The Study Of Heme Oxygenase’s Anti-inflammatory Mechanism And Clinical Significance In Obesity Young Mice And Children

Objective To investigate the change of HO-1 and its relationship with macrophage infiltration and polarization in adipose tissue of obese young SD rats. Forthermore to study the relationship between serum heme oxygenase-1 and anti-inflammatory factor, inflammation factor, physical indexes, blood biochemical changes, carotid artery intima in children with metabolic syndrome(MS).Methods In vivo, three-week old SD rats were randomly divided into 2 groups, routine diet gro up(NC) and high fat diet group(FC). After feed of 4 weeks, triglyceride(TG), high density lipoprotein(HDL-C), fasting glucose and insulin was detected and the insulin resistance index was calculated. The gene expressions of HO-1, IL-6, IL-10 and MCP-1 were determined by quantitative PCR. The expressions of macrophages and M2 macrophages in the visceral adipose tissue were detected by immunohistochemistry method. In the clinical trials, 60 MS children, 60 simple obese children and 60 normal children(control group) were measured height(H), body weight(W), waist circumference(WC), blood routine, fasting blood glucose(FPG) and fasting insulin(FINS). In addition, simple obesity group and metabolic syndrome group were measured serum triglyceride(TG), cholesterol(TC), high density lipoprotein cholesterol(HDL-C), and low density lipoprotein cholesterol(LDL-C). The diameter of the carotid artery and carotid artery intima-media thickness was also measured by the way of Ultrasonic echocardiography. The levels of HO-1, MCP-1, IL-6 and IL-10 were detected by ELISA. The body mass index(BMI), HOMA- IR, and non HDL-C were calculated according to suitable formula.The results were analyzed statistically.Results In animal experients, the levels of FINS, FBG and HOMA-IR in FC were higher than the NC(P < 0.05). The level of HO-1、IL-6、MCP-1 in FC were significantly higher compared with the NC after 4 weeks and the level of IL-10 were lower than NC, difference was statistically significant(P < 0.05). In FC, there was more macrophages expression in adipose tissue, which was detected by DAB staining and MOD analysis. There was no significant difference(P > 0.05) in the expression of F4/80 and CD206 in adipose tissue from FC(P > 0.05). In the clinical trials, the BMI, BP and WC of obese children were much higher than control group significantly. The IR, FINS, TG, non HDL-C, left carotid intima-media thickness and left carotid artery inner diameter of metabolic syndrome group were much higher while the HDL-C was much lower than simple obesity group.The differences were allstatistically significant(P < 0.05).The level of HO-1 in simple obesity group was higher than other groups. The WBC, MCP-1 of metabolic syndrome group were much higher while IL-10 was much lower than simple obesity group. There was no significant difference in the level of IL-6 in groups.There was a significant positive correlation between the HO-1 concentrations and SBP, DBP, IL-10.While a negatively correlated with MCP-1, hs CRP. Multiple liner regression suggested that SBP and TG was an independent risk factor for the serum HO-1 concentration. And carotid intima-media thickness was an independent risk factor for the serum MCP-1 concentration.Conclusion1. The infiltration of macrophage in visceral adipose tissue of obese young SD rats has significantly increased, accompanying with increasing of expression of inflammatory cytokines(such as IL-6, MCP-1).It indicates that obese young SD rats have had low grade inflammation. The expression of anti-inflammatory cytokines like IL-10 decreases, and it is probably because of the consumption of anti-inflammatory cytokines and inflammatory cytokines’ reaction.2. In early stage of young SD rats obesity, HO-1 is reactively increased and probably plays an important role in anti-inflammatory by promoting the inflammatory macrophage type M1 macrophage transform to the anti-inflammatory macrophage type M2 macrophage.This is the protective mechanism of the body against inflammatory reaction in early stage of obesity.3. Obese children have had low grade inflammation. At early stage of obesity, HO-1 is reactively increased and probably plays an important role in anti-inflammatory by promoting the decrease of inflammatory factor and the reduction of anti-inflammatory factor. With the development of metabolic disorder caused by obesity, HO-1 decreases and the inflammatio aggravates4. In obesity children, HO-1 improves inflammatory state by reducing inflammatory factor and increasing anti-inflammatory factor. HO-1 has great significance in improve the inflammation, metabolic disorders and carotid artery intima injury.