Lacidipine Ameliorates the Endothelial Senescence and Inflammatory Injury Through CXCR7/P38/C/EBP-β Signaling Pathway.
Lacidipine Ameliorates the Endothelial Senescence and Inflammatory Injury Through CXCR7/P38/C/EBP-β Signaling Pathway.
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DOI：
10.3389/fcvm.2021.692540
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发表时间：
2021
影响因子：
3.6
通讯作者：
Xu S
中科院分区：
文献类型：
--
作者：
Liu X;Huang Z;Zhang Y;Shui X;Liu F;Wu Z;Xu S
背景资料：拉西地平是第三代钙通道阻滞剂，除降压外，对高血压患者的内皮细胞也有保护作用。然而，拉西地平相关的内皮保护的详细机制仍然是难以捉摸的。研究方法：将16只自发性高血压大鼠（SHR）随机分为拉西地平治疗组和生理盐水对照组。连续四周监测尾部收缩压。内皮细胞（ECs）在体外用H2 O2、博莱霉素或脂多糖（LPS）刺激前用拉西地平预处理。然后，分别通过Cell Counting Kit-8测定、transwell测定和β-半乳糖苷酶染色来测量细胞活性、迁移和衰老。以2′，7′-二氯荧光素二乙酸酯（DCFH-DA）为荧光探针，检测细胞内活性氧（ROS）水平。Western blotting和免疫荧光检测相关蛋白表达。结果如下：结果显示，拉西地平可降低SHR的血压，同时上调CXCR 7的表达，抑制P38和CCAAT/增强子结合蛋白β（C/EBP-β）的表达。体外实验进一步证明拉西地平通过CXCR 7/P38/信号通路增加了在氧化应激、细胞衰老和炎症活化下的EC的细胞活力和功能。结论：提示拉西地平通过调节CXCR 7/P38/C/EBP-β信号通路对EC衰老、氧化应激和炎症损伤具有保护作用。
Background: Lacidipine, a third-generation calcium channel blocker, exerts beneficial effects on the endothelium of hypertensive patients in addition to blood pressure lowering. However, the detailed mechanism underlying Lacidipine-related endothelial protection is still elusive. Methods: Sixteen spontaneous hypertensive rats (SHRs) were randomly divided into two groups: Lacidipine-treated SHR group and saline-treated control group. Tail systolic blood pressure was monitored for four consecutive weeks. Endothelial cells (ECs) were pretreated with Lacidipine prior to being stimulated with H2O2, bleomycin, or Lipopolysaccharides (LPS) in vitro. Then, cell activity, migration, and senescence were measured by Cell Counting Kit-8 assay, transwell assay, and β-galactosidase staining, respectively. The fluorescent probe 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) was used to assess the intracellular reactive oxygen species (ROS). Related protein expression was detected by Western blotting and immunofluorescence. Results: Our data showed that Lacidipine treatment lowered the blood pressure of SHRs accompanied by the elevation of CXCR7 expression and suppression of P38 and CCAAT/enhancer-binding protein beta (C/EBP-β) compared with the control group. In vitro experiments further demonstrated that Lacidipine increased the cell viability and function of ECs under oxidative stress, cell senescence, and inflammatory activation via the CXCR7/P38/signaling pathway. Conclusions: Our results suggested that Lacidipine plays a protective role in EC senescence, oxidative stress, and inflammatory injury through the regulation of CXCR7/P38/C/EBP-β signaling pathway.