雷帕霉素对动脉粥样硬化小鼠斑块面积影响及机制探讨

Researching the mechanism of rapamycin on area of plaque in atherosclerotic mice

关键词:  动脉粥样硬化  斑块  雷帕霉素

Key words:  atherosclerosis  plaques  rapamycin

摘要:

[目的]探讨雷帕霉素对ApoE基因敲除小鼠动脉粥样硬化斑块面积影响及机制。[方法]选取30只雄性ApoE基因敲除（ApoE^-/-）小鼠为研究对象，将其随机分为模型组、雷帕霉素组、阳性药物（瑞伐他汀）组。高脂饮食12周后灌胃干预4周。处死后取主动脉斑块组织油红O和苏木精-伊红（HE）染色评估斑块脂质情况、斑块面积；采用酶联免疫吸附（ELISA）法测定外周血中促炎因子肿瘤坏死因子α（TNF-α）、γ干扰素（INF-γ）、白介素-6（IL-6）和转化因子β（TGF-β）、白介素-10（IL-10）表达情况。[结果]雷帕霉素组斑块面积明显小于模型组，差异有统计学意义（P<0.05）；在炎症因子方面，雷帕霉素组能有效降低外周血TNF-α、INF-γ、IL-6表达，增加IL-10、TGF-β表达，差异有统计学意义（P<0.05）。[结论]雷帕霉素可通过增加抗炎因子含量、降低促炎因子含量来调控炎症反应，进而抑制斑块发展，降低血管狭窄程度。

Abstract:

[Objiective] To explore the mechanism and effect of rapamycin on plaque in ApoE^-/- atherosclerotic mice.[Methods] ApoE^-/- mice were divided into three groups:model group, rapamycin group and rosuvastatin group. There groups were fed with high cholesterol lipid feeding about 12 weeks, and then were treated with intragastric administration about 4 weeks. After killing at the end of experiment, the samples of aorta were collected for HE staining and Oil red staining to evaluate lipid nuclear and the area of plaque, using ELISA evaluating the content of TNF-α, INF-γ, IL-6, TGF-β, IL-10 in the serum of peripheral blood.[Results] The area of plaque was measured by image analysis after HE was found that rapamycin group was obviously reduced than model group (P<0.05). In terms of inflammatory factors, content of TNF-α, INF-γ, IL-6 in rapamycin group was marked decreased than model group (P<0.05). However, the level of IL-10,TGF-β was obviously increased comparing with model group (P<0.05).[Conclusion] Rapamycin can shrink the area of plaque and then reduce degree of vascular stenosis, which mechanism may be related to regulate the inflammation response.