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 â ), model group (Group â ¡), atorvastatin group (Group â ¢) and FTZ group (Group â £), 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 â ¡, iliac artery restenosis was significantly ameliorated in Group â £ (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 â £ (P < 0.01) than that in Group â ¡. 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.
Subject(s)
Adiponectin/blood , Arterial Occlusive Diseases/drug therapy , Drugs, Chinese Herbal/therapeutic use , Iliac Artery/drug effects , Vascular System Injuries/drug therapy , AMP-Activated Protein Kinases/metabolism , Angioplasty, Balloon , Animals , Arterial Occlusive Diseases/blood , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/pathology , Diet, High-Fat , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , 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/etiology , Vascular System Injuries/pathologyABSTRACT
OBJECTIVE: To establish rabbit model of restenosis after carotid endarterectomy surgery, and to study tissue inflammatory cytokines (TNF-α, IL-6) involved in restenosis. METHODS: A total of 32 rabbits were randomly divided into two groups: model group and control group. The right common carotid artery in rabbits was damaged by carotid endar terectomy in model group. The tissues were harvested at different time points respectively, the pathological changes of the vascular wall after operation were observed at different time points. The changes of expression of tissue vascular wall inflammatory cytokines (TNF-α, IL-6) at different time points after the surgery was observed by RT-PCR, and the changes of serum inflammatory cytokines (TNF-α, IL -6) were detected by ELISA. RESULTS: The new intima appeared after 7 days of the injury and reached the peak on 28 d which is uneven and significantly thicker than the control group (P<0.01). The tissue inflammatory cytokines (TNF-α, IL-6) were significantly increased after the rabbit common carotid artery injury, which was significant difference compared with normal control group (P<0.05). CONCLUSIONS: The tissue inflammatory factors significantly increase after the rabbit carotid artery injury, which suggests the mutual concurrent effects of inflammatory cytokines can result in the proliferation of vascular restenosis.
Subject(s)
Carotid Artery, Common/metabolism , Carotid Artery, Common/surgery , Carotid Stenosis/metabolism , Endarterectomy, Carotid/methods , Interleukin-6/biosynthesis , Tumor Necrosis Factor-alpha/metabolism , Animals , Carotid Artery, Common/chemistry , Interleukin-6/genetics , Interleukin-6/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rabbits , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/geneticsABSTRACT
OBJECTIVE@#To establish rabbit model of restenosis after carotid endarterectomy surgery, and to study tissue inflammatory cytokines (TNF-α, IL-6) involved in restenosis.@*METHODS@#A total of 32 rabbits were randomly divided into two groups: model group and control group. The right common carotid artery in rabbits was damaged by carotid endar terectomy in model group. The tissues were harvested at different time points respectively, the pathological changes of the vascular wall after operation were observed at different time points. The changes of expression of tissue vascular wall inflammatory cytokines (TNF-α, IL-6) at different time points after the surgery was observed by RT-PCR, and the changes of serum inflammatory cytokines (TNF-α, IL -6) were detected by ELISA.@*RESULTS@#The new intima appeared after 7 days of the injury and reached the peak on 28 d which is uneven and significantly thicker than the control group (P<0.01). The tissue inflammatory cytokines (TNF-α, IL-6) were significantly increased after the rabbit common carotid artery injury, which was significant difference compared with normal control group (P<0.05).@*CONCLUSIONS@#The tissue inflammatory factors significantly increase after the rabbit carotid artery injury, which suggests the mutual concurrent effects of inflammatory cytokines can result in the proliferation of vascular restenosis.