Objective To investigate the effects of simvastatin on monocrotaline-induced pulmonary hypertension in rats, and explore the potential mechanism of simvastatin by blocking heme oxygenase-1( HO-1) expression. Methods 52 male Sprague-Dawley rats were randomly divided into five groups, ie. a control group, a simvastatin control group, a pulmonary hypertension model group, a simvastatin treatment group, a ZnPP ( chemical inhibitor of HO) group. Mean pulmonary arterial pressure ( mPAP) and right ventricular systolic pressure ( RVSP) were detected by right heart catheter at 5th week. Right ventricular hypertrophy index ( RVHI) was calculated as the right ventricle to the left ventricle plus septum weight. Histopathology changes of small intrapulmonary arteries were evaluated via image analysis system.Immunohistochemical analysis was used to investigate the expression and location of HO-1. HO-1 protein level in lung tissue were determined by western blot. Results Compared with the model group, simvastatin treatment decreased mPAP and RVHI significantly [ ( 35. 63 ±5. 10) mm Hg vs. ( 65. 78 ±15. 51) mm Hg,0. 33 ±0. 05 vs. 0. 53 ±0. 06, both P lt; 0. 05 ] . Moreover, simvastatin treatment partially reversed the increase of arterial wall area and arterial wall diameter [ ( 50. 78 ±9. 03 ) % vs. ( 65. 92 ±7. 19) % ,( 43. 75 ±4. 23) % vs. ( 52. 00 ±5. 35) % , both P lt; 0. 01) . In the model group, HO-1 staining was primarily detected in alveolar macrophages. Simvastatin treatment increased HO-1 protein expression significantly, especially in the thickened smooth muscle layer and alveolar macrophages. Inhibiting HO-1 expression using ZnPP resulted in a loss of the effects of simvastatin. mPAP in the ZnPP group was ( 52. 88±17. 45) mm Hg, while arterial wall area and arterial wall diameter were ( 50. 78 ±9. 03) % and ( 52. 00 ±5. 35) % , respectively. Conclusions Simvastatin attenuates established pulmonary arterial hypertension andpulmonary artery remodeling in monocrotaline-induced pulmonary hypertension rats. The effect of simvastatin is associated with HO-1.
Objective To investigative the effects of combination treatment with simvastatin and aspirin in a rat model of monocrotaline-induced pulmonary hypertension. Methods Sixty male Sprague-Dawley rats were randomly divided into a control group, a simvastatin group, an aspirin group, and a combination treatment group. The control group received monocrotaline injection subcutaneously to induce pulmonary hypertension. Simvastatin ( 2 mg/kg) , aspirin ( 1 mg/kg) , or simvastatin ( 2 mg/kg) + aspirin ( 1 mg/kg) was administered once daily to the rats of treatment groups respectively for 28 days after monocrotaline injection. Mean pulmonary arterial pressure ( mPAP) was detected by right heart catheter.Right ventricular hypertrophy index ( RVHI) was calculated as the right ventricle to the left ventricle plus septum weight. Histopathology changes of small intrapulmonary arteries were evaluated via image analysissystem. Interleukin-6 ( IL-6) level in lung tissue was determined by ELISA.Results Compared with the control group, simvastatin or aspirin decreased mPAP [ ( 34. 1 ±8. 4) mm Hg, ( 38. 3 ±7. 1) mmHg vs.( 48. 4 ±7. 8) mmHg] and increased arterial wall diameter significantly ( P lt; 0. 05) . The combination treatment group showed more significant improvement in mPAP, RVHI and pulmonary arterial remodeling compared with each monotherapy ( P lt;0. 05) . Moreover, the combination therapy had additive effects on the increases in lung IL-6 levels and the perivascular inflammation score. Conclusions Combination therapy with simvastatin and aspirin is superior in preventing the development of pulmonary hypertension. The additive effect of combination therapy is suggested to be ascribed to anti-inflammation effects.
