他莫西芬对大鼠子宫内膜增殖和凋亡的影响 (pdf)

    【摘要】 目的 通过他莫西芬(tamoxifen, TAM)对大鼠子宫内膜增殖细胞核抗原(PCNA)和凋亡的影响，探讨他莫西芬导致子宫内膜病变的可能机制。方法 40只成年雌性SD大鼠随机分为四组：假手术组(SHAM组)、假手术+TAM组(SHAM+TAM组)、去势手术组(OVX组)、去势手术+TAM组(OVX+TAM组)，每组10只，用药28天后，处死大鼠取子宫进行形态学检查，PCNA抗原免疫组化分析及TUNEL凋亡检测。结果 他莫西芬可以使去势大鼠子宫湿重增加，上皮增厚，基质增加，可以降低未去势大鼠子宫湿重；SHAM+TAM组PCNA阳性细胞数少于SHAM组。TUNEL凋亡检测阳性细胞给药组明显少于未给药组(P<0.05)。结论 雌激素水平会影响他莫西芬对子宫内膜的作用，他莫西芬导致子宫内膜病变的基础可能并不是促进细胞的增殖而是通过其他途径抑制细胞凋亡引起的。

    【关键词】 子宫内膜；他莫西芬；增殖；凋亡

    Effects of tamoxifen on endometrium proliferation and apoptosis of rat

    ZHANG Mei，YUAN Ben-li. Institute of Pharmacology and Toxicology, Academy of Military Medical SciencesG, Beijing 100850,China

    【Abstract】 Objective To investigate the possible role of PCNA and apoptosis involved in tamoxifen-induced endometrium pathogenesis. Methods Forty female SD rats were randomly assigned into four groups: sham operated group (SHAM), sham operated plus tamoxifen (SHAM+TAM), bilaterally ovariectomized group (OVX) and ovariectom plus tamoxifen group (OVX+TAM). All animals were treated with tamoxifen or solvent control for 28 days. Then animals were sacrificed and uteri were removed for histological examination, immunohistochemical detection for PCNA and apoptosis cells. Results After tamoxifen administration, the uterus weight of ovariectomized rat was increased , while utertus weight of SHAM rat was decreased . The positive signals of PCNA are fewer in SHAM group than that in SHAM+TAM. Compared with control group, apoptosis cell number significantly decreased after treated with tamoxifen.Conclusion Estrogen level could influence the effect of tomaxifen on endometrium. Inhibition of apoptosis but not induction of endometrium proliferation is probably involved in the effect of tamoxifen on endometrium. ......