RESUMEN
BACKGROUND A growing body of evidence suggests that systemic lupus erythematosus (SLE) may result in reversible cognitive dysfunction. Vitamin D is considered important for neurons. The therapeutic effect of vitamin D was evaluated in a rat model of SLE. MATERIAL AND METHODS There were 20 male MRL/lpr mice randomly divided into the SLE model group and the vitamin D group, in addition, 10 male C57BL 6J mice were used as the control (CON) group. Vitamin D was administered intraperitoneally (2 µg/kg) for 4 weeks. After 4 weeks of continuing intervention, we tested the cognitive function using the Morris water maze. The expression of vitamin D receptor (VDR), amyloid-ß, caspase-3, and Bcl-2 were detected by western blot analysis. RESULTS In the present study, we observed that vitamin D treatment alleviated neurobehavioral deficits in the mice with SLE. At the molecular levels, administration of vitamin D activated the expression of VDR and reduced the number of dead cells in the CA1 region of the hippocampus as well as regulated caspase-3 and Bcl-2 expression. CONCLUSIONS In conclusion, our results indicated that vitamin D played a protective role by suppressing inflammatory cytokines, thereby ultimately inhibiting the progression of apoptosis in a mouse model of SLE. Vitamin D may be promising as a protective intervention in SLE with cognitive dysfunction, and more and more experiments are warranted for its clinical testing in the near future.
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Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Vitamina D/uso terapéutico , Péptidos beta-Amiloides/metabolismo , Animales , Caspasa 3/metabolismo , Citocinas/metabolismo , Hipocampo/patología , Mediadores de Inflamación/metabolismo , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factores de Tiempo , Vitamina D/farmacologíaRESUMEN
This study investigates cross-talk of the related bioactivity mediators in silica-induced pulmonary inflammatory and fibrosis on rats, which contributes to the preventive and therapeutic effect of soluble TNF-α receptor. Wistar rats received saline or 50 mg of quartz by intratracheal instillation. Rats in drug-treated groups were given soluble tumor necrosis factor-α (TNF-α) receptor (500 µg) by hypodermic injection on days 1, 5 and 8 after operation. At 7 days or 14 days after instillation, rats were killed to observe the degree of injury and expression of the related bioactivity mediators including nuclear factor KB (NF-KB), nitric oxide, interleukin-1ß, interleukin-10, transforming growth factor beta 1 (TGF-ß1), TNF-α, interferon-Y (IFN-Y) and granulocyte macrophage colony-stimulating factor (GM-CSF). The area percentages of type I and III collagens in intervention group were lower than those in silica group. The expression of NF-κB, TGF-ß1, and COL I were lower in intervention group than in silica group(p < 0.05) and GM-CSF was significantly higher (p < 0.05) at 7 days after instillation, however, NF-κB, TGF-ß1, and COL I were identically lower in intervention group than in silica group, and TNF-α, IFN-γ, and GM-CSF were higher at 14 days after instillation. It may be concluded that soluble TNF-α receptor upregulating or downregulating the expression of the related bioactivity mediators results in decreasing lung injury induced by silica.
Asunto(s)
Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Dióxido de Silicio/toxicidad , Silicosis/tratamiento farmacológico , Animales , Colágeno/sangre , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-1beta/sangre , Masculino , FN-kappa B/sangre , Óxido Nítrico/sangre , Ratas , Ratas Wistar , Transducción de Señal , Factor de Crecimiento Transformador beta1/sangreRESUMEN
Systemic lupus erythematosus (SLE) complicated with Pneumocystis jiroveci pneumonia (PCP) is a clinical complex with unsatisfying treatment efficacy and poor prognosis which is difficult to be diagnosed at early stage. The present study aimed to investigate the clinical features of SLE with PCP, recognize the early onset indicating factors, and evaluate the treatment efficacy of combined caspofungin and trimethoprim/sulfamethoxazole (coSMZ).We reviewed data of 9 patients admitted with SLE-PCP and treated with caspofungin combined with coSMZ at Tangshan Gongren Hospital from January 2013 to December 2017. Patients' clinical manifestation and laboratory data [leucocyte, lymphocyte, cluster of differentiation 4 (CD4)T cell, lactate dehydrogenase (LDH), blood gas, etc] were compared before and after treatments. And the early onset factors of SLE-PCP, treatment efficacy of combined caspofungin and CoSMZ were analyzed.Among these 9 patients, 8 patients suffered renal impairment, and all of them had been taking prednisone in the past 3 months at an average dose of 29.4â±â13.6âmg/day. In addition, they had taken at least one kind of immunosuppressants. Laboratory data (leucocyte, lymphocyte, CD4T cell, PaO2, LDH) were remarkably abnormal at hospital admission, but they were improved significantly after 2 weeks of treatment, which is also statistically significant (Pâ<â.05), except that leukocyte had no significance change to the value at admission (Pâ=â.973). In addition, none of the studied patients died.The results of the study indicated that long-term use of glucocorticoids and immunosuppressants, low CD4T cell count, and renal impairment are the early-onset factors for SLE-PCP, caspofungin, when combined with CoSMZ, it could be a promising and effective strategy to treat SLE with PCP.