Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clo...Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clopidegrol on the development of atherosclerosis, accumulation of lipid- filled macropha-ges in apoE null mice. Methods All mice were done cuffed common carotid artery and fed a Western-type atherogenic diet for 6 weeks from the day of surgery, at same time the therapy group mice were gavaged S18886 5 mg/Kg/day and clopidegrol respec- tively, the same volume water were gavaged as the placebo group. Results profound inhibition of lesion area growth after cuff of the right common carotid artery in mice with 5 mg/kg of S18886, markdely reduce intima to media ratio and intima to total wall area compare with clopidegrol or blank group; Macrophage infiltration into sites of arterial plaque was also markedly attenuated by ICAM-1 deficiency in the S18886 group, whereas inside the arterial wall plaque of placebo apoE null mice α-smooth muscle actin markedly attenuated. Treatment with 25 mg/kg/day clopidegrol reduced the level of ICAM-1 stai ning, both S18886 and clopidegrol didn't influence the α-smooth muscle actin inside plaque. Conclusions It was considered that the novel anti-thrombotic drug significant reduce macrophage infiltration in the sites of arterial plaque by ICAM-1 deficiency, S18886 not only reduce the size, but also stabilized the plaque.展开更多
目的探讨E1A激活基因阻遏子(CREG)在动脉粥样硬化(AS)血管中的表达及其与炎症因子的关系。方法 Apo E(-/-)小鼠6周龄断奶后给予高脂喂养。8周后取主动脉血管,采用HE染色观察血管的形态学变化;采用免疫荧光染色观察CREG、SMα-actin和巨...目的探讨E1A激活基因阻遏子(CREG)在动脉粥样硬化(AS)血管中的表达及其与炎症因子的关系。方法 Apo E(-/-)小鼠6周龄断奶后给予高脂喂养。8周后取主动脉血管,采用HE染色观察血管的形态学变化;采用免疫荧光染色观察CREG、SMα-actin和巨噬细胞标志物Mac-3的表达变化。取高脂喂养的1~8周小鼠血管,采用Western blot方法检测AS血管中CREG及核转录因子(NF)-κB的表达的变化。结果在Apo E(-/-)小鼠高脂喂养8周,主动脉血管AS斑块明显形成,斑块内有胆固醇结晶,斑块凸凹不平,管腔明显狭窄。免疫荧光显示AS血管中,CREG表达明显下降,同时SMα-actin表达也下降,而Mac-3表达增高。Apo E(-/-)小鼠高脂喂养2~8周,取动脉血管行蛋白定量分析,结果显示高脂喂养2周时,CREG在动脉血管中的表达不是降低,而是明显升高,高脂喂养第4周,CREG表达急剧下降,而后又逐渐上升,但不能升至正常水平。同时NF-κB随着时间的推移,表达逐渐升高。结论在AS进程中,血管中膜的VSMCs由收缩表型向合成表型转化,细胞增生活跃、分化减弱,CREG作为维持VSMCs分化的蛋白,在血管中的表达与AS进展密切相关,同时伴随着炎症因子表达逐渐升高。展开更多
文摘Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clopidegrol on the development of atherosclerosis, accumulation of lipid- filled macropha-ges in apoE null mice. Methods All mice were done cuffed common carotid artery and fed a Western-type atherogenic diet for 6 weeks from the day of surgery, at same time the therapy group mice were gavaged S18886 5 mg/Kg/day and clopidegrol respec- tively, the same volume water were gavaged as the placebo group. Results profound inhibition of lesion area growth after cuff of the right common carotid artery in mice with 5 mg/kg of S18886, markdely reduce intima to media ratio and intima to total wall area compare with clopidegrol or blank group; Macrophage infiltration into sites of arterial plaque was also markedly attenuated by ICAM-1 deficiency in the S18886 group, whereas inside the arterial wall plaque of placebo apoE null mice α-smooth muscle actin markedly attenuated. Treatment with 25 mg/kg/day clopidegrol reduced the level of ICAM-1 stai ning, both S18886 and clopidegrol didn't influence the α-smooth muscle actin inside plaque. Conclusions It was considered that the novel anti-thrombotic drug significant reduce macrophage infiltration in the sites of arterial plaque by ICAM-1 deficiency, S18886 not only reduce the size, but also stabilized the plaque.
