RESUMEN
To study the effect of sinomenine (Sin) on isoproterenol (Iso, ß-agonist)-induced cardiac hypertrophy (CH), we set up four mouse groups: control, Iso model, Iso+metoprolol (Met, ß blocker) 60 mg/kg and Iso+Sin 120 mg/kg. CH was induced by Iso (s.c. for 28 days) in mice, and Sin or Met were orally administered by gavage for 28 days in total. Left ventricular diastolic anterior wall thickness (LVAWd), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular ejection fraction (LVEF), and short axis shortening (FS) were measured by echocardiography. Malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were measured by commercial kits. Lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) were measured by ELISA kits. Histological changes were observed using hematoxylin-eosin (HE) and Masson staining. Protein level of nuclear transcription factor-kappa B (NF-κB) was detected by immunohistochemistry. Compared with the control group, LVAWd, Left ventricular weight index (LVWI) and myocardial fibrosis of the Iso model group significantly increased, as well as NF-κB, LDH, MDA, TNF-α, and IL-1ß levels. However, the activity of T-SOD decreased. Compared with the Iso model group, LVWI of Iso model+Sin or Iso model+Met group was improved, LVAWd, LVPWd and myocardial fibrosis decreased, and NF-κB, LDH, MDA, TNF-α and IL-1ß levels decreased. T-SOD activity also increased. This study reveals that Sin inhibits the activation of NF-κB, lowers the levels of TNF-α and IL-1ß, has anti-oxidative stress effect and inhibits myocardial inflammation in mouse heart, thereby demonstrating its efficacy in preventing Iso induced CH.
Asunto(s)
Cardiomegalia , Morfinanos , FN-kappa B , Factor de Necrosis Tumoral alfa , Animales , Cardiomegalia/inducido químicamente , Fibrosis , Isoproterenol/toxicidad , Ratones , Morfinanos/farmacología , FN-kappa B/metabolismo , Volumen Sistólico , Superóxido Dismutasa/efectos adversos , Factor de Necrosis Tumoral alfa/efectos adversos , Función Ventricular IzquierdaRESUMEN
OBJECTIVES: The aim of this study was to determine the therapeutic effects of tetrahydropalmatine (Tet) on disseminated intravascular coagulation (DIC) by exploring the role of Tet using a lipopolysaccharide (LPS)-induced DIC model. Methods/Materials: We established a mouse DIC model by injecting LPS. Hematoxylin-eosin (HE) staining was performed to detect liver and kidney damage. Blood samples were obtained to determine liver and kidney injury indexes, coagulation indexes, and inflammatory cytokines. An in vitro cell inflammation model was also established. Tumor necrosis factor-α (TNF-α) levels and nuclear factor kappa B (NF-κB) signaling pathway activation were determined by western blot. RESULT: Tet ameliorated the damage to organ tissues, improved coagulation indexes, and reduced the inflammatory cytokine production in LPS-induced mouse DIC. Tet also inhibited TNF-α expression by suppressing NF-κB signaling pathway activation in an in vitro LPS model using RAW 264.7 macrophages. CONCLUSIONS: Tet has a mitigating and therapeutic effect on the LPS-induced DIC model via anticoagulant and anti-inflammatory effects, showing its potential as an adjunct to DIC treatment.
Asunto(s)
Alcaloides de Berberina , Coagulación Intravascular Diseminada , Animales , Alcaloides de Berberina/farmacología , Alcaloides de Berberina/uso terapéutico , Coagulación Intravascular Diseminada/inducido químicamente , Coagulación Intravascular Diseminada/tratamiento farmacológico , Lipopolisacáridos/toxicidad , Ratones , FN-kappa B/genética , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: To investigate the relationship between gastrointestinal dysfunction and both severity and prognosis in patients with heatstroke ( HS ). METHODS: A retrospective analysis was conducted. Clinical data from 39 patients with HS seeking for treatment in Department of Critical Care Medicine of Chinese PLA General Hospital from January 2013 to September 2014 were enrolled. The patients were divided into two groups: gastrointestinal dysfunction group and non-gastrointestinal dysfunction group. The acute physiology and chronic health evaluation II ( APACHEII) score within 24 hours of admission and 28-day mortality were compared between two groups. In gastrointestinal dysfunction group, the gastrointestinal dysfunction score, the duration days of gastrointestinal dysfunction, the length of intensive care unit ( ICU ) stay, and the duration of mechanical ventilation were collected. Pearson correlation analysis was used to analyze the relationship between gastrointestinal function and the severity of the ailment as well as the prognosis. RESULTS: Among 39 patients with HS, 32 of them showed gastrointestinal dysfunction with an incidence of 82.05%. In gastrointestinal dysfunction group, the gastrointestinal dysfunction score was 2.3±0.8, the duration of gastrointestinal dysfunction was ( 17.3±15.2 ) days, the length of ICU stay was ( 37.8±25.0 ) days, and the duration of mechanical ventilation was ( 27.8±14.0 ) days. APACHEII score in gastrointestinal dysfunction group was significantly higher than that of the non-gastrointestinal dysfunction group ( 26.30±6.00 vs. 17.40±6.00, t = 3.555, P = 0.001 ). The 28-day mortality in gastrointestinal dysfunction group was slightly higher than that of the non-gastrointestinal dysfunction group without statistically significant difference [ 43.75% ( 14/32 ) vs. 14.29% ( 1/7 ), P = 0.216 ]. It was shown by Pearson analysis that gastrointestinal dysfunction score was positively correlated with APACHEII score ( r = 0.727, P = 0.000 ), and the duration of gastrointestinal dysfunction was positively correlated with the length of ICU stay ( r = 0.797, P = 0.000 ) and the duration of mechanical ventilation ( r = 0.634, P = 0.000 ). CONCLUSIONS: The results suggest that gastrointestinal function in patients with HS reflects the severity and prognosis of the ailment.