丹参酮ⅡA抑制腹主动脉瘤基质金属蛋白酶-2及诱导型一氧化氮合酶的研究  

Inhibitory effects of tanshinone lI A on the expression of matrix metalloproteinases-2 and inducible nitric oxide synthase in experimental abdominal aortic aneurysm

作　　者：商弢[1] 刘昭[1] 周敏[1] 刘长建[1] 

机构地区：[1]南京大学医学院附属鼓楼医院血管外科,210008

出　　处：《中华实验外科杂志》2012年第4期605-608,共4页Chinese Journal of Experimental Surgery

基　　金：江苏省自然科学基金资助项目（BK2009035）

摘　　要：目的观察丹参酮ⅡA对胰弹力蛋白酶灌注制作的大鼠腹主动脉瘤（AAA）模型中基质金属蛋白酶-2（MMP-2）和诱导型一氧化氮合酶（iNOS）的抑制作用。方法将SD雄性大鼠36只随机分成实验组、对照组、空白组3组，每组12只。实验组与对照组应用胰弹力蛋白酶灌注方法制作AAA模型，空白组给予生理盐水灌注。实验组全程接受腹腔内注射丹参酮ⅡA2mg／（天·只），对照组与空白组给予生理盐水注射。术前和术后第5、12、18、24天使用彩色超声仪测量动脉瘤最大处内径，并测量动脉收缩压。术后24d取腹主动脉组织标本观察组织学变化，应用免疫组织化学、Western blot、逆转录-聚合酶链反应（1iT-PCR）方法进行定量观察。结果术后第1周起实验组腹主动脉直径明显小于对照组（P〈0．01），且各组血压无明显变化（P〉0．05）。实验组标本中弹力纤维含量明显高于对照组（P〈0．01），而MMP-2和iNOS蛋白表达则明显较对照组减少（P〈0．01）。实验组MMP-2mRNA表达较对照组明显抑制（P〈0．01）。结论丹参酮ⅡA能够通过下调MMP-2和iNOS表达而抑制大鼠AAA的扩张。Objective To determine if tanshinone Ⅱ A （Tan Ⅱ A）, one of the major lipophilic components of Salvia miltiorrhiza Bunge （ SM）, can inhibit the development of elastase-induced experimental abdominal aortic aneurysms （AAAs） by down-regulating the expression of matrix metalloproteinases-2 （MMP-2） and inducible nitric oxide synthase （iNOS）. Methods Male Sprague-Dawley rats （n = 12/each group） were randomly divided into three groups： Tan ⅡA, control, and sham operation. Rats in Tan ⅡA and control groups underwent intra-aortic elastase perfusion to induce AAAs, and those in sham operation group were perfused with saline. Rats in Tan ⅡA group were given Tan Ⅱ A （2 mg/per rat-day）. The luminal diameter of the aneurysm at the segment with maximum diameter was measured pre-perfusion and on the 5th, 12th, 18th and 24th day after perfusion. Systolic blood pressure was measured by tail-cuff tech-nique. Aortic tissue samples were obtained on the 24th day after perfusion and evaluated by reverse tran- scription-polymerase chain reaction （RT-PCR）, Western blotting, immunohistocbemistry and Miller＇ s elastin-Van Gieson＇ s （EVG） staining. Results At 24th day after perfusion, rats in control group had significantly increased aortic sizes versus sham operation group （P 〈 0. 01 ）, while Tan Ⅱ A significantly reduced this increase （ Tan ⅡA group vs control group, P 〈 0. 01 ） without affecting blood pressure （ P 〉 0. 05）. The over-expression of MMP-2, iNOS and MMP-2 mRNA, and the destruction of elastic fibers in aortic tissue of control group were significantly decreased by Tan Ⅱ A （P 〈 0. 01 ）. Conclusion Tan Ⅱ A inhibits the development of elastase-induced experimental AAAs possibly by suppressing MMP-2 and iNOS, which may offer a new pharmacological therapy for AAAs.

关 键 词：腹主动脉瘤 丹参酮 基质金属蛋白酶-2 一氧化氮合酶 

分 类 号：R285.5[医药卫生—中药学]