The Effects Of Chronic Intrauterine Hypoxia On Atherosclerosis In Adult Rabbit Offspring And Its Possible Mechanism

Objective To investigate the effects of chronic intrauterine hypoxia on atherosclerosis in adult rabbit offspring and discuss its possible mechanism.Methods Sixteen New-Zealand rabbits were divided randomly into 2 groups: chronic intrauterine hypoxia group (CIH, 12%O2, n=8) and Normal oxygen group (NO, 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: Chronic Intrauterine Hypoxia and High Fat Diet (CIH&HFD, n=8), Non-Chronic Intrauterine Hypoxia and High Fat Diet (NCIH&HFD, n=8), Chronic Intrauterine Hypoxia and Normal Diet (CIH&ND, n=8) and Normal Control (NC, n=8).After sixth months, the structure and function of abdominal aorta were examined by ultrasonography and pathology. Then blood-lipid, serum oxidized low-density lipoprotein(ox-LDL) and C-reactive protein(CRP),the protein and mRNA of CRP and monocyte chemoattractant protein-1(MCP-1) in abdominal aorta, and the protein of nuclear factor-κB(NF-κB)) p65 in the cell nuclear of abdominal aorta were examined.Results Chronic intrauterine hypoxia could bring a series of effects on adult rabbit offspring ,such as elevating the level of serum total cholesterol, triglyceride, ox-LDL and CRP, thickening the intimal-medial thickness of abdominal aorta, increaseing the ultrasonography quantitative scoring, upregulating the express of the protein and the mRNA of CRP and MCP-1 in abdominal aorta, enhancing the protein quantity of NF-κB p65 in the cell nuclear of abdominal aorta, and attenuating the endothelial dependent vasodilation(EDV) and strain rate(SR) of abdominal aorta (P<0.05,P<0.01orP<0.001).All these influence caused by CIH could be aggravated significantly when hyperlipemia is imposed(P<0.05 or P<0.001).Conclusions Chronic intrauterine hypoxia is an important factor resulting in atherosclerosis in adult rabbit offspring. The adult rabbit offspring which have ever undergone chronic hypoxia in utero were more sensitive to the impairment of high-fat diet. One of the possible mechanisms involved in the development of atherosclerosis is that chronic intrauterine hypoxia trigger the fetal inflammatory programming which causes serial changes of the express of inflammatory mediators.