清道夫受体AI转基因小鼠对动脉粥样硬化具有易感性

Susceptibility of Atherosclerosis in Transgenic Mice Overexpressing Human Scavenger Receptor AI on Endothelial Cells

通过本室已建立的人清道夫受体AI转基因小鼠对动脉粥样硬化的易感性的研究 ,以阐明人清道夫受体在动脉粥样硬化中的作用。为此 ,用人清道夫受体转基因小鼠 (F3)的纯合子 (TghSR AI+ +)、杂合子 (TghSR AI+ )、聚合酶链反应阴性 (TghSR AI )和C57BL 6小鼠各 1 2只 ,喂高脂高胆固醇饲料 1 4周后 ,取动物心脏和主动脉 ,作连续石蜡切片或冰冻切片 ,HE染色或油红O染色 ,用图象分析系统测量和计算主动脉动脉粥样硬化病变面积。结果发现 ,喂高脂高胆固醇饲料 1 4周后 ,小鼠动脉粥样硬化病变主要位于主动脉窦至主动脉弓的区域内 ,但纯合子鼠的动脉粥样硬化病变除在整个主动脉根部外 ,病变已扩展到胸主动脉、冠状动脉和肾动脉。C57BL 6鼠和阴性小鼠的主动脉窦区瓣膜附着处仅有轻微损伤。计算机图象分析发现 ,纯合子鼠主动脉粥样硬化病变的平均面积为 1 4 4 864± 1 71 0 3μm2 ,与杂合子组 (1 1 1 32 2± 1 0 71 3μm2 )相比 ,差异有显著性统计学意义 (P <0 .0 5) ;与聚合酶链反应阴性 ( )小鼠或C57BL 6小鼠相比 ,差异有非常显著性统计学意义 (P <0 .0 1 )。提示纯合子鼠动脉粥样硬化病变最严重 ,其次是杂合子鼠 ,而非转基因小鼠主动脉动脉粥样硬化病变较轻。转基因小鼠肝、肾也可见明显的病变。

Aim To test whether the transgenic mice with expressed human SR AI on endothelial cells are susceptible to atherosclerosis on high fat high cholesterol diet (HFHC). Methods TghSR AI+/+, TghSR AI+/ , TghSR AI / from F3 mice and C57BL/6 mice were fed 1.25% cholesterol, 16% fat and 0.5% sodium cholate for 14 weeks. Tissues of heart and aorta, liver, kidney and others from control and transgenic mice were prepared for morphological analysis. To evaluate the degree of atherosclerosis in the transgenic and control mice, atherosclerotic lesions were quantified in the aortic root area with computer assisted image analysis system in all four groups. Results After animals were fed HFHC diet for 14 weeks, extensive atherosclerotic lesions were found at the junction of the aorta to the heart and the aortic sinus, including valve, valve commissures in the aortic wall of TghSR AI+/+ and TghSR AI+/ transgenic mice. Typical lesions of aorta in transgenic mice was stained with oil red O. In TghSR AI+/+ and TghSR AI+/ mice, the mean lesion area per section was 144 864±17 103 μm 2 and 111 323±10 713 μm 2, respectively, P<0.05 (n=6). In TghSR AI / and C57BL/6 mice, the mean lesion area per section was 79 887±9 228 μm 2 vs 66 305±7 991 μm 2, P>0.05 (n=6). However, the lesion area of TghSR AI+/+ and TghSR AI+/ mice was significantly higher than lesion area of TghSR AI / or C57BL/6 mice. Conclusions The transgenic mice are more susceptible to atherosclerosis than C57BL/6 on HFHC diet. These mice may be of value for use as an in vivo test system for studied of pharmacological or genetic interventions of atherosclerosis.