RESUMEN
<p><b>OBJECTIVE</b>To study the actions of transcription factors, T-bet and GATA-3, and their relevant signal transduction pathways on the immune-related pathogenesis with chronic aplastic anemia (CAA), and to investigate the immunological regulation mechanism of Shengxue Mixture (SXM) in regulating levels of Th cell imbalance, transcriptional factor and relevant signal pathways.</p><p><b>METHODS</b>All CAA patients selected from Yueyang Hospital of Shanghai University of traditional Chinese medicine were equally randomized into the treated group and the control group, 20 patients in each group, and 20 healthy persons were selected as normal group, the former was treated with SXM according to patients' syndrome patterns, namely, SXM-1 was given to patients of Pi-Shen yang-deficiency pattern, and SXM-2 to those of Pi-Shen yin-deficiency pattern. Patients in the control group were treated with cyclosporin A (CsA). The mRNA expressions of T-bet, GATA-3, signal transducers and activators of transcription 4 (STAT4) and 6 (STAT6) in peripheral blood mononuclear cell (PBMNC) of patients were determined using real-time fluorescent quantitation polymerase chain reaction before and after treatment, meantime, the Th1/Th2 proportion in peripheral blood, and levels of IFN-gamma, IL-12 and IL-4 in PBMNC-cultured supernatant were detected by flow cytometry and enzyme linked immunosorbent assay.</p><p><b>RESULTS</b>The mRNA expressions of PBMNC T-bet and STAT4, ratios of T-bet/GATA-3, Th1 proportion and Th1/Th2 ratio, levels of IFN-gamma and IL-12 in PBMNC-cultured supernatant were all significantly higher in CAA patients than in healthy controls (P < 0.01), which were lowered after treatment but didn't reach the normal range (all P < 0.01), excepting for IL-12 level. Comparisons of the changes between the two treated groups showed insignificant difference (P > 0.05). While the difference between patients and healthy persons in terms of GATA-3, STAT6, Th2 proportion, and IL-4 were insignificant (P > 0.05), either before or after treatment.</p><p><b>CONCLUSIONS</b>Abnormal activation of IFN-gamma/T-bet and IL-12/ STAT4 pathways, as well as Th1/Th2 balance deviating to Th1 excursion play vital roles in the immunological pathogenesis of CAA. SXM and CsA could lower the aforesaid abnormal activation and correct Th1 hyper-polarization, so as to alleviate the over-activated cell-mediated immunity to eliminate hematopoietic depression in CAA patients.</p>
Asunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anemia Aplásica , Quimioterapia , Alergia e Inmunología , Metabolismo , Enfermedad Crónica , Citocinas , Metabolismo , Diagnóstico Diferencial , Medicamentos Herbarios Chinos , Usos Terapéuticos , Factor de Transcripción GATA3 , Genética , Metabolismo , Medicina Tradicional China , Fitoterapia , ARN Mensajero , Genética , Metabolismo , Transducción de Señal , Proteínas de Dominio T Box , Genética , Metabolismo , Balance Th1 - Th2RESUMEN
The study was aimed to explore the effects of T-bet (T-box expressed in T cell), GATA-3(GATA binding protein 3) and relevant signal transduction pathways on the immune-related pathogenesis of chronic aplastic anemia (CAA), and to investigate the immunological regulation mechanism in the treatment of CAA by using cyclosporine A (CsA) at the level of Th cell imbalance, transcriptional factors, and relevant signal pathways. The real-time fluorescent quantitative polymerase chain reaction (real-time FQ-PCR) was used to determine the mRNA expression of T-bet, GATA-3, signal transducers and activators of transcription 4 (STAT4) and signal transducers and activators of transcription 6 (STAT6) in peripheral blood mononuclear cell (PBMNC) of CAA patients before and after treatment with CsA; the flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA) were used to determine the Th1/Th2 proportion in peripheral blood, and levels of IFN-γ, IL-12 and IL-4 in PBMNC-cultured supernatant. Healthy people were