In the ApoE^-/- mouse model of atherosclerosis （AS） stable plaque, the expression and location of intracellular tissue factor （TF） in the cellular components of AS stable plaque were investigated in order to explo...In the ApoE^-/- mouse model of atherosclerosis （AS） stable plaque, the expression and location of intracellular tissue factor （TF） in the cellular components of AS stable plaque were investigated in order to explore the cellular mechanism of AS thrombosis. Pathological changes of the stable plaque were observed under a microscope. The expression of TF protein was examined in aortic stable plaque of mice by using immunohistochemistry. Color image planimetric system was used to analyze the histological components of the stable plaque and the TF distribution. Under the confocal microscope, the intracellular TF location in the stable plaque of mice was observed. The results showed the cellular area was the major part of stable plaque （67.36%±6.52%, P〈0.01）. The percentage of total area occupied by cellular area was significantly larger than atheromatous gruel and acellular area （P〈0.01）. Macrophages and smooth muscle cells （SMC） were major cells in the cellular area. The percentage of total area occupied by SMC was significantly larger than by macrophages （P〈0.01）. Multiple linear regression analysis showed there was a positive correlation between TF area and SMC area （r=0.616, P=-0.008）, and no correlation was found between TF area and macrophage area （r=0.437, P=0.08）. Pictures of color image planimetric analysis of TF and SMC were merged to highlight areas with co-localization （yellow）, it was concluded that the process could be a cell-mediated TF expression in the stable plaque. SMC may be the major source of TF in AS without plaque rupture.展开更多
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
基金supported by a grant from the National Natural Sciences Foundation of China(No.30200109)
文摘In the ApoE^-/- mouse model of atherosclerosis （AS） stable plaque, the expression and location of intracellular tissue factor （TF） in the cellular components of AS stable plaque were investigated in order to explore the cellular mechanism of AS thrombosis. Pathological changes of the stable plaque were observed under a microscope. The expression of TF protein was examined in aortic stable plaque of mice by using immunohistochemistry. Color image planimetric system was used to analyze the histological components of the stable plaque and the TF distribution. Under the confocal microscope, the intracellular TF location in the stable plaque of mice was observed. The results showed the cellular area was the major part of stable plaque （67.36%±6.52%, P〈0.01）. The percentage of total area occupied by cellular area was significantly larger than atheromatous gruel and acellular area （P〈0.01）. Macrophages and smooth muscle cells （SMC） were major cells in the cellular area. The percentage of total area occupied by SMC was significantly larger than by macrophages （P〈0.01）. Multiple linear regression analysis showed there was a positive correlation between TF area and SMC area （r=0.616, P=-0.008）, and no correlation was found between TF area and macrophage area （r=0.437, P=0.08）. Pictures of color image planimetric analysis of TF and SMC were merged to highlight areas with co-localization （yellow）, it was concluded that the process could be a cell-mediated TF expression in the stable plaque. SMC may be the major source of TF in AS without plaque rupture.
文摘目的探讨氧化苦参碱对高脂诱导胰岛素抵抗Apo E^(-/-)小鼠肝脂代谢相关基因的影响。方法 17只♂C57BL/6J小鼠作为对照组,给予正常饮食;68只♂Apo E^(-/-)小鼠,给予高脂饮食,饲养16周后,将小鼠分为模型组、氧化苦参碱低、中、高剂量组。给药8周,测定小鼠体重和一般生化指标。荧光定量PCR和Western blot方法检测肝组织LPL、FAT/CD36、CPT1、UCP2、SREBP-1c、FAS、ACC m RNA和蛋白表达水平。结果氧化苦参碱能不同程度的降低体重、FBG、TC、TG、FFA、FINS、HOMA-IR,升高GIR,改善胰岛素的抵抗。同时降低了LPL、FAT/CD36、UCP2、SREBP-1c、FAS、ACC m RNA和蛋白的表达水平,升高了CPT1表达水平。结论氧化苦参碱能够通过脂转运、氧化、合成3个环节较全面的调节肝脂质代谢,改善高脂诱导的Apo E^(-/-)小鼠的胰岛素抵抗。
基金supported by Science and Technology Planning Project of Guangdong Province(No.2013B021800291)Science and Technology Program of Guangzhou Municipal Government(No.2014Y2-00186)National Natural Science Foundation of China(No.81170280)
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.
