Abstract:
Objective To investigate the effects of chronic intrauterine hypoxia on insulin resistance, hypertension, and the correlation between them in adult offspring rats. Methods A total of 25 pregnant Sprague Dawley(SD) rats were randomly divided into 5 groups: 4 prenatal chronic hypoxia groups(H groups) and a control group(C group). Control group was put into anoxic chamber with 21% oxygen concentration. H groups were divided into whole(1-21 day), early(1-7 day), middle(8-14 day) and late(15-21 day) prenatal hypoxia groups(H1, H2, H3, H4 group) with rats being put into hypoxia box(10%±1% O
2) 3 hours per day. Five male and 5 female offspring in each group were studied when the descendant rats were 1 day-, 3 month-and 6-month-old. Fasting blood glucose(FBG) was measured by blood glucose meter, fasting serum insulin(FINS) was detected by radioimmunoassay, and insulin resistance index was calculated by homeostasis model insulin resistance index(HOMA-IR). Renal mass index was also measured. The expression of insulin receptor(InR) protein, the expression of insulin receptor substrate(IRS)-1 and IRS-2 mRNA and the expression of InR, IRS-1 and IRS-2 protein in kidney were detected by immunohistochemistry, fluorescent quantitative polymerase chain reaction(PCR) and Western blot, respectively. Results The blood pressure index of offspring rats in H groups were lower than that in C group at 3 months old, and the difference was more significant at 6 months old(P<0.05). The level of FBG female(5.78±0.21),(5.69±0.29) vs(4.73±0.14) mmol/L, male(5.84±0.19),(5.76±0.24) vs(4.79±0.23)mmol/L, HOMA-IR female(3.35±0.34),(3.23±0.26) vs(2.71±0.23), male(3.55±0.25),(3.18±0.33) vs(2.66±0.39) in the whole pregnancy hypoxia and the early pregnancy hypoxia group were statistically higher than those in C group(P<0.05) at 6 months old. FBG and HOMA-IR were positively correlated with blood pressure(P<0.05). The renal mass index in each hypoxia group was lower than that in C group at 3 months old, and the difference was more significant at 6 months old(P<0.05). The expressions of InR, IRS-1 and IRS-2 mRNA and protein in the kidneys in hypoxia groups were significantly decreased at 6 month old in whole pregnancy and early hypoxia groups when compared with the C group(P<0.05). Conclusions Chronic intrauterine hypoxia may cause insulin resistance and hypertension in adult offspring rats through poor intrauterine growth environment and there is a correlation between insulin resistance and hypertension.