阿托伐他汀对ApoE基因敲除小鼠血清白细胞三烯浓度及动脉粥样硬化斑块的影响

目的研究阿托伐他汀对ApoE（-/-）动脉硬化模型小鼠血清白细胞三烯浓度的影响,探讨阿托伐他汀的抗动脉硬化机制。方法将ApoE（-/-）小鼠分为对照组（n=12）、动脉硬化模型组（n=12）、阿托伐他汀干预组（n=12）。检测3组ApoE（-/-）小鼠血清的白细胞三烯B4和白细胞三烯D4浓度、测量主动脉斑块校正面积并进行比较。结果对照组主动脉未见动脉硬化病变;动脉硬化模型组建模成功,见不稳定斑块;阿托伐他汀干预组较动脉硬化模型组动脉硬化病变显著减轻,斑块校正面积显著下降,差异有统计学意义（13.24%±3.08%vs.29.08%±6.46%,P〈0.001）。动脉硬化模型组的血清白细胞三烯B4、白细胞三烯D4浓度显著高于对照组,差异有统计学意义[（34.79±4.47）ng.mL-1vs.（12.07±2.35）ng.mL-1,P〈0.001;（2 862.48±48.77）n.L-1vs.（2 357.10±53.57）ng.L-1,P〈0.001）]。阿托伐他汀干预组血清白细胞三烯B4、白细胞三烯D4浓度显著低于动脉硬化模型组,差异有统计学意义[（20.93±2.19）ng.mL-1vs.（34.79±4.47）ng.mL-1,P〈0.001;（2 592.06±22.45）ng.L-1vs.（2 862.48±48.77）ng.L-1,P〈0.001）]。结论阿托伐他汀可能通过降低血清白细胞三烯B4和白细胞三烯D4浓度,减轻炎症反应,稳定斑块,发挥抗动脉硬化作用。

Effect of atorvastatin on concentrations of serum leukotrienes and atherosclerosis in ApoE knock out mice

Objectives To investigate effect of atorvastatin on concentrations of serum leukotriene B4(LTB4) and leukotriene D4(LTD4) in ApoE(-/-) mouse model of atherosclerosis,and to reveal the anti-atherosclerosis mechanism of atorvastatin.Methods Thirty six 8-weeks-old ApoE(-/-) mice were randomized into control group(n=12,normal diet),atherosclerotic model group(n=12,high fat diet) and atorvastatin group(n=12,high fat diet and atorvastatin).Corrected plaque areas(PA/LA)and concentrations of serum LTD4 and LTB4 in ApoE(-/-) mice were measured and compared among the 3 groups.Results Atherosclerosis was not found in control group.Vulnerable plaques were discovered in atherosclerotic model group.Atherosclerotic lesion and corrected plaque area in atorvastatin group were significantly decreased compared with those in atherosclerosis model group(13.24%±3.08% vs.29.08%±6.46%,P<0.001).Concentrations of serum LTB4 and LTD4 in atherosclerosis model group were significantly higher than those in control group [(34.79±4.47)ng·mL-1 vs.(12.07±2.35)ng·mL-1,P<0.001;(2 862.48±48.77) ng·L-1 vs.(2 357.10±53.57)ng·L-1,P<0.001].Concentrations of Serum LTB4 and LTD4 in atorvastatin group were obviously lower than those in atherosclerosis model group [(20.93±2.19) ng·mL-1 vs.(34.79±4.47) ng·mL-1,P<0.001;(2 592.06±22.45)ng·L-1 vs.(2 862.48±48.77) ng·L-1,P<0.001].Conclusions Atorvastatin can play an important role in anti-atherosclerosis and enhances plaque stability by decreasing the concentrations of serum LTB4 and LTD4.