医药学论文：他莫西芬对大鼠子宫内膜增殖和凋亡的影响

【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.

 

【Key words】 endometria; tamoxifen; proliferation; apoptosis

 

他莫西芬（tamoxifen, TAM）是第一代选择性雌激素受体调节剂(SERM),在乳腺癌综合治疗中具有重要地位，是目前临床上应用最广泛、最有效的内分泌治疗药物，也是乳腺癌术后辅助治疗的常用药物，近来还用于预防高危人群乳腺癌的发生。自Killachey［1］等首次报告TAM治疗的乳腺癌病人发生子宫内膜癌以来，陆续有他莫西芬增加子宫内膜癌发病率的报道。1996年IARC(WHO)将他莫西芬列为致癌物。他莫西芬对子宫内膜的影响日益引起人们的关注。本研究以SD大鼠为研究对象，探讨他莫西芬对子宫内膜增殖和凋亡的影响。

 

1 材料与方法

 

1.1 研究对象 雌性SD大鼠（军事医学科学院动物中心提供）40只（体重180-220g），随机分为4组：SHAM组(打开腹腔找到双侧卵巢不切除)，SHAM+TAM组(假手术后给予TAM)，OVX组（行双侧卵巢切除），OVX+TAM组（双侧卵巢切除后给与TAM）；每组10只。