ABSTRACT
Objective To investigate the single nucleotide polymorphisms(SNPs) of 5-HT1BR(rs6298),5-HT2AR(rs6311,rs6313) and 5-HT2BR(rs765458) gene,and their gene-gene interactions on suicidal behavior in major depressive disorder.Methods The blood samples were taken from 281 depression patients with impulsive suicide attempt and 281 age-matched healthy controls from a hospital in Harbin city,Heilongjiang province.The DNA isolated from blood samples and was genotyped using TapMan SNP genotyping probe.χ2 test was used to compare differences in the distribution of gene alleles between cases and controls.Haplotype and linkage disequilibrium(LD) analysis was performed using Haploview 4.0 software.GMDR was used to analyze the gene-gene interaction.Results The rs6313 and rs6311 of the 5-HT2AR gene were in strong linkage disequilibrium (D=0.756,r2=0.375).There was a significant gene-gene interaction of 5-HT1BR (rs6298),5-HT2AR (rs6311,rs6313) and 5-HT2BR(rs765458) on suicidal behavior(P<0.05).In this model,the test accuracy was 0.6182 and CV value was 10/10.Conclusion A haplotype containing rs6311 and rs6313 of 5-HT2AR gene is associated with suicidal behavior.The interaction of 5-HT1BR gene (rs6298),5-HT2AR gene (rs6311,rs6313) and 5-HT2BR gene (rs765458) are associated with depression suicidal behavior.
ABSTRACT
Objective To investigate the effect of fluoride on osteoclast in bone tissue of rats and its mechanism.Methods Twenty specific pathogen free male Wistar rats aged 3 weeks were randomly divided into two groups by weight (each group has 10).The rats of control group drink distilled water and treatment group drink distilled water containing 100 mg/L fluoride.The rats were fed for 3 month.The dental fluorosis in rats was observed.The ion selective electrode method was used to measure bone fluoride accumulation.The pathological changes of bone tissue in rats were observed under light microscope.The osteoclast was identified by tartrateresistant acid phosphatase (TRAP) staining.The calcineurin (CaN) activity of serum was measured by detection of free phosphate with malachite green.The bicinchoninic acid (BCA) method was used to detect total protein concentration of serum.The colorimetry method was used to detect calcium and malondialdehyde (MDA) levels in serum.The enzyme linked immunosorbent assay (ELISA) method was used to detect calmodulin (CaM) content.Results By the end of the experiment,none dental fluorosis was detected in control group,all rats in fluoride group had dental fluorosis.The bone fluoride content of rats in fluoride group [(4 460.671 ± 418.548) mg/kg] was about 7.6 times higher than that in control group [(582.534 ± 58.342) mg/kg,t =-29.020,P ＜ 0.01].Compared with the control group,the bone tissue of rats in fluoride group showed thicker bone trabecular,sclerotin fusion and incomplete mineralization.Positive signal intensity of TRAP staining of bone tissue in fluoride group was significantly higher than that in control group.The number of osteoclast formation in fluoride group [10 (5-12)] was significantly higher than that in control group [3 (2-4);U =92.5,P ＜ 0.01].CaN activity in serum of rats in fluoride group [(3.334 ± 0.654) nmol/mg prot] was significantly higher than that in control group [(1.289 ± 0.361) nmol/mg prot;t =-6.346,P ＜ 0.01].The Ca and CaM content of serum in rats were not significantly different between the two groups.However MDA content in fluoride group [(7.703 ± 2.954) μmol/L] was significantly higher than that in control group [(3.958 ± 1.965) μmol/L,t =-2.968,P ＜ 0.05].Conclusion Excessive fluoride may increase osteoclast formation in bone tissue of rats,and the mechanism might be fluoride stimulated CaN activity through oxidative stress pathway.
ABSTRACT
Objective To observe the effects of sodium arsenite (NaAsO2) on apoptosis in primary cultured rat cerebellar granule cell and nerve globin mRNA expression.Methods Twenty 7-8 days postnatal Wistar rats were selected and decapitated cerebellar cortex, granular cell suspension was prepared and 4 × 109/m2 cells were seeded in the culture flask.Cells were exposed to different concentrations NaAsO2 [0 (control), 2, 5 and 10 μmol/L] for 24 h and intracellular reactive oxygen species (ROS) content and apoptosis were determined by laser confocal,while real-time quantitative PCR was used to detect mRNA expression in cultured cells after 24 and 48 h cell culture.Results Fluorescence intensity of ROS of 0, 2, 5, 10 μmol/L fluoride groups were 421.32 ± 53.52,1 082.09 ± 321.58, 2 223.02 ± 1 011.37 and 1 366.87 ± 102.14, the difference was statistically significant (F =5.873,P ＜ 0.05);Apoptosis rates were (8.91 ± 5.63)％, (26.46 ± 1.77)％, (43.65 ± 14.45)％ and (56.04 ± 6.95)％, the difference was statistically significant (F =18.369, P ＜ 0.05);24 h nerve globin mRNA expression were 1.00 ± 0.06,0.77 ± 0.22, 0.43 ± 0.18 and 0.42 ± 0.14, the difference was statistically significant (F =18.235, P ＜ 0.05);48 h nerve globin mRNA expression were 1.00 ± 0.01, 0.89 ± 0.09, 0.60 ± 0.16 and 0.08 ± 0.02, the difference was statistically significant (F =80.843, P ＜ 0.05).Conclusion With increased NaAsO2 concentration, ROS and apoptosis levels are increased, while nerve globin mRNA expression is significantly reduced, suggesting that after the body is stimulated, protective proteins might be consumed, further suggesting nerve globin expression might be involved in nerve damage caused by arsenic.