辛伐他汀通过抑制TLR4信号通路调节血管平滑肌细胞炎症因子的表达
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Simvastatin Regulate the Expressions of Inflammatory Factors by Inhibiting the Activation of TLR4 Signaling in Vascular Smooth Muscle Cells
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    摘要:

    目的通过检测血管平滑肌细胞(VSMC)炎症因子白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)及相关炎症信号分子的表达,探讨辛伐他汀在氧化型低密度脂蛋白(ox-LDL)诱导VSMC炎症反应中的作用和机制。方法体外培养大鼠VSMC,经Toll样受体4(TLR4)阻断剂抗TLR4抗体及辛伐他汀预处理,使用ox-LDL进行干预,用逆转录聚合酶链反应检测TLR4mRNA的表达,通过酶联免疫吸附法检测细胞培养上清液中炎症因子IL-6及TNF-α的水平。结果ox-LDL可以增加VSMC对IL-6及TNF-α的表达,预先经TLR4阻断剂干预后,IL-6及TNF-α的表达明显下调,与未阻断剂组相比,差异皆有统计学意义(P<0.01);不同浓度的辛伐他汀可以剂量依赖性的抑制TLR4mRNA的表达(P<0.01),同时也可以剂量依赖性的抑制IL-6及TNF-α的表达(P<0.05);预先经TLR4阻断剂干预后,辛伐他汀可以显著地抑制TLR4mRNA、IL-6及TNF-α的表达,与辛伐他汀组比较,差异有统计学意义(P<0.01)。结论辛伐他汀对ox-LDL诱导的VSMC炎症因子的表达具有抑制作用,可以通过抑制TLR4的表达,进而抑制ox-LDL-TLR4信号通路而发挥作用。

    Abstract:

    Aim To investigate the effect and mechanism of simvastatin on the expressions of inflammatory factors in cultured rat vascular smooth muscle cells (VSMC) induced by oxidized low density lipoprotein (ox-LDL).Methods The rat VSMC were cultured in vitro.Through pretreatment with anti-TLR4 antibody and simvastatin prior to ox-LDL exposure,the expression of TLR4 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR).The levels of IL-6 and TNF-α in supernatant medium were detected by enzyme linked immunosorbent assay (ELISA).Results Incubation of VSMC with ox-LDL could enhance the expressions of IL-6 and TNF-α.The expressions of IL-6 and TNF-α were attenuated by pretreatment with anti-TLR4 antibody prior to ox-LDL exposure in a concentration-dependent manner (P<0.01).Different concentrations of simvastatin dramatically reduce the expression of TLR4 mRNA (P<0.01),the effect was concentration-dependent,at the same time,the expressions of IL-6 and TNF-α were attenuated by simvastatin in a concentration-dependent manner (P<0.05).Simvastatin dramatically reduced the expressions of TLR4 mRNA,IL-6 and TNF-αby pretreatment with anti-TLR4 antibody prior to ox-LDL exposure compared to the Simvastatin group(P<0.01).Conclusions Simvastatin could reduce the expressions of inflammatory factors in VSMC induced by ox-LDL,the mechanism may be by inhibiting the activation of TLR4 signaling.

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许旭光,张延斌,孔刘莎,王诚.辛伐他汀通过抑制TLR4信号通路调节血管平滑肌细胞炎症因子的表达[J].中国动脉硬化杂志,2014,22(12):1220~1224.

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  • 收稿日期:2014-02-14
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