| ObjectiveTo investigate the role of serum heme oxygenase-1 (HO-1) and C reactive protein (CRP) levels in predicting the coronary artery lesion (CAL) in children with Kawasaki disease (KD), and to establish an animal model of coronary artery lesion of KD for further studying the mechanism of HO-1 in CAL caused by KD.MethodsPart I:89 cases with KD were divided into three groups:no coronary artery lesion group (NCAL, n=35), CAL<5mm group (n=44) and CAL≥5mm group (n=10). Acute febrile diseases group (F, n=34) and normal healthy children group (N, n=45) were also set. The levels of malondialdehyde (MDA), HO-1 and superoxide dismutase (SOD) were detected by ELISA before IVIG treatment respectively. CRP and Hb were enrolled to correlation analysis. Some cases were also detected after IVIG treatment.Part II:60 BALB/c mice (6-8 week-old) were randomly assigned to four groups (n=15 each group):control group (intraperitoneal injection with one dose of 0.5 ml PBS), LCWE group (i.p with one dose of 0.5 mg LCWE), TNFa group (i.p with 0.2ug/kg TNFa), LCWE+TNFa group (i.p with 0.5 mg LCWE and 0.2ug/kg TNFa). The coronary arteries and hearts of each group were collected for histological evaluation on days 3,7 and 10 after administration. The levels of serum HO-1 and TNFa were detected by ELISA.ResultsDuring the acute phase of KD, MDA levels were significantly increased. The levels of HO-1 in CAL< 5mm group were significantly higher than the other four groups. The levels of SOD in CAL>5mm group were lower than N group. CRP levels in CAL>5mm group were significantly higher than the other four groups. In 30 KD cases with HO-1≥9ng/ml and CRP> 44mg/L, the incidence of CAL was 56.52%(13/23), which was significantly higher than that of NCAL(0%, 0/7). In 31 CAL cases with HO-1< 9ng/ml and CRP> 85mg/L, the incidence of CAL>5mm was 88.89%(8/9), which was significantly higher than that of CAL< 5mm (36.36%,8/22). HO-1 was negatively correlated with Hb (r=-0.37, P<0.05) in CAL group. After IVIG treatment, H0-1 elevated significantly, MDA decreased in CAL group and SOD activity did not change significantly.In the animal model, neutrophils and lymphocytes were infiltrated in coronary artery in the LCWE group in the first three days. A large number of inflammatory cells, including neutrophils, plasma cells and lymphocytes increased in 7d, while decreased in 10d. Myocardiocytes swelled and were infiltrated with inflammatory cells. Coronary artery widened, but had no significant expansion in LCWE group. In TNFa+LCWE group, inflammatory infiltration and expansion of coronary artery were more obvious than LCWE group, multi-site coronary stenosis and myocardial ischemia were also observed. No such performances were observed in control group. In LCWE group, serum HO-1 concentrations were 0.7±0.52ng/mL and 0.72±0.19ng/mL respectively in 3d and 7d after administration, which was higher than control group, but there were no significant differences between them. The level of HO-1 in TNFa+LCWE group was higher than LCWE group and also had no significant differences between them. The levels of TNFa in LCWE group was 0.47 ± 0.14 ng/ mL and 0.45 ± 0.21 ng/mL respectively in 3d and 7d after administration, which was higher than control group, but there were no significant differences between them.Conclusion1. Oxidative stress and inflammation levels were significantly increased in children with KD. Antioxidant capacity also increased in the early phage. But as inflammation became more serious, antioxidant capacity was inhibited which lead to severer coronary artery disease. Combined analyzing of HO-1 and CRP may predict the occurrence and severity of CAL in the acute phase of KD.2. LCWE can induce coronary inflammation in animal models. When combined with TNFα, severer coronary artery lesion could be induced which would be a reliable and efficient animal model for further study of the mechanism of CAL caused by KD. |
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