Effects of small interfering RNA targeting TLR4 on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome with hypertension in a rat model

• Published in: Journal of cellular physiology 2018-10, Vol.233 (10), p.6613-6620
• Main Authors: Wu, Jing‐Guo, Xun, Nan, Zeng, Li‐Jin, Li, Zhen‐Yu, Liang, Yan‐Bing, Tang, Hao, Ma, Zhong‐Fu
• Format: Article
• Language: English
• Subjects: Adipocytes; adipocytokine; Adiponectin; Animal models; Apnea; Blood pressure; Cytokines; Enzyme-linked immunosorbent assay; Hypertension; Hypoxia; Inflammation; Interference; Interleukins; Leptin; mRNA; obstructive sleep apnea hyponea syndrome; Physiology; Polymerase chain reaction; Rats; Ribonucleic acid; RNA; RNA interference‐mediated silencing; RNA-mediated interference; Rodents; siRNA; Sleep; Sleep apnea; Sleep disorders; TLR4 protein; Toll-like receptors; toll‐like receptor 4; Transfection; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26364

We explored the effects of RNA interference‐mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real‐time polymerase chain reaction (qRT‐PCR). By enzyme‐linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), and tumor necrosis factor‐α (TNF‐α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference‐mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines. Rats in the TLR siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), and tumor necrosis factor‐α (TNF‐α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference‐mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.