Fufang-Zhenzhu-Tiaozhi capsule ameliorates rabbit's iliac artery restenosis by regulating adiponectin signaling pathway

Biomed Pharmacother. 2020 Aug:128:110311. doi: 10.1016/j.biopha.2020.110311. Epub 2020 Jun 2.

Abstract

Background and purpose: Fufang-Zhenzhu-Tiaozhi Capsule (FTZ), a traditional Chinese medicine, has been shown obvious effects on the treatment of dyslipidemia and atherosclerosis. The aim of this study was to evaluate whether FTZ can ameliorate rabbit iliac artery restenosis after angioplasty by regulating adiponectin signaling pathway.

Experimental approach: The rabbit iliac artery restenosis model was established through percutaneous iliac artery transluminal balloon angioplasty and a high-fat diet. Twenty eight male New Zealand rabbits (8-week-old) were divided into sham operation group (Group Ⅰ), model group (Group Ⅱ), atorvastatin group (Group Ⅲ) and FTZ group (Group Ⅳ), with 7 rabbits in each group. Vascular stenosis was analyzed with Digital Subtraction Angiography. Level of adiponectin (APN), and inflammatory factor including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) as well as monocyte chemoattractant protein-1 (MCP-1) was measured by Enzyme Linked Immunosorbent Assay; and injured iliac artery was collected for Hematoxylin-eosin staining and Western Blotting detection of expression of peroxisome proliferator-activated receptor-alpha (PPAR-α), adenosine 5'-monophosphate -activated protein kinase (AMPK) and phosphorylated adenosine 5'-monophosphate -activated protein kinase (p-AMPK). Besides, we evaluated FTZ's safety for the first time.

Key results: Percutaneous iliac artery transluminal balloon angioplasty and high-fat diet result in inflammatory response and restenosis. Compared with Group Ⅱ, iliac artery restenosis was significantly ameliorated in Group Ⅳ (P < 0.05). Treated with FTZ, serum lipids were significantly decreased (P < 0.01), while the level of APN was elevated significantly (P < 0.01). Western blotting detection of the injured iliac artery showed that the expressions of PPAR-α, AMPK and p-AMPK were significantly increased in Group Ⅳ (P < 0.01) than that in Group Ⅱ. Besides, before and after taking drugs, liver and kidney function indicators, creatine kinase, as well as measurement of echocardiography were of no statistical difference in four groups(P > 0.05).

Conclusions and implications: FTZ could effectively reduce serum lipids and ameliorate rabbit's iliac artery restenosis after angioplasty, and its mechanism may be related to activation of APN signaling pathway.

Keywords: Adiponectin signal pathway; FTZ; Lipid; Restenosis after angioplasty.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adiponectin / blood*
  • Angioplasty, Balloon
  • Animals
  • Arterial Occlusive Diseases / blood
  • Arterial Occlusive Diseases / drug therapy*
  • Arterial Occlusive Diseases / etiology
  • Arterial Occlusive Diseases / pathology
  • Diet, High-Fat
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Iliac Artery / drug effects*
  • Iliac Artery / injuries
  • Iliac Artery / metabolism
  • Iliac Artery / pathology
  • Inflammation Mediators / blood
  • Male
  • PPAR alpha / metabolism
  • Phosphorylation
  • Rabbits
  • Recurrence
  • Signal Transduction
  • Vascular System Injuries / blood
  • Vascular System Injuries / drug therapy*
  • Vascular System Injuries / etiology
  • Vascular System Injuries / pathology

Substances

  • Adiponectin
  • Drugs, Chinese Herbal
  • Inflammation Mediators
  • PPAR alpha
  • zhenshu tiaozhi formula
  • AMP-Activated Protein Kinases