CHEN Wenming,JIAN Minghui.Mechanism of tetrahydropalmatine inhibiting oxidative stress damage of VSMCs induced by PDGF-BB[J].ZHONGGUO YAOFANG,2024,35(15):1855-1861.
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
2
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
2
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
2
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.
REMPAKOS A,KOSTANTINIS S,SIMSEK B,et al. Update on chronic total occlusion percutaneous coronary intervention[J]. J Invasive Cardiol,2023,35(4):E194-E204.
TAO S Y,TANG X W,YU L T,et al. Prognosis of coronary heart disease after percutaneous coronary intervention:a bibliometric analysis over the period 2004-2022[J]. Eur J Med Res,2023,28(1):311.
PELLICCIA F,ZIMARINO M,NICCOLI G,et al. In-stent restenosis after percutaneous coronary intervention:emerging knowledge on biological pathways[J]. Eur Heart J Open,2023,3(5):oead083.
DU Q Y,MENG X L,WANG S H. A comprehensive review on the chemical properties,plant sources,pharmacological activities,pharmacokinetic and toxicological cha- racteristics of tetrahydropalmatine[J]. Front Pharmacol,2022,13:890078.
JIAN M H,CHEN W M,ZHANG Y. Inhibitory effect of tetrahydropalmatine on apoptosis and oxidative stress of H9c2 cells induced by high glucose[J]. J Zunyi Med Univ,2022,45(3):317-321.
MCCORD J M,GAO B F,HYBERTSON B M. The complex genetic and epigenetic regulation of the Nrf2 pathways:a review[J]. Antioxidants (Basel),2023,12(2):366.
SI J Y,MENG R R,GAO P,et al. Linagliptin protects rat carotid artery from balloon injury and activates the Nrf2 antioxidant pathway[J]. Exp Anim,2019,68(1):81-90.
QIU Z M,CHEN W M,WANG Y,et al. Effect of ginseno-side Rg3 on apoptosis and expression of apoptosis related genes of vascular smooth muscle cells in rats[J]. J Zunyi Med Univ,2020,43(4):419-424.
LI Y,AN Y,ZHANG H B,et al. Effects of jaranol on proliferation and migration of vascular smooth muscle cells induced by PDGF-BB[J]. Chin J Arterioscler,2023,31(10):865-871.
YIN X Z,LI W B,ZHANG J X,et al. AMPK-mediated metabolic switching is high effective for phytochemical levo-tetrahydropalmatine (l-THP) to reduce hepatocellular carcinoma tumor growth[J]. Metabolites,2021,11(12):811.
TANG H Y,CHEN A Q,ZHANG H,et al. Vascular smooth muscle cells phenotypic switching in cardiovascular diseases[J]. Cells,2022,11(24):4060.
QIU L Q,HU L L,LIU X X,et al. Physalin B inhibits PDGF-BB-induced VSMC proliferation,migration and phenotypic transformation by activating the Nrf2 pathway[J]. Food Funct,2021,12(21):10950-10966.
KIM N,HWANGBO C,LEE S,et al. Eupatolide inhibits PDGF-induced proliferation and migration of aortic smooth muscle cells through ROS-dependent heme oxygenase-1 induction[J]. Phytother Res,2013,27(11):1700-1707.
ZHANG J,CAI W Y,FAN Z X,et al. MicroRNA-24 inhibits the oxidative stress induced by vascular injury by activating the Nrf2/HO-1 signaling pathway[J]. Atherosclerosis,2019,290:9-18.
ZHANG C C,KONG X H,MA D L.MiR-141-3p inhibits vascular smooth muscle cell proliferation and migration via regulating Keap1/Nrf2/HO-1 pathway[J]. IUBMB Life,2020,72(10):2167-2179.