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Objective To investigate the effects of overexpression of nuclear factor E2 related factor 2 (Nrf2) protein on placental oxidative stress and fetal cardiac function in pregnant mice with gestational diabetes mellitus. Methods Thirty-six pregnant mice were randomly divided into four groups: control group, model group, pcDNA group and Nrf2 group. Pregnant mouse model of gestational diabetes was establish by intraperitoneal injection of streptozotocin (STZ); mice in each group were transfected with corresponding adenovirus or saline. RT-PCR and Western blotting were performed to detect the expression levels of Nrf2 mRNA and protein in the placenta of pregnant mice. Fasting blood glucose was measured, uterine index, total number of fetuses and abortion rate were calculated. The placental superoxide dismutase (SOD) activity, contents of reduced glutathione (GSH) and malondialdehyde (MDA) in pregnant mice were detected. HE staining was used to observe the pathological changes of liver and kidney tissue of pregnant mice. The protein expression level of Nrf2 in the heart tissue of offspring mice was detected by Western blotting. The heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (LVEF) and shortening fraction (FS) of offspring mice were measured; ELISA was performed to detect the serum contents of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI) and myoglobin (MB) of offspring mice. HE staining was used to observe the pathological changes of myocardium in offspring mice. Results Compared with the control group, the Nrf2 mRNA level, Nrf2 protein expression level, SOD activity and GSH content, as well as the HR, LVSP, LVEF and FS of the offspring mice were obviously reduced in model group and pcDNA group (P<0.05); the fasting blood glucose, abortion rate and MDA content in pregnant mice, as well as the contents of CK-MB, MB and cTnI in offspring mice increased, while the uterine index and total fetal number decreased significantly (P<0.05); while the above indicators showed no significant difference in Nrf2 group. Compared with the model group, the Nrf2 mRNA level and protein expression level, SOD activity, GSH content, as well as the HR, LVSP, LVEF and FS of offspring increased significantly in Nrf2 group; the fasting blood glucose, abortion rate and MDA content in pregnant mice, as well as the contents of CK-MB, MB and cTnI in offspring mice decreased, while the uterine index and total fetal number increased significantly (P<0.05); while the above indicators showed no significant difference in pcDNA group. In addition, HE staining results showed that Nrf2 overexpression reduced the pathological damage of liver and kidney tissues of diabetic pregnant mice and the myocardial damage of the offspring mice. Conclusion Over-expression of Nrf2 protein can alleviate placental oxidative stress in gestational diabetic pregnant mice and maintain the cardiac function of the offspring mice.
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Abstract Objective: Mucopolysaccharidosis is a rare genetic disease characterized by the intralysosomal deposition of glycosaminoglycans. Cardiovascular impairment is a common feature. Cardiac signs and symptoms are underestimated due to the disease involvement in other organs. Enzyme replacement therapy can be used in mucopolysaccharidosis I, II, IV, and VI. Thus, the knowledge about the use of new echocardiography tools is relevant to improve the care of this population. This study aimed to describe left ventricular function assessment by conventional echocardiography and left ventricular global longitudinal strain analysis and compare the alterations in patients receiving enzyme replacement therapy and who had different ages at the start of therapy. Method: Outpatient-based descriptive study. The patients were submitted to conventional echocardiography and left ventricular global longitudinal strain measurement. Results: Sixteen patients were evaluated; median age of 14.2 years (SD = 5.2 years). Left ventricular hypertrophy was found in nine patients (56.2%). All patients had preserved left ventricular systolic function (Simpson and Teichholz). Nine (56.2%) patients showed alterations in left ventricular global longitudinal strain. The study showed a positive association between left ventricular hypertrophy and alteration in the left ventricular global longitudinal strain, and late start of enzyme replacement therapy and alteration in the left ventricular global longitudinal strain. Conclusion: Echocardiographic alterations in patients with mucopolysaccharidosis were frequently observed, especially alterations in the left ventricular geometry and subclinical dysfunction. Patients who had a late enzyme replacement therapy start showed an association with worse left ventricular global longitudinal strain values, reinforcing the need for early diagnosis and treatment. The use of new echocardiographic tools may improve the follow-up of these patients.
