Significance of intervention with lipoxin A4 in rats with juvenile metabolic syndrome / 中华实用儿科临床杂志

ABSTRACT

Objective To explore the protective role of lipoxin A4 (LXA4) during early process of atherosclerosis formation in rats with juvenile metabolic syndrome (MS).Methods Rat models of juvenile MS were established with 3-week Sprague-Dawley (SD) rats fed on high-carbonhydrates and high-fat diet for 6 weeks.The other qualified ones were randomly grouped into model group,LXA4 low-dose group,LXA4 middle-dose group,and LXA4high dose group,and a control group fed with normal forage.The low,middle,high-dose groups were injected different doses of LXA4 daily,while the model group and control group were injected with the same dose of isotonic NaCl solution for 2 consecutive weeks.After 2-week medication,the visceral adipose tissue were isolated by laparotomy and heart blood collected by thoracotomy under anesthesia,followed the fixation of thoracic and abdominal aortas in the immobilized rats.The mRNA expression level of inflammation cytokines interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),C-reactive protein (CRP) in the adipose tissue were determined by semi-quantitative reverse transcription PCR (RT-PCR),respectively.Secretions of IL-6,and TNF-α in serum were determined by enzyme linked immunosorbent assay (ELISA).Immunocytochemistry was used to label endomembrane and middle-membrane of thoracic aorta,and endothelial cell layer in each group and the ratios of thickness of endomembrane and middle-membrane were compared.Results Compared with the control group,weight,body length and abdominal circumference of juvenile MS rats increased significantly (all P ＜ 0.05),and levels of fasting plasma glucose (FPG),triglyceride (TG),high density lipoprotein cholesterol (HDL-C) and insulin in models increased significantly (P ＜ 0.05).RT-PCR showed that the mRNA expressions of inflammatory cytokines IL-6,TNF-α and CRP in adipose tissue in model rats were upexpressed (all P ＜ 0.05).Compared with model rats,mRNA of IL-6,TNF-oα,and CRP in mid,high-dose rats were downexpressed (all P ＜ 0.05),mRNA of TNF-α in low-dose rat downexpressed (all P ＜ 0.05),and there were no significant differences between mRNA expressions of IL-6,CRP in low-dose and model rats according to statistics (all P ＞0.05).Compared with control group,inflammatory cytokines IL-6,TNF-α secreted in serum of model rats were increased significantly (all P ＜ 0.05),and inflammatory cytokines secreted in serum of intervention rats were decreased significantly compared with model rats (P ＜ 0.05).Pathological changes were as followsHE stainingcompared to model group,aortic tunica intima of model rats were remarkably thickened and endothelial cell layer was fragmented and incomplete,which was attenuated in each intervention group.The ratios of endomembrane and middle-membrane in ratsat the end of consecutive medication for 2 weeks,the ratios of endomembrane and middle-membrane in model rats were significantly greater than those of control group (P ＜ O.05),and the ratios of endomembrane and middle-membrane in high-dose intervention rats were significantly smaller than those of the model group (P ＜ 0.05),but still greater than control group,while there were no statistical differences between the ratios in low,middle-dose intervention rats and model rats (P ＞ 0.05).Conclusions The increasing inflammatory cytokines are involved in early process of atherosclerosis formation in rats with juvenile MS.LXA4 by reducing the expression of inflammatory factor level in adipose tissue,thereby reducing the inflammatory cytokines in serum,alleviate the damage of arterial wall.