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延胡索乙素改善PDGF-BB诱导的VSMCs氧化应激损伤的机制
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| 篇名： | 延胡索乙素改善PDGF-BB诱导的VSMCs氧化应激损伤的机制 |
| TITLE： | Mechanism of tetrahydropalmatine inhibiting oxidative stress damage of VSMCs induced by PDGF-BB |
| 摘要： | 目的 研究延胡索乙素（Thp）对血小板衍生生长因子-BB（PDGF-BB）诱导的大鼠主动脉血管平滑肌细胞（VSMCs）氧化应激损伤的保护作用，并基于核因子红系2相关因子2（Nrf2）/血红素加氧酶1（HO-1）信号通路探究其可能机制。方法在Thp抑制PDGF-BB诱导的VSMCs氧化应激损伤效应研究中，将VSMCs分为对照组、PDGF-BB组（25ng/mL）及Thp低、中、高浓度组（5、10、20mg/mL）。在Thp作用机制研究（沉默Nrf2）中，将VSMCs分为PDGF-BB+阴性对照siRNA（NC-siNrf2）组（25ng/mLPDGF-BB+NC-siNrf2），PDGF-BB+Thp+NC-siNrf2组（25ng/mLPDGF-BB+10mg/mLThp+NC-siNrf2），PDGF-BB+Nrf2小干扰RNA（siNrf2）组（25ng/mLPDGF-BB+siNrf2），PDGF-BB+Thp+siNrf2组（25ng/mLPDGF-BB+10.0mg/mLThp+siNrf2）。2个实验均检测VSMCs的增殖、迁移能力，活性氧（ROS）水平，超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以及Nrf2和HO-1蛋白表达。结果与对照组比较，PDGF-BB组VSMCs的增殖、迁移能力显著增强（P＜0.01），ROS水平显著升高（P＜0.01），SOD、CAT活性及Nrf2、HO-1蛋白的相对表达量均显著降低（P＜0.01）；与PDGF-BB组比较，Thp不同浓度组VSMCs的增殖、迁移能力均显著下降（P＜0.01），ROS水平均显著降低（P＜0.01），SOD、CAT活性及Nrf2、HO-1蛋白的相对表达量均显著升高（P＜0.01）。沉默Nrf2可显著逆转Thp对PDGF-BB诱导VSMCs氧化应激损伤的改善作用（P＜0.01）。结论Thp可以通过激活Nrf2介导的抗氧化防御途径来降低VSMCs的氧化应激水平，从而抑制VSMCs的增殖、迁移。 |
| ABSTRACT： | OBJECTIVE To study the protective effect of tetrahydropalmatine （Thp） on platelet-derived growth factor-BB （PDGF-BB） induced oxidative stress injury in vascular smooth muscle cells （VSMCs） of rats， and to explore its possible mechanism based on the nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase （HO-1） signaling pathway. METHODS In the study about Thp inhibiting PDGF-BB-induced oxidative stress injury in VSMCs， VSMCs were divided into control group， PDGF-BB group （25 ng/mL）， and Thp low-concentration， medium-concentration and high-concentration groups （5， 10， 20 mg/mL）. In the Thp mechanism experiment （silencing Nrf2）， VSMCs were divided into PDGF-BB+negative control of siRNA （NC-siNrf2） group （25 ng/mL PDGF-BB+NC-siNrf2）， PDGF-BB+Thp+NC-siNrf2 group （25 ng/mL PDGF-BB+10 mg/mL Thp+NC-siNrf2）， PDGF-BB+Nrf2 small interfering RNA （siNrf2） group （25 ng/mL PDGF-BB+siNrf2） and PDGF-BB+Thp+siNrf2 group （25 ng/mL PDGF-BB+10.0 mg/mL Thp+siNrf2）. The proliferative and migratory capabilities of VSMCs， the level of reactive oxygen species （ROS）， the activities of superoxide dismutase （SOD） and catalase （CAT） as well as the protein expressions of Nrf2 and HO-1 in VSMCs were all detected in two experiments. RESULTS Compared with the control group， the proliferative and migratory capabilities of VSMCs in the PDGF-BB group were significantly enhanced （P＜0.01）， and the level of ROS significantly increased （P＜0.01）， while the activities of SOD and CAT， and the relative expressions of Nrf2 and HO-1 protein significantly decreased （P＜0.01）. Compared with the PDGF-BB group， the proliferative and migratory capabilities of VSMCs in the Thp groups at different concentrations were significantly reduced （P＜0.01）， the levels of ROS were significantly reduced， while the activities of SOD and CAT， and relative expressions of Nrf2 and HO-1 were significantly enhanced （P＜0.01）. Silencing Nrf2 significantly reversed the improvement of Thp on the oxidative stress damage of VSMCs induced by PDGF-BB （P＜0.01）. CONCLUSIONS Thp can reduce the oxidative stress level of VSMCs by activating the Nrf2-mediated antioxidant defense pathway， thereby inhibiting the proliferation and migration of VSMCs. |
| 期刊： | 2024年第35卷第15期 |
| 作者： | 陈文明；蹇明辉 |
| AUTHORS： | CHEN Wenming，JIAN Minghui |
| 关键字： | 延胡索乙素；血小板衍生生长因子-BB；血管平滑肌细胞；Nrf2/HO-1信号通路；氧化应激 |
| KEYWORDS： | tetrahydropalmatine； platelet-derived growth |
| 阅读数： | 1 次 |
| 本月下载数： | 0 次 |
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