ABSTRACT
Objective: To discuss the effect of Gandou decoction (GDD) on the immune index of spleen in TX mice of Wilson's disease model. Method: The mice were divided into normal group, model group and GDD or tetrathiomolybdate(TM)treatment group, with 20 mice in each group. Each group was fed in various ways for 30 successive days. Normal group:10 normal DL mice were randomly selected and feed normally. Model group:20 TX mice were randomly selected and feed with 2 mL·kg-1·d-1ig saline by gavage twice per day. GDD or TM treatment group:80 TX mice were randomly selected and feed with 2 mL·kg-1·d-1 ig Gandou decoction 22,44,66 g·kg-1 or tetrathiomolybdate by gavage twice per day. ICP-MS was used to compare the expressions of trace elements inside the mice's spleens, flow cytometry was applied to detect the mice T lymphocyte subsets of splenic tissue CD4+, CD8+, CD4+/CD8+, and Western blot was used to detect the expressions of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-8 (IL-8), interleukin-17 (IL-17) and interleukin-18 (IL-18). Result: Flow ICP-MS results showed that GDD can reduce Cu of mice's spleen, flow cytometry results showed that CD4+and CD8+in model group were increased than those in normal group (P+/CD8+was decreased (P+and CD8+in middle and high-dose GDD groups were decreased (P+/CD8+was increased. According to Western blot detection, compared with normal group, the expressions of IL-2, IL-8, IL-17, IL-18, TNF-α and IFN-γ in the model group were increased (Pα, IFN-γ, IL-2, IL-8, IL-17 and IL-18 in the GDD middle and high or TM group were decreased (PPα in the GDD low were decreased (PConclusion: Spleen of TX mice shows the cellular immunity hyperfunction, which is mainly dominated by the negative immunoloregulation. GDD has a certain effect in regulating cellular immunity hyperfunctional state of TX mice, but it's difficult to thoroughly change the negative immune regulation.
ABSTRACT
<p><b>OBJECTIVE</b>This study aimed to investigate the susceptibility of mice with streptozotocin(STZ)-induced diabetes mellitus (TIDM) to the uptake of pentavalent inorganic arsenic (iAsV) and the possible molecular mechanism.</p><p><b>METHODS</b>TIDM was induced in mice by STZ. TIDM and normal mice were treated with 15.0 mg/kg Na2HAsO4·12H2O by intragastric administration. Then, the concentrations of arsenic in various tissues were measured by atomic fluorescence spectrometry. The gene expression levels of Pit1 and Pit2 were quantified by real-time RT-PCR, and their protein levels were detected by Western blotting in mouse heart, kidney, and liver tissues.</p><p><b>RESULTS</b>The concentrations of arsenic in STZ-induced TIDM mouse tissues were higher at 2 h after intragastric administration of Na2HAsO4·12H2O. Compared with the levels in normal mice, PIT1 and PIT2, which play a role in the uptake of iAsV, were upregulated in the livers and hearts of TIDM mice. PIT1 but not PIT2 was higher in TIDM mouse kidneys. The upregulation of Pit1 and Pit2 expression could be reversed by insulin treatment.</p><p><b>CONCLUSION</b>The increased uptake of iAsV in TIDM mouse tissues may be associated with increased PIT1 and/or PIT2 expression.</p>
Subject(s)
Animals , Male , Mice , Arsenic , Pharmacokinetics , Diabetes Mellitus, Experimental , Metabolism , Environmental Pollutants , Pharmacokinetics , Gene Expression Regulation , Physiology , Mice, Inbred ICR , Sodium-Phosphate Cotransporter Proteins, Type III , Genetics , Metabolism , Transcription Factor Pit-1 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore susceptibility genes associated with yang-deficiency constitution using single nucleotide polymorphism (SNP) genotyping.</p><p><b>METHODS</b>Based on an epidemiological survey, 30 volunteers with yang-deficiency constitution and 30 volunteers with a balanced constitution were included according to the Classification and Determination Standards of Constitutions in Traditional Chinese Medicine. Peripheral blood was collected and DNA was extracted from white blood cells. A genome-wide association study (GWAS) was conducted by SNP 6.0 genotyping at the Beijing CapitalBio Corporation Ltd. A minimum association P-value (Fisher's exact value) of less than 10(-4) in the allele, genotype, dominant, and recessive models served as the standard for significant association of SNP with yang-deficiency constitution.</p><p><b>RESULTS</b>Among the four genetic models, a total of 42 SNPs were significantly associated with yang-deficiency constitution (Fisher's exact P-values P<10(-4)). These SNPs were adjacent to more than 20 genes, including RGS6, mGluR5, GAPDHL19, and IKZF1.</p><p><b>CONCLUSION</b>Yang-deficiency constitution exhibits the characteristics of polygenic inheritance. This pilot study suggests that the polymorphisms in RGS6, mGluR5, GAPDHL19, and IKZF1 are associated with changes in cyclic adenosine monophosphate and cyclic guanosine monophosphate levels, memory, metabolic energy status, and immune function, respectively in people with yang-deficiency constitution.</p>