Mechanism of tetrahydropalmatine inhibiting oxidative stress damage of VSMCs induced by PDGF-BB
- VernacularTitle:延胡索乙素改善PDGF-BB诱导的VSMCs氧化应激损伤的机制
- Author:
Wenming CHEN
1
;
Minghui JIAN
1
Author Information
1. Dept. of Cardiovascular Medicine,the Affiliated Hospital of Zunyi Medical University,Guizhou Zunyi 563000,China
- Publication Type:Journal Article
- Keywords:
tetrahydropalmatine;
platelet-derived growth
- From:
China Pharmacy
2024;35(15):1855-1861
- CountryChina
- Language:Chinese
-
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.