epithelial cells were observed by hematoxylin eosin (HE) staining, and renal tubular injury score was evaluated; p53 protein content in the kidney tissue was measured by immunohistochemical analysis; furthermore, expressional level of p53 protein in renal tissue was tested by Western Blot.Results Compared with the blank control group, the level of SCr (μmol/L: 86.77±10.97 vs. 14.37±0.81), renal tubular injury score (9.67±1.20 vs. 1.00±0.45), the count of apoptotic renal tubular epithelial cells (cells/200 power field: 20.00±2.13 vs. 2.30±0.40) in the model group were all increased (P < 0.05 orP < 0.01), and p53 protein content (cells/400 power field: 13.40±2.66 vs. 57.30±3.82), and the expression of p53 protein [absorbency (A value) ratio: 0.79±0.09 vs. 1.42±0.09] in model group were decreased (bothP < 0.01). Compared with the model group, in the low and high dose Sch B intervented groups, the level of SCr (μmol/L: 21.98±5.52 and 37.45±5.04), renal tubular injury score (5.67±0.76 and 6.17±0.65), the count of apoptotic renal tubular epithelial cells (cells/200 power field: 10.60±1.05 and 11.60±1.45) were all reduced (allP < 0.01), p53 protein content (cells/400 power field: 42.40±3.67 and 45.90±2.31) and the expression of p53 protein (A value ratio: 1.36±0.16 and 1.25±0.11) were increased (bothP < 0.01). HE staining showed the pathological changes of renal tubules, such as renal tubular epithelial cellular fusion, vacuolization, cast formation, and tubular lumen constriction/dilation in model group; the pathological changes in kidney tissues observed in low and high dose Sch B intervention groups were milder than those in model group.Conclusion Sch B plays a beneficial role in the cisplatin induced AKI in mice, and its protective effect might be mediated by decreasing SCr, regulating p53 protein expression level and inhibiting the apoptosis of renal tubular epithelial cells.
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<p><b>OBJECTIVE</b>To assess the cardiopulmonary exercise testing (CPET) derived performance of oxygen uptake and ventilation efficiency parameters, including oxygen uptake efficiency plateau (OUEP) , oxygen uptake efficiency slope (OUES), V·E/V·CO2 slope and lowest V·E/V·CO2, in patients with end-stage chronic heart failure (CHF) and evaluate their clinical value on monitoring cardiac function and hemodynamic status.</p><p><b>METHODS</b>A total of 26 end-stage CHF patients considered for heart transplantation were enrolled in this study. CPET, echocardiography and invasive hemodynamic examinations with Swan-Ganz flowing balloon catheter were performed. Correlation analysis was made between oxygen uptake and ventilation efficiency parameters from CPET and echocardiographic and hemodynamic parameters.</p><p><b>RESULTS</b>OUEP and OUES showed good correlation with peak oxygen consumption (peak V·O2) (r = 0.535, P < 0.01;r = 0.840, P < 0.001). In end-stage CHF patients, the slope of OUEP with respect to peak V·O2 is about 32, but the slope of OUES with respect to peak V·O2 is only about 2. The difference was 16 times. The change of OUEP was more sensitive and significant than those of OUES and peak V·O2 (P < 0.05). OUEP, peak V·O2 (%pred), V·E/V·CO2 slope and lowest V·E/V·CO2 were all correlated well with non-invasive hemodynamic parameters peak cardiac output (r = 0.535, P < 0.01; r = 0.652, P < 0.001; r = -0.640, P < 0.001; r = -0.606, P = 0.001 respectively) and peak cardiac index (r = 0.556, P < 0.01;r = 0.772, P < 0.001; r = -0.641, P < 0.001; r = -0.620, P < 0.001 respectively) derived from CPET, but not correlated with invasive hemodynamic parameters cardiac output and cardiac index at rest (P > 0.05). Both peak V·O2 (%pred) and V·E/V·CO2 slope were significantly correlated with invasive hemodynamic parameters systolic pulmonary arterial pressure (r = -0.424, P < 0.05; r = 0.509, P < 0.01) and mean pulmonary arterial pressure (r = -0.479, P < 0.05; r = 0.405, P < 0.05). Peak V·O2 (%pred) was also significantly correlated with pulmonary capillary wedge pressure (r = -0.415, P < 0.05), and V·E/V·CO2 slope was significantly correlated with pulmonary vascular resistance (r = 0.429, P < 0.05).</p><p><b>CONCLUSIONS</b>The oxygen uptake and ventilation efficiency parameters derived from CPET, including peak V·O2, OUEP, lowest V·E/V·CO2 and V·E/V·CO2 slope etc, are objectively monitoring and evaluating cardiac function and hemodynamic status. And they are useful for optimizing clinical management of patients with end-stage CHF.</p>
