Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016. 相似文献
AbstractOxidative stress (OS) has been proposed to play a role in the development of EMs. Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. The Western blotting results showed that the relative expression of PRDX4 was significantly increased in ectopic endometria compared with the normal endometria of EMs-free (p?<?.05). The H2O2 concentration was also significantly higher in the ectopic endometrium. PRDX4 siRNA was transfected into primary ectopic endometrial stromal cells (EESCs). The viability of the transfected EESCs was measured by CCK-8 assay, and the results showed significantly decreased cell viability. Furthermore, the apoptosis rate and ROS generation in flow cytometry assays were significantly increased after the knockdown of PRDX4 expression (p?<?.05). Scratch assays and transwell assays revealed that decreased expression of PRDX4 mediated by siRNA inhibited EESC migration and invasion. In conclusion, these findings indicate the potential role of PRDX4 in the development of EMs and PRDX4 as a possible therapeutic target for EMs treatment. 相似文献
Background: Previous genome-wide association study (GWAS) has revealed the association between MYP10 at 8p23 and MYP15 at 10q21.1 and high myopia (HM) in a French population. This study is managed to discover the connection between some single nucleotide polymorphism (located at MYP10 and MYP15) and Han Chinese HM.
Methods and Results: This case-control association study contained 1673 samples, including 869 ophthalmic patients and 804 controls. Twelve tag SNPs have been selected from the MYP10 and MYP15 loci and genotyped by SNaPshot method. Among 12 SNPs, rs4840437 and rs6989782 in TNKS gene were found significant association with HM. Carriers of rs4840437G allele and rs4840437GG genotype created a low risk of high myopia (P = .036, OR = 0.81, 95%CI = 0.71–0.93; P = .016, OR = 0.73, 95%CI = 0.56–0.96; respectively). Carriers of rs6989782T allele and rs6989782TT+CT genotype also had a decreased risk of high myopia (P = .048, OR = 0.82, 95%CI = 0.71–0.94; P = .006, OR = 0.74, 95%CI = 0.59–0.92; respectively). Other 10 SNPs displaced nonsignificant association with HM. Additionally, the risk haplotype AC and the protective haplotype GT, generated by two SNPs in TNKS, were considerably more likely to be association with HM (for AC, P = .002 and OR = 1.26; for GT, P = .027 and OR = 0.84).
Conclusions: Our results demonstrated that some heritable variants in the TNKS gene are associated with HM in the Han population. The possible functions of TNKS in the development and pathogenesis of hereditary high myopia still require further researches to identify. 相似文献