included to test the above indexes. The results showed that the mRNA expression of PBMNC T-bet, STAT4, T-bet/GATA-3 ratio, Th1 proportion, Th1/Th2 ratio and levels of IFN-γ and IL-12 in PBMNC-cultured supernatant of CAA patients were significantly higher than those of healthy people (p < 0.01). After treating with CsA for 6 months of CsA treatment, expression of T-bet, STAT4, T-bet/GATA-3 ratio, Th1 proportion, IFN-γ and IL-12 levels were lower than before, however, the expression of T-bet, STAT4, T-bet/GATA-3 ratio, Th1 proportion and IFN-γ had not been reduced to normal state. Compared to healthy people, no significant difference existed in the mRNA expression of GATA-3, STAT6, Th2 proportion, as well as level of IL-4 before and after treatment (p>0.05). It is concluded that the abnormal activation of IFN-γ/T-bet and IL-12/STAT4 pathways, as well as Th balance deviating to Th1 excursion play vital roles in the immunological pathogenesis of AA. CsA lowers the abnormal activation of IFN-γ/T-bet and IL-12/STAT4 pathways to correct Th1 hyperpolarization, which may reduce the abnormally activated cell-mediated immunity and relax hematopoietic depression of AA patients.
Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anemia Aplásica , Quimioterapia , Alergia e Inmunología , Metabolismo , Estudios de Casos y Controles , Ciclosporina , Farmacología , Factor de Transcripción GATA3 , Metabolismo , Interferón gamma , Metabolismo , Interleucina-12 , Metabolismo , Interleucina-4 , Metabolismo , Factor de Transcripción STAT4 , Metabolismo , Factor de Transcripción STAT6 , Metabolismo , Transducción de Señal , Proteínas de Dominio T Box , Metabolismo , Células TH1 , Células Th2RESUMEN
With the fast development of medicinal animals as new drugs, research on Periplaneta americana become hot recently. Several drugs which mainly consisted of P. americana were approved for clinical applications. The chemical constituents and pharmacological bioactivities of this insect were summarized herein, which provides informativon for further researches on this medicinal animal.
Asunto(s)
Animales , Aminoácidos , Farmacología , Antibacterianos , Farmacología , Antineoplásicos , Farmacología , Cardiotónicos , Farmacología , Cicloparafinas , Farmacología , Materia Medica , Farmacología , Estructura Molecular , Neuropéptidos , Farmacología , Periplaneta , QuímicaRESUMEN
<p><b>OBJECTIVE</b>To observe the clinical effect of Shengxueling (SXL) on idiopathic thrombocytopenic purpura (ITP), and study the possible mechanism.</p><p><b>METHODS</b>Eighty-six cases of ITP were randomly divided into two groups. The SXL group, 56 patients treated with SXL, a traditinal Chinese medicine and 30 patients administered with prednisone were taken as control. Each group took drugs for 3 months and was under follow-up observation.</p><p><b>RESULTS</b>In the SXL group, the total effective rate was 85.71%, similar to prednisone 83.33% (P > 0.05) for 3 months, but the total effective rate of SXL (91.07%) were obviously better than that of the control group (53.33%) (P < 0.01) for 6 months and had no obvious adverse reaction. The patients bleeding was alleviated or stopped, the general condition was improved. At the same time, blood platelet count (PLT) was increased, platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly dropped, the level of natural killers cells activity (NKa) increased, the rate of T lymphocyte subsets gradually returned to normal level. Megakaryocyte tended to maturation on bone marrow smear after treatment. All differences above were statistically significant.</p><p><b>CONCLUSION</b>SXL is an effective and safe medicine for ITP. Its mechanism could regulate cytoimmune, inhibit platelet antibody to reduce the destruction of platelet, increase the number of platelet, promote the division and maturation of megakaryocyte, facilitate the production and release of platelet, lower the fragility of capillary, prevent and cure hemorrhagic tendency.</p>