| ObjectiveTo explore the impact of intrauterine chronic hypoxia on insulin resistance,β-cell function and apotosis and islet inflammatory NF-κB expression in the adult male Rat Offspring, as well as to investigate its related elementary mechanisms.MethodsSixteen pregnant SD rats, were divided randomly into the normal control (NC) oxygen group (21%O2, n=8) and the intrauterine chronic hypoxia (ICH) group (10±1%O2, n=8). The SD rats in the ICH group, of which gestational age is from 7 to 21 days, were put in hypoxia box. In the first week, the hypoxia duration was controlled in 4 hours a day; after a week, the hypoxia duration was changed to 2 hours a day. When the descendant rats were 12 weeks old, a male offspring from each mother rat was selected. The fasting blood glucose (FBG) of them was evaluated by Onetouch utra; the fasting insulin (FINS) by radioimmunoassay. Insulin homeostasis model assessment of insulin resistance was measured. The morphology of pancreatic islet was observed by hematoxylin and eosin staining and the area of pancreatic islet were measured by Image pro plus (IPP). The expressions of Insulin, Bcl-2, Bax, NF-κB in islet were detected by means of immunohistochemistry.Results1. The birth weights of the ICH offspring were obviously lighter as compared to those of the NC offspring (4.96±0.39g vs 5.97±0.31g,P<0.05). However, to 4 weeks old, the weights of the ICH offspring generally reached the average levels of the NC offspring (52.5±6.0g vs 53.2±5.6 g). To 12 weeks old, there were no prominent disparity in body weight between both group offspring (378±22.5g vs 382±21.6g,P>0.05). In addition, at birth, the brain weight-to-body weight and heart weight-to-body weight ratio were much higher in the ICH offspring; the pancreas weight-to-body weight and the liver weight-to-body weight ratio were prominently lower in the ICH offspring as compared to the NC offspring.2. The glucose levels of the ICH adult male offspring were higher than those of the NC adult male offspring (5.43±0.29mmol/L vs 4.89±0.22mmol/L,P<0.05). However, there were no significant differences between the ICH adult male offspring and the NC adult male offspring in respect of the insulin levels (12.95±1.29mU/L vs 12.24±1.25mU/L, P>0.05). As compared to the NC adult male offspring, HOMA-IR was higher in the ICH offspring (3.1±0.40 vs 2.6±0.36,P<0.05).3. Majority of pancreatic islet in the ICH adult male offspring presented a hyperplasia and hypertrophy. The area of pancreatic islet in the ICH adult male offspring was larger than those of the NC adult male offspring (256116±6257μ㎡ vs 208653±2794μ㎡,P<0.05).4. The immunohistochemistry detected that the amount ofβ-cell in islet in the ICH adult male offspring was less than those of the NC adult male offspring at low-grade. The expressions of insulin in islet in the ICH adult male offspring were significantly lower than those of the NC adult male offspring (24702±5479 vs 31167±3214,P<0.05); The expressions of Bax in islet of the ICH adult male offspring were significantly higher than those of the NC adult male offspring (36125±7189 vs 18497±5198,P<0.05); The expressions of Bcl-2 in islet was not different between the ICH and the NC adult male offspring (27001±3043 vs 25305±4322,P>0.05). As compared to the NC adult male offspring, Bcl-2/Bax ratios in the ICH adult male offspring was decreased (0.77±0.14 vs 1.45±0.43). The expressions of NF-κB in the ICH adult male offspring were much higher than those of the NC adult male offspring (25546±5846 vs 19483±5107,P<0.05).Conclusion1. Intrauterine chronic hypoxia brought in intrauterine growth retardation and had the ICH offspring pancreatic development impaired; and a phenomena of postnatal catch-up growth appeared in the ICH offspring after birth.2. Intrauterine chronic hypoxia might lead to a dysfunction inβ-cell and insulin resistance in the adult male rats.3. The apotosis of isletβ-cell was enhanced in the ICH adult male offspring.4. For the ICH adult male offspring, there existed an inflammatory environment in pancreatic islet.
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