Peningkatan ekspresi dan aktiviti enzim 11β-hidroksisteroid dehidrogenase jenis
1 (11β-HSD1) di dalam sel adiposit matang menyebabkan obesiti dan sindrom
metabolik. Fruktos dalam air minuman telah terbukti boleh menyebabkan sindrom
metabolik pada tikus Wistar jantan. Oleh itu, kajian ini dilakukan untuk melihat
kesan ke atas ekspresi dan aktiviti enzim 11β-HSD1 di dalam hati model tikus
sindrom metabolik yang dirangsang dengan air minuman fruktos. Sebanyak 12 ekor
tikus Wistar jantan dibahagikan secara rawak kepada dua kumpulan: kumpulan
kawalan, C (n=6) dan kumpulan yang diberi minuman fruktos 20%, F20 (n=6).
Pemberian makanan dan air minuman selama lapan minggu secara ad libitum. Di
akhir kajian, pengukuran ekspresi enzim 11β-HSD1 di dalam hati dilakukan dengan
menggunakan teknik pewarnaan imunohistokimia. Skor diberikan berdasarkan
intensiti pewarnaan granul di dalam sitoplasma hepatosit menggunakan teknik
‘double-blinded’. Manakala, aktiviti enzim 11β-HSD1 diukur menggunakan teknik
ELISA. Selepas lapan minggu pengambilan air minuman fruktos, kumpulan F20
menunjukkan peningkatan dalam ekspresi dan aktiviti enzim 11β-HSD1 di dalam
hati. Data yang diperolehi menunjukkan bahawa enzim 11β-HSD1 di dalam
hati mungkin memainkan peranan dalam pembentukan sindrom metabolik dan
komplikasinya pada tikus Wistar jantan.
The onset of obstetric antiphospholipid syndrome (APS) occurs when antiphospholipid antibodies act upon the placenta. During pregnancy, APS exhibits traits such as vascular thrombosis, inflammation, and hindered trophoblast implantation. The involvement of microRNA expression has been proposed as a genetic factor contributing to the syndrome's development. MicroRNAs play a role in regulating gene expression in various cellular processes, including the formation of placental tissue. Therefore, additional research is needed to explore the control of placental miRNA in APS. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesised signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation while Retinoblastoma gene (RET), Dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) genes were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.