Effects of early estrogen replacement therapy on vascular endothelial senescence and its mechanism in rabbits / 中华老年医学杂志

ABSTRACT

Objective To investigate the effects of early estrogen replacement therapy(ERT) with different doses on aortic endothelial senescence and its possible mechanism. Methods Twenty- eight healthy New Zealand white female rabbits were randomized into four groups group A(n=7), in sham operation;group B(n=7), ovariectomized;group C(n=7), ovariectomized and in low-dose ERT(estradiol benzoate 200 μg,im, QOD) ;and group D(n=7), ovariectomized and in high-dose ERT (estradiol benzoate 1000 μg,im,QOD). All rabbits were fed with high fat diet and the rabbits in group C and group D were given ERT from the 7th day after the operation. Blood samples taken via ear central artery before the operation and after the high fat diet for 4 and 12 weeks were used to determine the concentrations of serum estradiol(E2), total cholesterol(TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), trigtyceride (TG) and asymmetric dimethylarginine(ADMA). After 12 weeks, the aorta was separated for histopathologic analysis and the areas of senescent endothelium and atherosclerotic plaque were calculated.Results (1)After ovariectomized, the concentration of serum estradiol(E2) was significantly lower in group B than in other groups (all P<0.05). Twelve weeks later, the level of E2in was higher group D than in group A and C(both P<0. 05), but there was no significant difference between group C and group A (P< 0. 05). (2)After the high-fat diet for 4 and 12 weeks, there was a notable increase of TC, LDL-C, TG and HDL-C levels in rabbits of each group(all P<0. 01). After 12 weeks, the levels of TC and LDL- C were remarkably higher in group B than in other groups(all P<0. 01), however, the levels of TG and HDL-C were lower in group B than in other groups(all P<0. 01). The concentrations of TC and LDL-C in group C and group D were lower than those in group A (all P<0.01), but the differences of the levels of TG and HDL-C in group C and group D were not significant in comparison with group A (all P>0. 05). There were no significant differences in the lipid levels between group C and D (all P> 0. 05). (3)After 12-week high fat diet, there were a striking increases of serum ADMA level in all four groups (all P>0. 05). The level of ADMA was higher in group B than in other groups (P< 0. 05) andlower in group C and D than that in group A (both P<0. 05). There was no significant difference between group C and D (P<0. 05). (4)12 weeks later, the areas of senescent endothelium and atherosclerotic plaque in group B were significantly larger than those in other groups (all P< 0. 01), and the areas were smaller in group C and D than those in group A (all P<0. 01), there was no significant difference between group C and group D(both P>0.05). (5)Linear correlation analysis showed that there was an obvious positive correlation between the areas of senescent endothelium and atherosclerotic plaque(r=0. 962, P<0. 01), and both of them were positively correlated with the levels of serum AMDA (r=0. 812,0. 824,0. 755,0. 797,0. 749,0. 727), TC (r=0. 812,0. 824) and LDL-C(r=0. 755,0. 797) (all P<0. 01) and negatively correlated with the concentration of serum E2 (r=-0. 762,-0. 743, both P<0. 01).Conclusions Early ERT can improve serum lipid metabolism, reduce ADMA level, inhibit vascular endothelial senescence and attenuate atherogenesis. The delaying effect of estrogen on endothelial senescence may be due to its improving lipid metabolism and lowering ADMA level.