Subject(s)
Humans , Cardiac Output , Chronic Disease , Exercise Test , Heart Failure , Hemodynamics , Oxygen , Metabolism , Oxygen Consumption , Pulmonary Wedge PressureABSTRACT
Objective To explore the protective effects of schisandrin B (Sch B) on hypoxia injury induced by cobaltous chloride (CoCl2) in human proximal renal tubular epithelial (HK-2) cells, and the possible mechanism thereof. Methods HK-2 cells were randomly assigned to four groups:control group (Con, cells were untreated), CoCl2 group (CoCl2, cells were treated with 600μmol/L CoCl2 for 24 h), Sch B pretreat group (CoCl2+Sch B, cells were pretreated with 1μmol/L and 10μmol/L Sch B for 2 h) and Sch B group (Sch B, cells were treated with 1μmol/L and 10μmol/L Sch B for 2 h). CCK-8 kit was used to detect the cell viability of four groups. Flow cytometry was used to detect the apoptotic rate of four groups. The protein expression of hypoxia-inducible factor 1α(HIF-1α) was assessed by Western blot assay. The expressions of HIF-1α and inducible nitric oxide synthase (iNOS) mRNA were determined by RT-PCR. Results Compared with the control group, after treated with 600 μmol/L CoCl2, the cell viability was decreased, and the apoptosis was increased, the expressions of HIF-1α and iNOS mRNA were up-regulated in HK-2 cells. There was no significant difference in the expression of HIF-1α mRNA between control group and CoCl2 group. Compared with the CoCl2 group, after pretreated with 1μmol/L and 10μmol/L Sch B, the cell viability was increased and the apoptosis was decreased, the expressions of HIF-1α and iNOS were down-regulated in HK-2 cells. There were no significant differences in the cell viability and apoptotic rate between control group and Sch B group. Conclusion Pretreatment with Sch B can reduce the apoptosis of HK-2 cells by inhibiting the expression of HIF-1α and iNOS mRNA, which shows protective effects on hypoxia injury.
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<p><b>OBJECTIVE</b>To observe oxygen uptake efficiency plateau (OUEP, i.e.highest V˙O2/V˙E) and carbon dioxide output efficiency (lowest V˙E/V˙CO2) parameter changes during exercise in normal subjects.</p><p><b>METHODS</b>Five healthy volunteers performed the symptom limited maximal cardiopulmonary exercise test (CPET) at Harbor-UCLA Medical Center. V˙O2/V˙E and V˙E/V˙CO2 were determined by both arterial and central venous catheters. After blood gas analysis of arterial and venous sampling at the last 30 seconds of every exercise stage and every minute of incremental loading, the continuous parameter changes of hemodynamics, pulmonary ventilation were monitored and oxygen uptake ventilatory efficiency (V˙O2/V˙E and V˙E/V˙CO2) was calculated.</p><p><b>RESULTS</b>During CPET, as the loading gradually increased, cardiac output, heart rate, mixed venous oxygen saturation, arteriovenous oxygen difference, minute ventilation, minute alveolar ventilation, tidal volume, alveolar ventilation and pulmonary ventilation perfusion ratio increased near-linearly (P < 0.05-0.01, vs.resting); arterial oxygen concentration maintained at a high level without significant change (P > 0.05); stroke volume, respiratory rate, arterial partial pressure of carbon dioxide, arterial blood hydrogen ion concentration and dead space ventilation ratio significantly changed none-linearly (compare resting state P < 0.05-0.01).OUE during exercise increased from 30.9 ± 3.3 at resting state to the highest plateau 46.0 ± 4.7 (P < 0.05 vs.resting state), then, declined gradually after anaerobic threshold (P < 0.05-0.01, vs.OUEP) and reached 36.6 ± 4.4 at peak exercise. The V˙E/V˙CO2 during exercise decreased from the resting state (39.2 ± 6.5) to the minimum value (24.2 ± 2.4) after AT for a few minutes (P > 0.05 vs.earlier stage), then gradually increased after the ventilatory compensation point (P < 0.05 vs.earlier stage) and reached to 25.9 ± 2.7 at peak exercise.