Resumo Objetivo: A mucopolissacaridose é uma doença genética rara, caracterizada por depósito intralisossômico de glicosaminoglicanos. O comprometimento cardiovascular é frequente. Sinais e sintomas cardíacos são subestimados pelo envolvimento da doença em outros órgãos. A terapia de reposição enzimática pode ser usada em mucopolissacaridose I, II, IV e VI. Assim, o conhecimento da aplicação de novas ferramentas de ecocardiografia é relevante para melhorar a assistência dessa população. Este estudo visou descrever a função do ventrículo esquerdo pelo ecocardiograma convencional e pela análise do strain global longitudinal do ventrículo esquerdo e comparar as alterações em pacientes que fazem uso da terapia de reposição enzimática e que tiveram idades distintas de início da terapia. Método: Estudo descritivo de base ambulatorial. Os pacientes foram submetidos à ecocardiografia convencional e medida do strain global longitudinal do ventrículo esquerdo. Resultados: Foram avaliados 16 pacientes; mediana de 14,2 anos (desvio: 5,2 anos). Hipertrofia do ventrículo esquerdo foi encontrada em nove pacientes (56,2%). Todos os pacientes tiveram função sistólica do ventrículo esquerdo preservada (Simpson e Teichholz). Nove (56,2%) pacientes apresentaram alteração no strain global longitudinal do ventrículo esquerdo. O estudo mostrou associação positiva entre hipertrofia do ventrículo esquerdo e alteração no strain global longitudinal do ventrículo esquerdo e início tardio da terapia de reposição enzimática e alteração no strain global longitudinal do ventrículo esquerdo. Conclusão: Alterações ecocardiográficas em pacientes com mucopolissacaridose foram frequentes, especialmente alterações na geometria e disfunção subclínica do ventrículo esquerdo. Pacientes que iniciaram tardiamente a terapia de reposição enzimática apresentaram associação com piores valores de strain global longitudinal do ventrículo esquerdo, o que reforça a necessidade do diagnóstico e tratamento precoces. O uso de novas ferramentas de ecocardiografia pode melhorar o acompanhamento desses pacientes.
Subject(s)
Humans , Male , Female , Child , Adolescent , Mucopolysaccharidoses/complications , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/diagnostic imaging , Myocardium/pathology , Echocardiography/methods , Cross-Sectional Studies , Mucopolysaccharidoses/drug therapy , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/drug therapy , Enzyme Replacement TherapyABSTRACT
Objective To explore the clinical effect of trimetazidine in the treatment of coronary heart disease(CHD)patients with heart failure.Methods 80 CHD patients with heart failure cases in our hospital from April 2015 to January 2016 were selected as the research subjects.According to the random lottery method,they were divided into two groups.The control group(n =40)adopted routine comprehensive treatment,the treatment group(n =40)was given trimetazidine on the basis of conventional treatment.The clinical curative effect and heart function index before and after the treatment,exercise tolerance and the change of vascular endothelial function were compared between the two groups.Results The total effective rate of the treatment group was 97.50%(39 /40),which was higher than 77.50%(31 /40)of the control group(χ2 =3.98,P =3.98).After treatment,the systolic blood pressure, left ventricular end systolic diameter and left ventricular end -diastolic diameter in the treatment group were less than the control group,while the left ventricular ejection fraction was greater than the control group,the differences between the two groups were statistically significant (all P 0.05 ).The 6 min walking distance of the treatment group after treatment was (375.67 ±28.48)m,which of the control group was (306.18 ±25.71)m,the difference was statistically significant (t =11.451,P =11.451),and the 6 min walking distance before treatment had no statistically significant difference (t =0.013,P =0.013).In the treatment group after treatment,the vascular endothelial function index was (2.32 ± 0.36 )mg/L,which of the control group was (2.95 ±0.16 )mg/L,the difference was statistically significant (t =10.114,P =10.114),while the two groups before treatment had no statistically significant difference in endothelial function index (t =0.126,P =0.126).Conclusion The clinical effect of trimetazidine in the treatment of CHD patients with heart failure is sure,and it can effectively relieve symptoms of heart failure patients,improve the cardiac function,improve their exercise tolerance,which can be used as an ideal drug in CHD patients with heart failure.
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BACKGROUND AND OBJECTIVES: An increased pulse wave velocity (PWV) and a non-dipping pattern in hypertensive patients have been shown to be associated with an excess of target organ damage. The relationship between the PWV and circadian variation of blood pressure (BP) (dipper or nondipper) were sought, and also the LV diastolic function between dipper and nondipper patients compared. SUBJECTS AND METHODS: 44 hypertensive subjects, who had never been treated, were enrolled (mean age: 48+/-12 yrs, men: 29). The following procedures were undertaken. 1) 24 hour ambulatory BP monitoring; 2) echocardiography for LV geometry, LV mass index (LVMI), LV systolic and diastolic functions, including tissue Doppler and aortic PWV. The patients were divided into two groups with respect to their ambulatory BP profiles, i.e., dipper and nondipper. The PWV, LV geometry and diastolic functions were compared between dipper and nondipper patients, and the relationship between the PWV and diastolic function analyzed in all patients. RESULTS: Twenty (45%) were nondipper patients. There were no significant differences in the LV geometry, LVMI and PWV between dipper and nondipper patients (PWV; 8.8+/-3.1 vs. 8.6+/-3.3 m/sec, p>0.05). In all patients, the PWV was related to the deceleration time (r=0.34, p=0.03) and the mitral E/A (r=-0.31, p=0.02) and mitral Em/Am ratios obtained by the tissue Doppler echocardiography (r=-0.31, p=0.03). The proportion with diastolic dysfunction was higher in the nondipper than the dipper patients (21 vs. 50%, p<0.01). There was a significant relation between the PWV and Em (r=-0.45, p=0.047) in the nondipper, but not in the dipper. CONCLUSION: Prolonged exposure to high BP (nondipper) was not related with increased aortic stiffness in never treated hypertensive patients. The PWV was closely related with LV diastolic dysfunction in nondipper patients.