血管生长抑素抑制小鼠胚胎植入的最低有效量及其作用机理  

Minimum effective dose and regulatory mechanism of angiostatin-inhibited embryo implantation in the mouse

作　　者：赵田夫[1] 张键[2] 李晶[2] 曹宇静[2] 李素敏[2] 周家喜[2] 段恩奎[2] 

机构地区：[1]保定师范专科学校生物系,河北071000 [2]中国科学院动物研究所生殖生物学国家重点实验室,北京100080

出　　处：《动物学报》2003年第3期332-338,共7页ACTA ZOOLOGICA SINICA

基　　金：国家自然科学基金 ( 30 170 35 7);国家 973项目 (TG19990 5 5 90 3);中国科学院知识创新工程前沿领域项目;中国科学院动物研究所创新工程项目;中国科学院创新研究基金资助~~

摘　　要：血管生长抑素是一种新的抑制血管生成的因子 ,它能够特异性地抑制血管生成。本文通过宫角注射法对血管生长抑素抑制小鼠胚胎植入的最低有效量进行了探讨 ,并通过明胶酶谱分析和免疫印迹等方法研究了不同剂量血管生长抑素对MMP 2和MMP 9活性及蛋白表达的影响。实验表明 ,宫角注射 4μg血管生长抑素是抑制小鼠胚胎植入的最低有效剂量 ,这一最低有效剂量显著抑制了小鼠子宫MMP 2和MMP 9的活性及蛋白的表达.Angiostatin, an internal proteolytic 38 kD cleavage product of plasminogen, has been shown to inhibit the process of angiogenesis or neovascularization. In the present study, we detected the minimum effective dose for angiostatin to inhibit embryo implantation using intra-uterine horn injection in the mouse, and analyzed the effect of angiostatin on MMPs activity and protein expression using gelatin zymography and Western blot. Our results show that different doses of angiostatin have different roles in inhibiting the number of implanted embryos. There was no significant decrease after 3 μg angiostatin treatment(P>0.05). Implanted embryos were significantly inhibited by 4 μg angiostatin at day 3(day 1=1st day on which vaginal plug observed)(P<0.05), and 5 μg or 6 μg angiostatin on day 4 or day 5. Both 5 μg and 6 μg angiostatin remarkably inhibited implanted embryos at day 3(P<0.05). We conclude that 4 μg is the minimum effective dose of angiostatin to inhibit embryo implantation at day 3 in the mouse. At the same time, we also detected the activity and protein expression of MMP-2 and MMP-9 in mouse uteri after different doses of angiostatin. Our results showed that 3 μg angiostatin had no effect on MMP-2 and MMP-9 activity and protein expression(P>0.05). But 4 μg, 5 μg or 6 μg angiostatin treatment significantly inhibited MMPs activity and expression at day 3(P<0.05). In summary, angiostatin might be an effective drug for inhibiting embryo implantation by inhibiting MMPs activity and blocking angiogenesis in the mouse uterus.

关 键 词：血管生长抑素 小鼠 胚胎植入 作用机理 基质金属蛋白酶 生殖 

分 类 号：Q813[生物学—生物工程]