基质金属蛋白酶-9在动脉粥样硬化血管中的异常表达

Aberrantly expressing of matrix metalloproteinase-9 in atherosclerotic aorta

目的了解基质金属蛋白酶-9在Apo-E基因敲除小鼠的动脉粥样硬化斑块血管中的表达。方法 8只5周龄,雄性SPF级C57BL/6J小鼠为对照组(NS组)。8只相同周龄,雄性SPF级载脂蛋白E基因敲除(C57BL/6J-ApoE-/-)小鼠为实验组(FS组)。高脂(1%胆固醇+15%猪油)喂食15周,20周龄取材检测。结果 FS组和NS组体重分别为(29.10±2.53)g和(33.20±5.18)g,差异无统计学有意义(P>0.05)。FS组较NS组血清总胆固醇显著增高,分别为(13.52±1.58)mEq/L和(2.12±0.35)mEq/L,差异有统计学有意义(P<0.01)。NS组主动脉管壁正常,无AS斑块;FS组主动脉出现典型的AS斑块,胶原纤维明显减少。免疫组化显示NS组可见主动脉血管内、中膜MMP-9呈散在弱阳性表达;而其在FS组则是内膜表达明显增高,呈强阳性表达。FS组主动脉弓MMP-9在mRNA及蛋白水平的表达较NS组均明显增高。mRNA平均光密度值为(11.61±1.92)和(1.52±0.40),差异有统计学意义(P<0.05);蛋白平均光密度值为(190.40±102.71)和(40.19±26.83),差异有统计学有意义(P<0.01)。结论在高脂喂食的载脂蛋白E基因敲除小鼠动脉粥样硬化模型中,MMP-9高表达可能与动脉粥样硬化斑块的形成和胶原纤维明显减少有关。

Objective To study the expression of Matrix Metalloproteinas-9 on atherosclerotic aorta in apo-E gene knockout mice. Methods Eight five-week-old male mice grade of SPF C57BL/6J were grouped as the control group（NS group）.Eight male grade of SPF C57BL/6J apo-E gene knockout mice of the same age were grouped as the experimental group（FS group）.Two groups of mice were fed with high fat diet for fifteen weeks（l% cholesterol＋15% lard）.Some test were done when the mice were twenty weeks. Results No significant difference could be found in the body weight between FS and NS group（29.10± 2.53）g and（33.20±5.18）g,P 〉 0.05.Serum total cholesterol was significantly higher in the FS group than in the NS group（13.52 ± 1.58）mEq/L and（2.12 ± 0.35）mEq/L,P 〈 O.Ol.It was normal and no atherosclerotic plaque could be seen in aortic intima in the NS group,but typical atherosclerotic plaque could be seen and collagen fibers was significantly decreased in the FS group.It was found in the immunohistochemical detection that the expression of MMP-9 was scattering weakly positive in aortic intima and media in the NS group,hut it was strongly positive in the FS group. The expression of MMP-9 on mRNA and protein levels in aortic arch was significantly higher in the FS group than in the NS group,mRNA IOD（1 1.61±1.92）and（1.52±0.40）,P 〈0.05.Protein IOD（190.40 ± 102.71）and （40.19± 26.83）,P 〈 0.01. Conclusion The slrong expression of MMP-9 is likely to be concerned with the formation of atherosclerotic plaque and the significant decrease of collagen fibers in the atherosclerosis model that apo-E gene knockout mice are fed with high fat diet.