</p><p><b>CONCLUSIONS</b>Cardiac and lung function as well as metabolism change during CPET is synchronous.In the absence of pulmonary limit, appearing before and after anaerobic threshold, OUEP and lowest V˙E/V˙CO2 could be used as reliable parameters representing the circulatory function.</p>
Subject(s)
Humans , Arteries , Blood Gas Analysis , Blood Pressure , Carbon Dioxide , Metabolism , Cardiac Output , Exercise , Physiology , Exercise Test , Heart , Heart Rate , Hemodynamics , Lung , Oxygen , Metabolism , Oxygen ConsumptionABSTRACT
Objective To explore the effect of schisandra chinensis fruit ethanol extract on nephrin and desmin ex-pression in adriamycin(ADR) induced podocyte injury in vitro. Methods Conditionally immortalized mouse podocytes were treated with ADR for 24 h in vitro, then the medium was changed to medium with SE(250 mg/L)for 24 h. Podocytes were di-vided into four groups:control group,model group, SE intervention group and SE group. The expression of nephrin in podo-cytes was detected by immunofluorescence. Western Blot was employed to assess nephrin and desmin expression. Transcrip-tion level of nephrin and desmin were determined by qRT-PCR. Results Nephrin expression was distributed along the cell membrane in linear or granular pattern in control group and SE group. Fluorescence intensity in model group was lower than that of control group SE group and SE intervention group. There was no significant difference of nephrin and desmin protein and mRNA level between control group and SE group. Compared with the model group, protein and mRNA level of nephrin was lower than that of control group and SE intervention group. The protein expression and mRNA transcription of desmin in model group was higher than those in control group and SE intervention group (P＜0.05). Conclusion SE(250 mg/L)has no harmful effect on the podocytes in vitro. SE can protect the podocytes from damage by adriamycin in vitro. SE not only up-regulate the expression of nephrin, but also down-regulate of desmin expression.
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Objective To explore the correlation between heart rate recovery after exercise test and disease severity in patients with chronic obstructive pulmonary disease(COPD)and assess its impact on the exercise capacity of COPD patients.Methods Arterial blood gas analysis, pulmonary lung function test and cardiopulmonary exercise testing were performed in 60 patients with stable COPD and 50 healthy volunteers.Based on the heart rate recovery after exercise test, COPD patients were divided into normal heart rate recovery group(n =41)and abnormal heart rate recovery group(n =19).Results The COPD patients had lower exercise capacity(peak oxygen uptake as percentage of predicted value, peak VO2％ pred)(66 ± 15vs.89±11, P＜0.01), peak heart rate [(134±21)vs.(149±13)beats/min, P＜0.01], heart rate recovery[(18 ± 9)vs.(27 ± 10)beats/min, P ＜ 0.01] and higher resting heart rate [(83 ± 13)vs.(77 ± 13)beats/min, P ＜0.01] than the controls.Compared with normal heart rate recovery group, forced expiratory volume in one second as percentage of predicted(FEV1 ％ pred)and exercise capacity decreased more significantly in abnormal heart rate recovery group(38 ± 15 vs.52 ± 16, P＜0.05 and 57 ± 12 vs.71 ±14, P ＜0.01).Heart rate recovery was significantly correlated with FEV1％ pred and peak V O2％ pred(r=0.42, P ＜ 0.01 and r =0.52, P ＜ 0.01).Multivariate regression analysis showed that heart rate recovery and FEV1 ％ pred could be used as independent predictors of exercise capacity in COPD patients.Conclusion In COPD patients, heart rate recovery is correlated with the degree of disease severity and it may be an independent predictor of exercise capacity.