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番茄红素调节RAS同源基因家族成员A/Rho相关激酶信号通路对氧化低密度脂蛋白诱导脑血管内皮细胞凋亡的影响

Effect of lycopene on oxidized low-density lipoprotein induced apoptosis of cerebral vascular endothelial cells by regulating the RAS homologous gene family member A/Rho-related kinase signaling pathway

    摘要
  • 摘要:
    目的 探讨番茄红素（LYC）调节RAS同源基因家族成员A（RhoA）/Rho相关激酶（ROCK）信号通路对氧化低密度脂蛋白（ox-LDL）诱导的脑血管内皮细胞（EC）凋亡的影响。
    方法 未做任何处理的人脑微血管内皮细胞（HBMECs）设为NC组；采用ox-LDL处理的HBMECs分为ox-LDL组、LYC组（0.5 μmol/L的LYC处理HBMECs）、溶血磷脂酸（LPA）组（5 μmol/L RhoA/ROCK信号通路激活剂LPA处理HBMECs）、LYC+LPA组（0.5 μmol/L的LYC以及5 μmol/L LPA共同处理HBMECs）；处理24 h后用于后续实验。采用酶联免疫吸附试验（ELISA）检测HBMECs细胞因子水平；CCK-8法检测HBMECs增殖；流式细胞术检测HBMECs凋亡率；Western blot检测细胞血小板内皮细胞黏附分子-1（CD31）、平滑肌（SM）22α、BCL-2相关X蛋白（Bax）、B细胞淋巴瘤/白血病-2蛋白（Bcl-2）、裂解的半胱氨酸天冬氨酸蛋白酶3（cleaved-Caspase-3）、RhoA/ROCK通路相关蛋白表达。
    结果 与NC组相比，ox-LDL组单核细胞趋化蛋白1（MCP-1）、白细胞介素（IL）-6、血管内皮细胞黏附分子1（VCAM-1）、HBMECs凋亡率、Bax、cleaved-Caspase-3、SM22α、RhoA、ROCK1蛋白水平升高，OD值、Bcl-2、CD31蛋白水平下降，差异有统计学意义（P < 0.05）；与ox-LDL组相比，LYC组MCP-1、IL-6、VCAM-1、HBMECs凋亡率、Bax、cleaved-Caspase-3、SM22α、RhoA、ROCK1蛋白水平降低，OD值、Bcl-2、CD31蛋白水平升高，差异有统计学意义（P < 0.05），而LPA组趋势相反；LPA减弱了LYC对ox-LDL诱导的HBMECs凋亡的改善作用。
    结论 LYC可能通过抑制RhoA/ROCK信号通路来减轻HBMECs凋亡。

     

    Abstract:
    Objective To investigate the effect of lycopene (LYC) on the oxidized low-density lipoprotein (ox-LDL) induced apoptosis of cerebral vascular endothelial cells (EC) by regulating the RAS homologous gene family member A (RhoA)/Rho-related kinase (ROCK) signaling pathway.
    Methods Human brain microvascular endothelial cells (HBMECs) without any treatments were designed as NC group; the HBMECs treated with ox-LDL were divided into ox-LDL group, LYC group (HBMECs treated with 0.5 μmol/L LYC), lysophosphatidic acid (LPA) group (HBMECs treated with 5 μmol/L RhoA/ROCK signaling pathway activator LPA), and LYC+LPA group (HBMECs treated with 0.5 μmol/L LYC and 5 μmol/L LPA); after 24 hours of treatment, they were used for subsequent experiments. Enzyme-linked immunosorbent assay (ELISA) was used to detect the cytokine levels of HBMECs; CCK-8 method was used to detect the proliferation of HBMECs; flow cytometry was used to detect the apoptosis rate of HBMECs; the Western blot was used to detect the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), smooth muscle (SM) 22α, BCL-2 associated X protein (Bax), B-cell lymphoma/leukemia 2 protein (Bcl-2), cleaved-Caspase-3, and RhoA/ROCK pathway related proteins.
    Results Compared with the NC group, the levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), vascular endothelial cell adhesion molecule-1 (VCAM-1), apoptosis rate of HBMECs, the Bax, cleaved-Caspase-3, SM22α, RhoA and ROCK1 proteins in the ox-LDL group increased significantly, while the OD value and the levels of Bcl-2 and CD31 proteins decreased significantly (P < 0.05); compared with the ox-LDL group, the levels of MCP-1, IL-6, VCAM-1, apoptosis rate of HBMECs, the Bax, cleaved-Caspase-3, SM22α, RhoA, and ROCK1 proteins in the LYC group decreased significantly, while the OD value and the levels of Bcl-2 and CD31 proteins increased significantly (P < 0.05), but the trends in the LPA group were opposite; LPA weakened the improvement effect of LYC on apoptosis of HBMECs induced by ox-LDL.
    Conclusion LYC may reduce apoptosis of HBMECs by inhibiting the RhoA/ROCK signaling pathway.

     

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