李秀英，叶云（西南医科大学附属医院药学部，四川泸州646000）

·论著·

水飞蓟宾对巨噬细胞摄取氧化低密度脂蛋白的影响*

李秀英，叶云△
（西南医科大学附属医院药学部，四川泸州646000）

目的探讨水飞蓟宾对巨噬细胞源性泡沫细胞形成的影响及相关机制。方法以RAW264.7巨噬细胞为细胞模型，采用MTT法检测水飞蓟宾对巨噬细胞活性的影响；油红O染色观察水飞蓟宾对巨噬细胞摄取氧化低密度脂蛋白（oxLDL）的影响；Western blotting检测水飞蓟宾对巨噬细胞SR-A、CD36、c-fos、c-Jun蛋白表达的影响及c-Jun N端激酶抑制剂SP600125对水飞蓟宾减少巨噬细胞CD36蛋白表达的影响。采用SPSS10.0统计软件进行数据分析，并采用双尾t检验进行统计学意义评估。结果12.5、25.0、50.0μg/mL水飞蓟宾对巨噬细胞活性无影响；50.0μg/mL水飞蓟宾显著抑制巨噬细胞对oxLDL的摄取［抑制率为（80.0±1.8）%］，从而减少巨噬细胞源性泡沫细胞的形成；12.5、25.0、50.0μg/mL的水飞蓟宾剂量依赖性降低巨噬细胞CD36蛋白表达，12.5、25.0、50.0μg/mL的水飞蓟宾组CD36蛋白量为对照组的（0.60±0.06）、（0.45±0.07）、（0.10±0.06）倍，差异均有统计学意义（P＜0.05），但对SR-A蛋白表达无影响；水飞蓟宾剂量依赖性降低细胞核c-fos蛋白量，12.5、25.0、50.0μg/mL水飞蓟宾组细胞核c-fos蛋白量是对照组的（0.50±0.05）、（0.40±0.06）、（0.30±0.05）倍，差异均有统计学意义（P＜0.05）；SP600125与水飞蓟宾共同孵育巨噬细胞后，CD36蛋白量降低为对照组的（0.20±0.06）倍，与水飞蓟宾处理组比较，差异有统计学意义（P＜0.05）。结论水飞蓟宾可抑制巨噬细胞源性泡沫细胞的形成，且与抑制c-fos/CD36通路相关。

动脉粥样硬化；巨噬细胞；泡沫细胞；脂蛋白类，LDL；水飞蓟素

【Abstract】Objective To explore the effectsof Silibinin onmacrophage-derived foam cell formation and itsmechanisms. M ethods RAW 264.7 macrophagewas used as the cellmodel，the effectsof Silibinin on themacrophage viabilitywas examined by MTT；the oil-red O staining was used to observe the effects of Silibinin on the uptake of oxidized low density lipoprotein （oxLDL）inmacrophages；the effectsofSilibinin on SR-A，CD36，c-fos，c-Jun protein expression inmacrophages，and c-Jun N-terminalkinase inhibitor SP600125 on reduction of CD protein expression inmacroph ages were detected by using Western blotting. The datawere analyzed by using the SPSS10.0 statistical soft ware and the statistical significance was assessed by the two-tailed t test.Results 12.5，25.0，50.0μg/mL Silibinin had no effecton macrophage viability；50μg/mL Silibinin significantly inhibited the oxLDL up take by macrophages［inhibition rate of（80.0±1.8）%］，thus reduced the macrophage-derived foam cell for mation；12.5，25.0，50.0μg/mLSilibinin decreased themacrophage CD36 protein expression in a dose dependentmanner，the CD36 protein levels in 12.5，25.0，50.0μg/mLSilibinin groupswere（0.60±0.06），（0.45±0.07），（0.10±0.06）fold of the control group，the differences were statistically significant（P＜0.05），but with out affecting the SR-A protein expression inmacrophages；Silibinin decreased nuclear c-fos protein in a dose dependentmanner，the nuclear c-fos protein levels in 12.5，25.0，50.0μg/mL Silibinin groups were（0.50±0.05），（0.40±0.06），（0.30±0.05）fold of the controlgroup，the differences were statistically significant（P＜0.05）；after the co-incubation with macrophagesby SP 600125 and Silibinin，the CD36 protein levelwas further decreased to（0.20±0.06）times of the control group，compared with the Silibinin-treated group，the difference was statistically significant（P＜0.05）.Conclusion Silibinin could inhibit the formation of macrophage-derived foam cells，moreover which is possibly related with the inhibition ofc-fos/CD36 pathway.

【Key words】A therosclerosis；M acrophages；F oam cells；Lipoproteins，LDL；Silymarin

动脉粥样硬化是以动脉壁脂质聚集或炎症发生为特征的慢性疾病，是不稳定性心绞痛、心肌梗死的主要原因［1］。……