| Objects: To date, only a few studies describing the long-term consequences of cardiac function and myocardial ischemia/reperfusion injury in adult intrauterine chronic hypoxia rabbits offspring. Moreover, the relevant mechanism remains to be elucidated. Given the above considerations, we determine the impact of intrauterine chronic hypoxia on cardiac function and myocardial ischemia/reperfusion injury in adult offspring and further, investigated its potential mechanism in the present study.Methods: 1. Sixteen New-Zealand rabbits were divided randomly into 2 groups: intrauterine chronic hypoxia group (12%O2,n=8) and Normal oxygen group (21%O2,n=8). After delivery, two male offspring of each mother rabbit were selected and breast-fed for three months. Then they were randomly separated into high-fat diet and normal diet respectively. Thus four groups were got as follow: Intrauterine Chronic Hypoxia and High Fat Diet (n=8), Non- Intrauterine Chronic Hypoxia and High Fat Diet (n=8), Intrauterine Chronic Hypoxia and Normal Diet (n=8) and Normal Control (n=8). After six months, cardiac structure and function were examined by ultrasonography and pathology. Then blood-lipid, insulin-like growth factor-1 (IGF-1), apoptotic index and caspase-3 activity in the myocard were measured. 2. The pregnant New-Zealand rabbits were divided into normoxic(n=8) and hypoxic (12% O2 from days 10 to 28 of gestation,n=8) groups. One male offspring of each mother rabbit was selected to study. These male progeny were subjected to heat stress (42℃for 15 min) at 6 months of age. After 24 h, left anterior decending branches were excised and subjected to 30 min of ischemia and 120 minutes of reperfusion.Cardiac structure was observed by light microscope and electron microscope. The expression of heat shock protein 70 (HSP70) in myocard was detected by immunohistochemistry. In addition,myocardial enzyme, apoptotic index and caspase-3 activity in the myocard were examined.Results: 1. Intrauterine chronic hypoxia could bring a series of effects on adult rabbits offspring, such as elevating the level of serum total cholesterol (main effect is 6.82mmol/L), triglyceride (main effect is 0.80mmol/L), thickening the interventricular septum (main effect is 0.66mm), increaseing the Tei index (main effect is 0.08), apoptotic index (main effect is 5.00) and caspase-3 activity (main effect is 0.47unit) in cadiocyte. All these influence caused by intrauterine chronic hypoxia could be aggravated significantly when hyperlipemia is imposed (P<0.05). Intrauterine chronic hypoxia also could descend the ejection fraction of left ventricle (main effect is–4.84%) and downregulate the expression of IGF-1 in myocard. 2. Myocardial enzyme, apoptotic index and caspase-3 activity in the myocard resulting from ischemia-reperfusion was higher by the heat stress pretreatment in intrauterine chronic hypoxia rabbits(4720.31±744.39IU/L; 1849.13±416.58IU/L; 40.43±5.03%; 12.43±1.77unit;respectively)than control rabbits(3388.95±532.43IU/L;1435.13±92.08IU/L;34.40±4.66%;10.58±1.42unit;respectively). In accordance, heat stress significantly increased LV myocardial expression of HSP70 only in normoxic control rabbits.Conclusions: 1. Intrauterine chronic hypoxia may lead to cardiac function dysfunction in adult rabbits offspring. The adult rabbits offspring which have ever undergone chronic hypoxia in utero were more sensitive to the impairment of high-fat diet. 2. Intrauterine chronic hypoxia inhibits myocardial HSP70 synthesis in response to whole body heat stress, leading to a loss of cardioprotection against ischemia-reperfusion injury in the adult heart.
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