Cason Zelma, Benghuzzi Hamed, Tucci Michelle, England Barry
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Biomed Sci Instrum. 2003;39:529-34.
The specific aim of this investigation was to utilize TCPL delivery system as a model for estrogen (E) plus progesterone (P) replacement therapy in post-ovariectomized adult rats mimicking a postmenopausal condition. A total of 20 adult female rats were used in this study. The animals were randomly divided into four different groups: groups II, III and IV were ovariectomized (OVX), OVX plus E (40 mg loaded TCPL), and OVX plus E (TCPL, 40 mg) plus P (TCPL, 80 mg) treatment. Group I animals (n = 5) served as intact control group. Blood samples were collected biweekly for 30 days. Vaginal smears were taken and screened daily during the entire investigation. The total serum levels of E, P, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured by means of radioimmunoassay procedure. Data obtained from this study suggest the followings: (I) OVX resulted in an increase in total serum levels of LH and FSH within 2 days post-ovariectomy, (II) TCPL were capable of releasing sustained levels of E (10-40 pg/ml) and P (2.30-3.75 ng/ml) at the end of second day and continued until the 30th day, (III) the sustained levels of E plus P were able to suppress the post ovariectomy rise of LH and FSH to almost physiological levels, (IV) sustained delivery of E resulted in maturation of vaginal epithelium and the smears exhibited the estrus phase throughout the investigational period, and (V) sustained delivery of E + P induced no estrus and the epithelial changes resembled the OVX group.
本研究的具体目的是利用经皮控释给药系统(TCPL)作为模型,在成年去卵巢大鼠中模拟绝经后状况,进行雌激素(E)加孕激素(P)替代疗法。本研究共使用了20只成年雌性大鼠。动物被随机分为四个不同的组:第二、三、四组进行去卵巢(OVX)手术,然后分别接受OVX加E(40mg负载于TCPL)、OVX加E(TCPL,40mg)加P(TCPL,80mg)的治疗。第一组动物(n = 5)作为完整对照组。每两周采集一次血样,持续30天。在整个研究过程中,每天采集阴道涂片并进行检查。通过放射免疫分析方法测定血清中E、P、促黄体生成素(LH)和促卵泡生成素(FSH)的总水平。本研究获得的数据表明:(I)去卵巢术后2天内,LH和FSH的血清总水平升高;(II)在第二天结束时,TCPL能够持续释放E(10 - 40 pg/ml)和P(2.30 - 3.75 ng/ml),并持续到第30天;(III)E加P的持续水平能够将去卵巢后LH和FSH的升高抑制到几乎生理水平;(IV)E的持续给药导致阴道上皮成熟,在整个研究期间涂片显示为发情期;(V)E + P的持续给药未诱导发情,上皮变化类似于去卵巢组。