丹参酮ⅡA抑制腹主动脉瘤扩张的动物实验研究

Tanshinone Ⅱ A attenuates the development of elastase-induced abdominal aortic aneurysm of rat

目的研究丹参酮ⅡA对实验性大鼠腹主动脉瘤的抑制作用。方法SD雄性大鼠36只随机平均分成实验组、对照组、空白组。实验组与对照组予胰弹力蛋白酶灌注肾下段腹主动脉，空白组予生理盐水灌注。实验组全程腹腔内注射丹参酮ⅡA2mg／d，对照组与空白组予生理盐水腹腔内注射。术前和术后第5、12、18、24天使用多普勒超声测量动脉瘤最大处内径并测量动脉收缩压。术后24d取腹主动脉观察组织学变化并通过免疫组化、Western blot法、RT—PCR方法进行分析。结果术后24d实验组腹主动脉瘤直径较对照组明显减小[（0．210±0．002）cm比（0．304±0．004）cm，t=78．858，P=0．000]，但各组血压手术前后无明显变化（t=-1．237～-1．221，P〉0．05）。实验组标本弹性纤维含量明显高于对照组（0．469±0．040比0．230±0．024，t=17．944，P=0．000），管壁结构较完整保存。实验组基质金属蛋白酶（MMP）-2与MMP-9在mRNA转录和蛋白质表达水平上均较对照组明下降（t=25．943，P=0．000；t=42．815，P=0．000），同时单核细胞趋化蛋白1（MCP-1）与诱导型一氧化氮合酶（iNOS）表达则明显较对照组减少（t=4．518，P=0．000；t=17．685，P=0．000）。结论丹参酮ⅡA可通过下调MMP-2和MMP-9表达、抑制MCP-1及iNOS合成，显著抑制实验动物腹主动脉瘤的扩张。

Objective To determine if tanshinone Ⅱ A （ Tan Ⅱ A） can influence the development of elastase-induced experimental abdominal aortic aneurysms （AAAs）. Methods Totally 36 male Sprague- Dawley rats were randomly distributed into three groups （12 in each group） ： Tan Ⅱ A group, control group, and sham group. Rats of Tan Ⅱ A and control groups underwent intra-aortic elastase perfusion to induce AAAs, while rats of sham-group were perfused with saline. Rats of Tan Ⅱ A-group received Tan ⅡA treatment （2 mg/d）. The luminal diameter of the aneurysm at the segment with maximum diameter were measured pre-perfusion and on the 4 time point after perfusion. Systolic blood pressnre was measured by tailcuff technique. Aortic tissue samples were obtained on 24 days after perfusion and evaluated by RT-PCR, Western blot, immunohistochemistry and Miller＇s elastin-Van Gieson＇s （EVG） staining. Results Twenty- four days after perfusion, Tan II A significantly reduced increased aortic size compared to control group （ （0. 210 ±0. 002） em vs. （0. 304 ±0. 004） cm, t =78. 858, P =0. 000） without affecting blood pressure （t = - 1. 237 to - 1.221, P 〉 0. 05）. The over-expression of matrix metalloproteinases （ MMP）-2/9 （ t = 25. 943, P =0. 000; t =42. 815, P =0. 000）, monocyte chemotactic protein-1 （ MCP-1 ） （ t =4. 518, P = 0. 000）, inducible nitric oxide synthase （iNOS） （t = 17. 685, P =0. 000） and the destruction of elastic fibers in aortic tissue of control group were significantly less than Tan Ⅱ A group （ 0. 469 ± 0. 040 vs. 0. 230 ± 0. 024, t = 17. 944, P = 0. 000）. Conclusion Tanshinone Ⅱ A attenuates the development of elastase-induced experimental AAAs possibly by down-regulating MMP-2/9, MCP-1 and iNOS expression.