Effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus on Formation of Atherosclerotic Plaque in ApoE-/- Mice Based on Autophagy of Vascular Smooth Muscle / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus medicine on the proliferation and autophagy levels of aortic plaque vascular smooth muscle cells （VSMCs） in ApoE^-/- mice with atherosclerosis （AS）. Method:A total of 40 ApoE^-/- mice were fed with high-fat diet to replicate AS animal models. They were randomly divided into model group， Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group， and 10 mice with normal diet C57BL/6J mice were the blank group. The blank group and the model groups were given normal saline by gavage， while Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group were given corresponding drugs by gavage for 8 weeks. After the experiment， the mice were sacrificed. Total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） levels were detected by the Microplate reader， the ratio of the aortic plaque area to the total area was observed and measured by staining with aortic gross oil red O. Western blot method was used to detect the proliferation-related protein proliferating cell nuclear antigen （PCNA） and <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA） levels of VSMCs in the aortic media. Transmission electron microscopy was used to observe the autophagosomes of VSMCs and detect the expressions of VSMCs autophagy-related proteins Beclin-1， light chain proteinⅡ （LC3Ⅱ） and p62. Result:Compared with the model group， the Trichosanthis Fructus-Allii Macrostemonis Bulbus group showed significant reduction in the aortic lipid accumulation and plaque area of AS mice and the levels of TC， TG， LDL-C （<italic>P</italic><0.01） and increase of HDL-C （<italic>P</italic><0.05）. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly reduced the levels of proliferation-related antigens PCNA and <italic>α</italic>-SMA in aortic VSMCs （<italic>P</italic><0.01）， and inhibited the excessive proliferation of VSMCs. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly up-regulated Beclin-1 and LC3Ⅱ in aortic VSMCs protein expression， decreased p62 accumulation （<italic>P</italic><0.01）， increased the expressions of VSMCs autophagosomes， and increased the autophagy level of VSMCs. Conclusion:Trichosanthis Fructus-Allii Macrostemonis Bulbus regulates blood lipid levels in AS mice， and inhibits the excessive proliferation of aortic VSMCs and plaque formation in the aorta of AS mice. The mechanism may be related to the up-regulation of the autophagy activity of VSMCs.