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TMP-PF降低ApoE-/-小鼠血脂、延缓AS进展
TMP-PF抑制ApoE-/-小鼠斑块血管新生
图2 TMP-PF抑制ApoE-/-小鼠斑块血管新生和血管新生相关因子
与对照组比,模型组TC、TG、LDL-C水平升高,HDL-C水平降低、斑块面积增大(P<0.05,图3A-F);给药后TG、LDL-C水平显著降低、斑块面积减少(P<0.05,图3B、C、E、F),而NR4A1激动剂(CsnB)可逆转药物作用(P<0.05,图3B、C、E、F),提示TMP-PF可能通过抑制NR4A1表达降低血脂、延缓AS进展。
图3 TMP-PF通过抑制ApoE-/-小鼠NR4A1表达而改善AS
TMP-PF通过NR4A1/VEGFR2通路抑制斑块血管新生
图4 TMP-PF通过抑制主动脉NR4A1/VEGFR2通路抑制ApoE-/-小鼠斑块血管新生
TMP-PF对ApoE-/-小鼠心肌组织学和心肌血管新生无明显副作用
Tetramethylpyrazine and paeoniflorin combination (TMP-PF) alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway
Rong Yuana,b, Qiqi Xina,b, Weili Shia,b, Yu Miaoa,b, Zhengchuan Zhub, Yahui Yuana,b, Ying Chenc, Xiaoning Chend, Sean Xiao Lenge,*, Keji Chena,b,*, Weihong Conga,b,*
a Cardiovascular Diseases Laboratory, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
b National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
c School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing 210023, China
d Department of Otolaryngology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
e Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore 21224, United States
*Corresponding author.
Abstract
Atherosclerosis remains a great threat to human health worldwide. Previous studies found that tetramethylpyrazine (TMP) and paeonif lorin (PF) combination (TMP-PF) exerts anti-atherosclerotic effects in vitro. However, whether TMP-PF improves atherosclerosis in vivo needs further exploration. The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE-/- mice and explore the related molecule mechanisms. Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels, suppressed vascular endothelial growth factor receptor 2 (VEGFR2) and nuclear receptor subfamily 4 group A member 1 (NR4A1) expression in aortic tissues, inhibited plaque angiogenesis, reduced plaque areas, and alleviated atherosclerosis in ApoE-/- mice. Also, TMP-PF exhibited a better modulation effect than TMP or PF alone. However, NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF. In conclusion, TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway, indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.
Reference:
YUAN R, XIN Q Q, SHI W L, et al. Tetramethylpyrazine and paeoniflorin combination (TMP-PF) alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway[J]. Food Science and Human Wellness, 2024, 13(5): 2642-2652. DOI:10.26599/FSHW.2022.9250212.
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