Effect Of Prenatal Hypoxia On The Expression Of Local Renin - Angiotensin System And NF-kB In Cerebral Cortex From Rat Offspring

Objective: to study the effect of chronic hypoxia during pregnancy on the expression of Local Renin - angiotensin System and NF-kB in cerebral cortex from rat offspring, and to explore prenatal chronic hypoxia-induced possible mechanism of neuronal apoptosis.Methods: 16 pregnant SD rats, of which gestational age is 3 days, were divided randomly into 2 groups:intrauterine chronic hypoxia group (10±1%O2,n=8) and Normal oxygen group (21%O2,n=8). Maternal hypoxic model was established in Sprague Dawley rats from day 6 to 21 of gestation.After delivery,the offspring were raised in the same surrounding. When the descendant rats were 3 and 5 month old,one male offspring and one female offspring of each mother rat were selected .Thus four groups were got as follow: male descendant rats of intrauterine chronic hypoxia group(n=8), female descendant rats of intrauterine chronic hypoxia group(n=8), male descendant rats of non-hypoxia group(n=8), and female descendant rats of non-hypoxia group(n=8). In the offspring ,the expression of ACEmRNA was detected by RT-PCR technique and the expression of the receptors of AngⅡ(AT1R,AT2R) were determined by Western-blot. The structure of cerebral cortex was observed through microscope. The expressions of AT1R,AT2R and NF-kB in Cerebral cortical neurons were detected by immunohistochemistry. Cortical neurons apoptosis was observed by using TUNEL method.Results: The expression of ACEmRNA in cerebral cortex was increased in the offspring of hypoxic exposure group (P<0.05).Compared with the control group,the expression of AT1R in cerebral cortex was worse in the offspring of hypoxic exposure group,while the expression of AT2R was increased.With the offspring growing,the difference between the two groups was increasingly significant .The expressions of NF-kB in Cerebral cortical neurons of intrauterine chronic hypoxia groups were significantly higher than those of control groups (P<0.05),which cerebral cortical neuronal apoptosis rate was also increased more significantly than the normal control group (P <0.05).Conclusion: prenatal hypoxia can stimulate the expression of ACE,AT2R and NF-kB in cerebral cortex of the offspring ,and inhibit the expression of AT1R in the same time,which may be relative with neuronal degeneration or apoptosis in cerebral cortex.