Effects of different doses of estradiol on apoptosis of T lymphocytes in ovariectomized mice and their possible mechanisms / 中华老年医学杂志

ABSTRACT

Objective To investigate the effects of different doses of estradiol on apoptosis of T lymphocytes from spleens in ovariectomized mice and explore the possible mechanisms.Methods The mice splenic T lymphocytes were isolated and divided into ten groups young group, sham- ovariectomized group, ovariectomized group, ovariectomized plus estradiol(10-11, 10-10, 10-8 and 106groups, ovariectomized plus estradiol (10-10mol/L) plus 1CI182 780 (10-7tool/L) group, ovariectomized plus estradiol(10-10mol/L) plus 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPP, 10-6mol/L) group, ovariectomized plus estradiol(10-10mol/L) plus pyrroline dithiocarbamate(PDTC, 10-6mol/L) group. The apoptosis rates were determined by flow eytometry using Annexin V-FITC/ PI and the protein levels of ERa, ERβ, Bax, Bcl-2 and P65 were detected by Western blot. Results The apoptosis rate of ovariectomized group was(19. 4±2.5)%, which was higher than that of young group [(14.6±2.4%) 3 and sham-ovariectomized group [p (14.5±2.3)%], and the levels of Bcl-2 and nuclear P65 were lower than the young group [(0. 25±0. 05, 0. 09±0. 01) vs. (0. 40± 0.07,0. 15±0. 02), P<0.01]. The ovariectomized plus estradiol (10-10tool/L) group had lower apoptosis rate and higher Bcl-2 and P65 levels compared to the ovariectornized group[(16.6±1.8)% vs.(19.4±2.5)%,P<0.05;0.36±0.03 vs. 0.25～0.05, 0.14±0.01 vs. 0.09±0.01, P< 0. 01)], while the ovariectomized plus estradiol(10-8mol/L, 10-6tool/L) groups had higher apoptosis rates than the ovariectomized group[(22. 55±2. 5)% vs. (19. 4±2. 5)% ,P<0. 05;(27.8±3.1)% vs. (19.4 4±2. 5)%,P<0. 01, respectively]. The 2protein levels of ERa and ERβ of ovariectomized group were 0. 23±k0.01 and 0. 22±0. 03, respectively, which were lower than those of young((0. 27±0. 02) and (0. 29±0.04)] and sham-ovariectomized group [(0. 28±0. 03) and (0. 29±0.02)]. The ovariectomized plus estradiol(10-1110-1010-8tool/L) groups had higher while ovariectomized plus estradiol(10-6mol/L) group had lower ERα and ERβ protein levels (0. 09±0. 01,0. 14±0.02) than the ovariectomized group(P<0. 01). There was no significant difference between ovariectomized plus estradiol(10-10mol/L) plus ICI182 780 group or ovariectomized plus estradiol(10-10tool/L) plus PDTC group and ovariectomized group [(19.4±1.6)% vs. (19.4±2. 5)%, (21.0±2. 9)% vs. (19.4d±2. 5)%, P>0. 05). There were also no significant difference between ovariectomized plus estradiol(10-10mol/L) plus MPP group and ovariectomized plus estradiol (10-10mol/L) grou p[(16.9±2.2)% vs. (16.6±1.8)%, P>0.05]. Conclusions The ovariectomy of mice leads to increased apoptosis rates of splenic T lymphocytes. The effects of estradiol on the apoptosis of T lymphocytes in ovariectomized mice are dependent on doses physiological dose of estradiol inhibits while higher dose of estradiol exacerbats the apoptosis of T lymphocytes in ovariectomized mice.Physiological dose of estradiol may act on Rice T lymphocytes via ERβ and NFkB signaling.