Cason Z, Benghuzzi H, Tucci M, Scott A, England B
University of Mississippi Medical Center, Jackson 39216, USA.
Biomed Sci Instrum. 2000;36:221-6.
Previous studies conducted in our laboratories have documented that tricalcium phosphate lysine (TCPL) delivery system can be utilized to deliver estrogen (E) and combination of estrogen with progesterone (E + P) at sustained levels for long duration in intact rats. The specific aim of this investigation was to attempt to reverse the endometrial changes resulted from post-ovariectomy by exogenously delivering sustained levels of E and E + P. A total of 27 adult female rats were used in this study. The animals were randomly divided into seven different groups: groups 1 animals served as intact control group, groups 2 and 6 animals were ovariectomized, 3 and 7 were ovariectomized (OVX) and implanted with TCPL loaded with E (20 mg loaded TCPL), and group 4 was OVX and implanted with E (TCPL, 20 mg) + P (TCPL, 40 mg.) treatment. Group 5 animals served, as intact control group. Blood samples were collected biweekly for 47 days. Vaginal smears were taken and screened daily during the entire investigation. Histopathological evaluations were conducted on reproductive as well as vital organs (H & E). Data obtained from this investigation suggest the following: (I) OVX resulted in an increase in total body weight, however E and E + P maintained the body weights at prior ovariectomy level, (II) sustained delivery of E resulted in maturation of vaginal epithelium and the smears exhibited the estrus at the end of 72 hours post implantation and continued this trend for the duration of the study, (III) E + P treatment induced no estrus and the epithelial changes resembled the OVX group, and (IV) E and E + P treatment resulted in a significant different (P < 0.05) in MDA levels compared to OVX and intact control groups. Results of this investigation conclude that sustained delivery of E and E + P by TCPL can be utilized to maintain the normal function of the reproductive organs and could serve as an efficient and safe therapy in estrogen deficient patients.
我们实验室之前进行的研究已证明，磷酸三钙赖氨酸（TCPL）给药系统可用于在完整大鼠体内长时间持续递送雌激素（E）以及雌激素与孕酮的组合（E + P）。本研究的具体目的是尝试通过外源性递送持续水平的E和E + P来逆转卵巢切除术后引起的子宫内膜变化。本研究共使用了27只成年雌性大鼠。这些动物被随机分为七个不同的组：第1组动物作为完整对照组，第2组和第6组动物进行了卵巢切除，第3组和第7组进行了卵巢切除（OVX）并植入了负载E（20 mg负载TCPL）的TCPL，第4组进行了OVX并植入了E（TCPL，20 mg）+ P（TCPL，40 mg）进行治疗。第5组动物作为完整对照组。每两周采集一次血样，持续47天。在整个研究过程中每天采集阴道涂片并进行检查。对生殖器官以及重要器官进行了组织病理学评估（苏木精和伊红染色）。从本研究中获得的数据表明如下：（I）卵巢切除导致总体重增加，然而E和E + P将体重维持在卵巢切除术前的水平，（II）持续递送E导致阴道上皮成熟，植入后72小时末涂片显示发情期，并在研究期间持续这种趋势，（III）E + P治疗未诱导发情，上皮变化类似于卵巢切除组，并且（IV）与卵巢切除组和完整对照组相比，E和E + P治疗导致丙二醛水平存在显著差异（P < 0.05）。本研究结果得出结论，TCPL持续递送E和E + P可用于维持生殖器官的正常功能，并可作为雌激素缺乏患者的一种有效且安全的治疗方法。
