L-4F 与辛伐他汀联合使用可刺激胆固醇外流和相关蛋白表达，从而减少载脂蛋白 E 基因敲除小鼠的动脉粥样硬化病变。

The combination of L-4F and simvastatin stimulate cholesterol efflux and related proteins expressions to reduce atherosclerotic lesions in apoE knockout mice.

机构信息

Department of Cardiology, Zhongshan hospital, Sun Yat- Sen University, Zhongshan, Guang Dong, China.

出版信息

Lipids Health Dis. 2013 Dec 8;12:180. doi: 10.1186/1476-511X-12-180.

BACKGROUND

Both L-4F, one apolipoprotein A-1 mimetic peptide, and statins can reduce progression of atherosclerosis by different mechanisms. The combination of the two drugs can cause lesion regression by rendering HDL anti-inflammatory. We postulated that combination of L-4F and simvastatin may stimulate cholesterol efflux and related proteins expressions to alleviate atherosclerosis.

METHODS

Thirty male wild-type (W-T) C57 BL/6 mice and apo E(-/-) mice were divided into five groups: W-T group, atherosclerosis (AS) group, simvastatin group, L-4F group and the combination of simvastatin and L-4F group. After 16 weeks, serum lipids, atherosclerotic lesion areas, cholesterol efflux and the expressions of related proteins including ABCA1, SR-BI, ABCG1, LXRα and PPARγ were evaluated.

RESULTS

The aortic atherosclerotic lesion areas were reduced more significantly by combination of both drugs than single agent, and cholesterol efflux was promoted more in combination group than simvastatin and L-4F group. Besides, the combination group promoted expressions of cholesterol efflux related proteins.

CONCLUSIONS

The combination of L-4F and simvastatin reduced atherosclerotic lesions, which stimulates cholesterol efflux by promoting the expressions of related proteins. In addition, these results help us further understand that the regression of the atherosclerosis would be assessed by reduction in LDL-C with increase of cholesterol efflux.

背景

载脂蛋白 A-1 模拟肽 L-4F 和他汀类药物均可通过不同机制减缓动脉粥样硬化的进展。两种药物的联合使用可以通过使 HDL 具有抗炎作用来导致病变消退。我们推测，L-4F 和辛伐他汀的联合使用可能会刺激胆固醇流出和相关蛋白的表达，从而缓解动脉粥样硬化。

方法

将 30 只雄性野生型（W-T）C57BL/6 小鼠和载脂蛋白 E（-/-）小鼠分为五组：W-T 组、动脉粥样硬化（AS）组、辛伐他汀组、L-4F 组和辛伐他汀与 L-4F 联合组。16 周后，评估血清脂质、动脉粥样硬化病变面积、胆固醇流出和相关蛋白（包括 ABCA1、SR-BI、ABCG1、LXRα 和 PPARγ）的表达。