ObjectiveTo investigate the association between serum thyroid hormone levels and prognosis for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) without thyroid disease, and explore the prognostic value of serum thyroid hormone levels for patients with AECOPD.MethodsThe clinical data of 239 hospitalized cases of AECOPD [149 males, 90 females, aged 42-92 (77.7±8.9) years] from January 2013 to November 2017 were retrospectively analyzed. Serum thyroid hormone levels including total tetraiodothyronin (TT4), total triiodothyronin (TT3), thyroid stimulating hormone (TSH), free tetraiodothyronin (FT4) and free triiodothyronin (FT3) were measured by chemiluminescence immunoassay. All patients were divided into a survival group and a death group according to the prognosis. Serum thyroid hormone levels were compared between two groups. Correlations of serum thyroid hormone levels with the occurrence of death in AECOPD patients were analyzed. The prognostic value of serum thyroid hormone levels for AECOPD patients was explored by receiveroperating characteristic (ROC) curve analysis. And the best cut-off value of serum thyroid hormone level in predicting the risk of death was calculated.ResultsSerum TT4, TT3, FT4 and FT3 levels in the survival group were significantly higher than those in the death group [TT4: (89.35±21.45) nmol/L vs. (76.84±21.33) nmol/L; TT3: (1.05±0.34) nmol/L vs. (0.72±0.19) nmol/L; FT4: (16.17±2.91) pmol/L vs. (14.45±2.85) pmol/L; FT3: (3.06±0.81) pmol/L vs. (2.24±0.72) pmol/L; all P<0.05]. The differences of serum TSH level between two groups were not statistically significant [0.98 (0.54-1.83)vs. 0.57 (0.31-1.84), P>0.05]. Spearman correlation analysis showed that serum TT4, TT3, FT4 and FT3 levels were significant correlated with the occurrence of death (r values were 0.226, 0.417, 0.220, 0.387, respectively, P<0.05). And there was no significant correlation between serum TSH level and the occurrence of death (P>0.05). ROC curve analysis was done between serum thyroid hormone levels (TT4, TT3, TSH, FT4 and FT3) and the occurrence of death in the AECOPD patients. The areas under ROC curve were 0.659, 0.793, 0.588, 0.655 and 0.772, respectively. Serum TT3 was the best indicator for predicting the occurrence of death. When serum TT3 level was 0.85nmol/L, the Youden index was the highest (0.486), with a sensitivity of 70.2%, and a specificity of 78.3%. It was the best cut-offl value of serum TT3 to predict the risk of death in AECOPD patients.ConculsionsSerum thyroid hormone levels are significant associated with the prognostic for AECOPD patients. There is certain value of serum thyroid hormone levels in prognostic evaluation of AECOPD patients.
ObjiectiveTo explore the efficacy and safety of ketogenic diet therapy (KDT) in the rapidly progressive stage of childhood developmental epileptic encephalopathy Dravet syndrome (DS). Methods The clinical data of all patients who added KDT in the Children’s Hospital of Fudan University from 2011 to 2022 were retrospectively collected, and the age of <6 years was used as the criterion for the rapid progression of the disease. The clinica data, genotype and the efficacy of KDT were analyzed in DS patients who met the criteria. Results A total of 32 patients met the criteria for rapid disease progress, including 22 males and 10 females. The age at onset was (5.69±2.10) months. All patients had multiple seizure phenotypes and monthly seizures despite reasonable Antiseizure medications treatment. After 3, 6, 12, and ≥24 months, 93.8% (30/32), 87.5% (28/32), 53.1% (17/32), 34.4% (11/32) remained on the KDT, while 76.7% (23/30), 75.0% (21/28), 70.6% (12/17), 54.5% (6/11) showed >50% reduction in seizure. Status epileptius (SE) was reduced by 100% at 3 months, 71.0% at 6 months, 86.0% at 12 months. After 12 months, 14 patients experienced efficacy degradation. After 3 months, the EEG background rhythm showed improvement in 75.0% patients, interictal epileptic discharges was decreased in 54.5% patients and cognitive function was improved in 78.6% patients. At the initial stage of KDT, 62.5% (20/32) patients had transisent adverse reactions, including diarrhea, vomiting, fatigue, lethargy, hypoglycemia, and metabolic acidosis, but no mid- and long-term adverse reactions were found. ConclusionKDT is an efficective and safe treatment for DS. KDT can effectively control seizures, reduce the incidence of Status SE and shorten the duration of SE. With the prolongation of the KDT course, some patients experienced a degraded effect. KDT can improve abnormal EEG and cognitive function in DS patients. Pharmoco-resistant DS patients are suggested to receive KDT in the early stage of disease progression.