巨噬细胞浸润及相关基因的表达在早期腹主动脉瘤发病中的作用

目的　探讨早期腹主动脉瘤 (AAA)的发病机制。方法　猪胰弹力蛋白酶灌注入 4 0只Wistar大鼠的股动脉 ,建立大鼠AAA模型 ,分别于灌注后 3d、7d、14d、2 8d切取大鼠的动脉瘤标本 ,应用弹力纤维特殊染色、CD6 8(巨噬细胞的特异性抗原 )免疫组织化学染色观察不同时期动脉壁弹力纤维的损伤、巨噬细胞的浸润 ,用原位分子杂交方法观察单核细胞趋化蛋白 1(MCP 1)及基质金属蛋白酶 2 (MMP 2 )的mRNA表达。结果　动脉壁弹力纤维的损伤于灌注后 2周时最重 ,CD6 8蛋白于灌注后 2周表达最强烈 ,与其他时段相比差异有非常显著意义 (P <0 0 1) ;MCP 1、MMP 2mRNA表达于灌注后 1周、2周时达到高峰 ,分别为 31 5 %± 5 7%、35 2 %± 7 8% ,并显著高于其他时段。结论动脉壁巨噬细胞的浸润程度与MMP 2mRNA表达、动脉壁弹力纤维的损伤呈平行关系 ;MCP 1的mRNA表达作为一种始动因素 ,可诱导巨噬细胞的浸润 ,促进了AAA的发生、发展

Effects of macrophage infiltration and related gene expression on the pathogenesis of early abdominal aortic aneurysm

OBJECTIVE: To detect the pathogenic mechanism of early abdominal aortic aneurysm (AAA). METHODS: Pig elastinase was perfused into the abdominal aortae of 40 Wistar rats to construct AAA animal models. The diameter of abdominal aorta was measured and then the abdominal aorta was harvested from 10 rats on the postoperative days 3, 7, 14, and 28 respectively. The thoracic aorta was used as control. HE staining, elastic staining, and CD68 (macrophage specific antigen) immunohistochemical staining were used to detect the distribution of elastic fiber and macrophage infiltration in aortic tissue. In situ hybridization was applied to investigate the mRNA expression of monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-2 (MMP-2). RESULTS: Three days after the operation, the expansion of abdominal aorta began to be seen and peaked 2 weeks after operation. Disruption of elastic fiber began to be found in the wall of abdominal aorta since 3 approximately 7 days after operation, and reached the maximum 2 weeks postoperatively. CD68 positive cell was not found in the wall of normal thoracic aorta and began to be found in the wall of abdominal aorta 3 approximately 7 days after operation. The expression of CD68 protein peaked on the day 14 with a significant difference from that on day 3 (t = 5.13, P < 0.01). The number of CD58 positive cells was remarkably decreased 4 weeks after operation in comparison with that 2 weeks after operation (t = 4.27, P < 0.01). The mRNA expression rates of MCP-1 and MMP-2 in the wall of abdominal aorta were at their maximal values, (31.5 +/- 5.7)% and (35.2 +/- 7.8)%, on the postoperative days 7 and 14 respectively, significantly higher than those at other time points (all P < 0.01). The MCP-1 and MMP-2 positive cells began to decrease since the 4th postoperative week. CONCLUSION: Macrophage infiltration is parallel to MMP-2 mRNA expression and elastic fiber disruption in aortic tissue. MCP-1 mRNA expression, as a promoting factor, induces the macrophage infiltration, thus contributing to the development and progression of AAA.