Esfandiari Navid, Khazaei Mozafar, Ai Jafar, Bielecki Ryszard, Gotlieb Lynda, Ryan Edward, Casper Robert F
Toronto Centre for Advanced Reproductive Technology, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Fertil Steril. 2007 Feb;87(2):257-62. doi: 10.1016/j.fertnstert.2006.06.040. Epub 2006 Nov 13.
To determine the inhibitory effect of a statin on angiogenesis in a three-dimensional (3-D) culture of human endometrial fragments in vitro. Angiogenesis has been proposed as an important mechanism in the pathogenesis of endometriosis, and statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) have been shown to have anti-inflammatory and anti-angiogenic activity.
Experimental in vitro study of human endometrial biopsies and 3-D culture in fibrin matrix.
Research laboratory at a university-affiliated infertility center.
PATIENT(S): Forty-six normal ovulating women undergoing infertility treatment.
INTERVENTION(S): Endometrial samples obtained from the fundus of the uterine cavity were minced, and the fragments were placed in a three-dimensional fibrin matrix culture system.
MAIN OUTCOME MEASURE(S): Presence or absence of proliferation of stromal cells and invasion of the fibrin matrix, presence or absence of vessel sprouting, and immunohistochemical characterization of cellular components.
RESULT(S): During the 1st week of culture, invasion of stromal cells into the fibrin matrix occurred in the control group and in some wells outgrowths were observed. After 2 weeks, endometrial glands were observed in the outgrowths at a distance from the main tissue and were growing in conjunction with new vessel formation until the end of culture period. A concentration-dependent effect of lovostatin was seen on cell growth and angiogenesis in the experimental groups. In the presence of 5 and 10 microM of statin, angiogenesis was abolished, and cell proliferation was inhibited. In the presence of 1 microM of lovastatin, angiogenesis was reduced, but cell proliferation was not affected.
CONCLUSION(S): The statins were shown to be effective in inhibiting the mechanisms of cell proliferation and angiogenesis in an experimental model for the development of endometriosis-like tissue.
在人子宫内膜碎片的三维（3-D）体外培养中确定他汀类药物对血管生成的抑制作用。血管生成被认为是子宫内膜异位症发病机制中的一个重要机制，并且他汀类药物（3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂）已被证明具有抗炎和抗血管生成活性。
人子宫内膜活检及在纤维蛋白基质中进行三维培养的体外实验研究。
大学附属不孕不育中心的研究实验室。
46名接受不孕治疗的正常排卵女性。
从子宫腔底部获取的子宫内膜样本被切碎，碎片被置于三维纤维蛋白基质培养系统中。
基质细胞增殖和纤维蛋白基质浸润的有无、血管芽生的有无以及细胞成分的免疫组织化学特征。
在培养的第1周，对照组出现基质细胞浸润到纤维蛋白基质中，并且在一些孔中观察到有生长物。2周后，在远离主要组织的生长物中观察到子宫内膜腺体，并伴随着新血管形成生长直至培养期结束。在实验组中观察到洛伐他汀对细胞生长和血管生成具有浓度依赖性作用。在存在5和10微摩尔他汀的情况下，血管生成被消除，细胞增殖受到抑制。在存在1微摩尔洛伐他汀的情况下，血管生成减少，但细胞增殖未受影响。
在子宫内膜异位症样组织发育的实验模型中，他汀类药物被证明可有效抑制细胞增殖和血管生成机制。
