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目的研究雌激素在大鼠腹主动脉瘤(AAA)形成中的作用,探讨雌激素对腹主动脉瘤抑制作用的机制。方法雄性 Wistar 大鼠20只,随机分为实验组、对照组各10只。实验组定期腹腔内注射雌二醇,对照组定期腹腔内注射生理盐水(NS),分别用弹性蛋白酶灌注肾下腹主动脉制成AAA 模型。14 d 后用放射免疫法检测血清雌二醇的含量,用免疫组织化学、实时荧光定量聚合酶链反应(Real-Time PCR)测定动脉瘤组织基质金属蛋白酶2、9(MMP-2、9)的 mRNA 及蛋白的表达。结果实验组与对照组比较雌二醇水平显著增高,P<0.01。其动脉瘤扩张率分别为(103±4)%和(172±13)%(P<0.01)、MMP-2 mRNA 的相对表达量分别为0.07±0.04和0.22±0.07(P<0.01)、MMP-9 mRNA 的相对表达量分别为1.4±0.7和7.4±2.8(P<0.01)、MMP-2的表达率分别为(22±3)%和(50±12)%(P<0.01)、MMP-9的表达率分别为(23±2)%和(45±10)%(P<0.01)。结论在腹主动脉瘤形成的过程中雌激素可能通过降低 MMP-2、9的 mRNA 表达、蛋白合成及减少炎性细胞浸润来抑制腹主动脉瘤的形成。
Objective To study the role of estrogen in the formation of abdominal aortic aneurysm (AAA) in rats and explore the mechanism of the inhibitory effect of estrogen on abdominal aortic aneurysm. Methods Twenty male Wistar rats were randomly divided into experimental group and control group with 10 rats each. The experimental group received regular intraperitoneal injection of estradiol and the control group received regular intraperitoneal injection of normal saline (NS). The AAA model was established by peritoneal perfusion with elastase. Serum estradiol levels were measured by radioimmunoassay 14 days later. The expression of matrix metalloproteinase 2, 9 (MMP-2, 9) in aneurysms was detected by immunohistochemistry and real-time quantitative polymerase chain reaction (Real- MRNA and protein expression. Results The estradiol level in experimental group and control group was significantly higher (P <0.01). The aneurysm expansion rates were (103 ± 4)% and (172 ± 13)%, respectively (P <0.01). The relative expression of MMP-2 mRNA was 0.07 ± 0.04 and 0.22 ± 0.07 The mRNA expression of MMP-2 and MMP-2 were respectively (1.4 ± 0.7 and 7.4 ± 2.8) (P <0.01) and (22 ± 3)% and -9 were (23 ± 2)% and (45 ± 10)%, respectively (P <0.01). Conclusion Estrogen may inhibit the formation of abdominal aortic aneurysm by decreasing the mRNA expression of MMP-2, MMP9 and decreasing the infiltration of inflammatory cells in the process of abdominal aortic aneurysm formation.