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特拉唑嗪对载脂蛋白E基因敲除小鼠动脉粥样硬化的影响 被引量:2

Effects of Terazosin on atherosclerosis development in apolipoprotein E knockout mice
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摘要 目的探讨特拉唑嗪对载脂蛋白E基因敲除(apoE-/-)小鼠动脉粥样硬化的影响及其机制。方法将24只8周龄apoE-/-小鼠随机分为正常饮食组(n=8)、高脂饮食对照组(n=8)和高脂饮食特拉唑嗪组(n=8)。12周后眼眶静脉取血监测各组血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)含量及白细胞介素.6(IL-6)水平。取主动脉标本行油红O染色,提取蛋白行Western blot实验检测各组信号传导与转录激活因子3(STAT3)、p-STAT3、单核细胞趋化蛋白-1(MCP-1)表达。结果高脂饮食大鼠主动脉内膜的粥样斑块面积明显增加[(18.14±3.41)%比对照组的(5.00±2.21)%)],而特拉唑嗪明显抑制斑块形成[(13.23±1.98)%]。高脂组血TC[(18.854±3.44)mmol/L]、LDL-C[(16.114±5.10)mmol/L]明显高于正常对照组[TC:(2.32±1.10)mmoL/L;LDL-C:(3.95±1.41)mmol/L],给予特拉唑嗪后能明显降低两者水平[TC:(12.90±3.02)mmol/L;LDL-C:(9.60±3.11)mmoL/L];特拉唑嗪可以明显降低高脂诱导的IL-6的升高[(12.84±2.74)ng/L比动脉粥样硬化组(17.514±4.98)ng/L]。比较于正常饮食组,高脂饮食组p-STAT3(1.394±0.28)和MCP-1(0.64±0.12)均明显高于正常对照组(p-STAT3:0.74±0.09;MCP-1:0.28±0.11)且特拉唑嗪组(P-STAT3:0.894±0.11;MCP-1:0.26±0.06)明显低于高脂饮食组。结论特拉唑嗪能够降低TC、LDL-C,具有一定的抗动脉粥样硬化作用,其机制除了降脂作用以外,还可能与抑制IL-6介导的m管局部炎症及MCP-1表达有关。 Objective To explore the effects and mechanisms of Terazosin on atherosclerosis de- velopment in apolipoprotein E (apoE) -/- mice. Methods Twenty-four eight-weeks-old apoE -/- mice were divided into three groups randomly : normal control group ( n = 8 ) was fed on common breeding diet ; high fat group was fed on western-type diet; while Terazosin group received a western-type diet and Terazosin [ 1 mg/(kg.d) 1- After 12 weeks mice were sacrificed. Serum totalcholesterol (TC) , low density lipopro tein-cholesterol (LDL-C), interleukin (IL)-6 levels, signal transducer and activator of transcription 3 (STAT3) , p-STAT3, and monocyte chemoattractant protein (MCP)-1 in the arota were determined. The percentage of aorta sinus plaque to lumen area was measured using oil red O staining. Results The area of aorta sinus plaque in high-fat group [ ( 18.14 ± 3.41 ) % ] was increased as compared with normal control group [ (5.00± 2. 21 )%]. Terazosin addition could reduce the serum lipids (TC and LDL-C) [ TC in high-fat group: ( 18.85 ±3.44) mmo]/L, and in Terazosin group: ( 12. 90± 3.02) mmol/L; LDL-C in high-fat group: (16. 11 ±.10) mmoL/L, and in Terazosin group: (9. 60 ± 3.11 ) mmol/L] and pro-in flammation cytokines IL-6 [ in high-fat group: (17.51 ±4. 98) ng/L, and in Terazosin group: (12. 84 ±2.74) ng/L] , which resulted in less area of aorta sinus [ ( 13.23 ± 1.98)% ]. Meanwhile, the elevated p-STAT3 and MCP-1 in the aorta induced by IL-6 could be reversed by Terazosin (p-STAT3 in high-fat group: 1.39 ±0. 28, and in Terazosin group: 0. 89 ±0. 11 ; MCP-1 in high-fat group: 0. 64 ±0. 12, and in Terazosin group: 0. 26 ± 0. 06). Conclusion Terazosin could inhibit the develpment of atherosclerosis via inhibitin~ inflammatory resnonse which was induced bv II-6-STAT3-MCP-1 axis.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2014年第4期713-715,共3页 Chinese Journal of Experimental Surgery
基金 武汉市科技局关键技术攻关资助项目(2013060602010256)
关键词 特拉唑嗪 动脉粥样硬化 白细胞介素-6 信号传导与转录激活因子3 单核细胞趋化蛋白一1 Terazosin Atherosclerosis Interleukin-6 Signal transducer and activator oftranscription 3 Monocyte chemoattractant protein-1
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