大鼠血清高密度脂蛋白对动脉粥样硬化的抵抗作用

Resistant effects of serum high density lipoprotein reserve on atherosclerosis in rat

目的探讨大鼠血清高密度脂蛋白(HDL)对动脉粥样硬化(AS)的抵抗作用及可能机制。方法将24只体质量在200 g左右的SD大鼠随机分为实验组和对照组,每组各12只,均行胸腹主动脉球囊血管成形术,实验组术前1周开始给予高脂喂养。取术前1周、术后2周和6周大鼠静脉血做血脂检测,行胸主动脉组织形态学分析,行免疫组化染色检测三磷酸腺苷结合盒转运子A1(ABCA1)的表达。结果 (1)实验组高脂喂养后血清低密度脂蛋白胆固醇(LDL-C)显著增高,高密度脂蛋白胆固醇(HDL-C)轻度升高,HDL-C/LDL-C比值由高脂喂养前的(6.21±0.87)降至术后2周的(0.70±0.25)和术后6周的(0.30±0.05),呈时间依赖性下降(均为P<0.05)。(2)术后2周,两组均可见胸主动脉内弹力板断裂,新生内膜形成,实验组见内膜脂质沉积,但未见脂质斑块形成;术后6周,实验组可见新生内膜增厚明显,并粥样斑块形成,内膜/中膜面积百分比和管腔面积狭窄率均大于对照组,但差异无统计学意义(11.85%±4.86%比9.13%±7.66%,3.39%±1.50%比2.59%±2.12%,均为P>0.05)。(3)双因素相关分析,内膜/中膜面积百分比和管腔面积狭窄率与HDL-C/LDL-C比值均呈负相关。(4)实验组术后2周和6周血管内膜及中膜ABCA1表达水平均高于对照组[2周:(50.5±3.1)比(38.8±2.5);6周:(35.6±2.8)比(20.4±5.1),P均<0.05]。结论大鼠具有很高的血清HDL储备能力,在一定时间内,具有抵御高LDL-C致AS的作用,其机制可能与血清高HDL水平促进ABCA1表达,增强血管壁泡沫细胞胆固醇逆转运和延缓粥样斑块形成有关。

Objective To investigate the resistant effects and mechanisms of serum high density lipoprotein cholesterol （HDL-C） in rat atherosclerosis. Methods A total of 24 Sprague-Dawley rats were randomly divided into control group and experimental group. Balloon catheter was used to injure the intima of thoracic and abdominal aorta. The experimental group was fed with high fat diet and serum lipids were detected. Thoracic aorta was isolated and prepared for hematoxylin-eosin and immunohistochemistry staining 2 or 6 weeks after intima injure. Results （ 1 ） The levels of serum LDL-C were significantly increased from （0. 19± 0. 09 ） mmol/L at baseline to （2.35±0. 85 ） mmol/L and （17. 17 ±1.83） mmoL/L HDL-C/LDL-C ratio was significantly decreased from （6. 21 ±0. 87） at baseline to （0. 70±0. 25） at 2 weeks and （0. 30 ± 0. 05 ） at 6 weeks in experiment group （ both P 〈 0. 05 ）. （2） No typical atheromatous plaques except for the neointima and ruptured internal elastic membrane appeared 2 weeks after intima injure, moreover, neointima thickness and typical atheromatous plaques were presented after 6 weeks. Area ratio of intima/tunica media and stenosis of lumina in experimental group were increased compare with control group at 6 weeks （ll. 85% ± 4. 86% vs. 9. 13% ±7. 66% , 3.39% e 1.50% vs. 2. 59%±2. 12% , P 〉0. 05）. （3） Correlation analysis showed that there was a negative correlation between intima/media area ratio and stenosis of lumina and HDL-C/LDL-C ratio. （4） Expressions of ABCA1 and MCP-1 in the neointima and media in experimental group were significantly increased than in control group at 2, 6 weeks [2w：（50.5±3.1） vs. （38.8±2.5）; 6w：（35.6±2.8） vs. （20.4±5.1）, allP〈0.05]. Conclusions The high serum HDL-C level in rats can decrease atherosclerosis to a certain extent by overexpression of ABCA1 for cholesterol counter transport.