Mechanism of tetrahydropalmatine inhibiting oxidative stress damage of VSMCs induced by PDGF-BB
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.
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