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The Expression of Inflammatory Cytokines on the Aorta Endothelia Are Up-regulated in Pinealectomized Rats
Authors:Yu Wang  Xiaoyan Liu  Wei Wang  Wei Song  Lianfeng Chen  Quan Fang  Xiaowei Yan
Affiliation:1. Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
2. College of Basic Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
3. Department of Cardiology, Peking Union Medical College Hospital, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
Abstract:This study was designed to investigate the effect of melatonin on the expression of aortic inflammatory cytokines and its underlying mechanisms in rats. Melatonin deficiency rats (Px, N?=?16) were created by pinealectomy and were fed with normal diet for 16 weeks after the surgery, and compared with sham-operated rats (Con, N?=?14). Serum lipid profile, glucose metabolism parameters, serum oxidative stress and inflammatory biomarkers were evaluated. The expression of inflammatory cytokines in the aorta endothelia was analyzed. To evaluate the signal transduction pathways of melatonin on the expression of cytokines, rat aortic endothelial cell lines (RAECs) were treated with melatonin, and their protein expressions of inflammatory cytokines and phosphorylation levels of relevant signal pathways were detected. At the 16th week after surgery in Px rats, their serum triglyceride, very low density lipoprotein cholesterol, free fatty acid and glucose levels were prominently elevated (all P?P?In vitro, melatonin significantly decreased the expression of MCP-1, VCAM-1 and MMP-9 proteins, along with the suppression of phosphorylation levels of nuclear factor κB (NF-κB)/P65 and p38 mitogen-activated protein kinase (P38-MAPK) in RAECs. Melatonin deficiency elevates the serum inflammatory biomarkers and increases aortic inflammatory responses. Melatonin regulates these inflammatory responses by NF-κB and P38-MAPK involved pathways.
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