雌激素在大鼠腹主动脉瘤形成中的作用

The role of estrogen in the formation and development of abdominal aortic aneurysm:experiment with rats

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 investigate the role of estrogen in the formation and development of abdominal aortic aneurysm （AAA）. Methods Twenty male Wister rats were randomly divided into 2 equal groups： experiment group, injected with 17-βestradiol （E2 ） intraperitoneally 1 week before the establishment of AAA once a day for 3 weeks （ until 2 weeks after the establishment of AAA）, and underwent infusion of pancreatic elastase into the infrarenal abdominal aorta through a catheter inserted into the left common iliac artery o as to establish the AAA model, and control group, injected with normal saline intraperitoneally for 3 weeks. Two weeks after the establishment of AAA model, the rats underwent laparotomy, blood samples were collected from vena cava inferior to detect the level of E2 by radioimmunoassay and then the aneurysms were harvested to undergo immunohistochemistry and real-time PCR to detect the protein expression and mRNA expression of matrix metalloproteinase （MMP） -2 and MMP- 9. Results The plasma E2 level of the experiment group was （28 ±6） pg/ml, significantly higher than that of the control group [ （5.86 ± 0.24） pg/ml, P 〈 0.01 ]. The aorta dilatation rate of the experiment group was （103 ±4）%, significantly lower than that of the control group [ （172 ±13）%, P 〈0.01]. The destruction of arterial wail, degradation of elastic fibers, and infiltration of inflammatory cells were all more severe in the control group than in the experiment group. The relative mRNA expression of MMP-2 of the experiment group was 0.07 ± 0.04, significantly lower than that of the control group （0.22 ± 0.07, P 〈 0. 01 ） ; and the relative mRNA expression of MMP-9 of the experiment group was 1.4 ± 0.7, significantly lower than that of the control group （ 7.4 ± 2. 8, P 〈 0.01 ）. The protein expression of MMP-2 of the experiment group was （22 ±3）%, significantly lower than that of the control group [ （50 ± 12）%, P 〈 0. 01 ], and the protein expression of MMP-9 of the experiment group was （23 ± 2） %, significantly lower than that of the control group too [ （45 ± 10） %, P 〈 0. 01 ]. Conclusions Estrogen inhibits the AAA formation and development by reducing the MMP-2 and MMP-9 mRNA and protein expression and the infiltration of inflammatory cells.