| BACKGROUND: Coronary heart disease has become a major disease that threatening human health,unfortunately,the incidence and mortality of the disease increasing.Percutaneous coronary intervention(PCI)is a common treatment for coronary heart disease.However,the high incidence of restenosis after PCI is still an important medical problem.Conventional clinical application of antithrombotic,anticoagulant,blood lipid-regulating drugs,angiotensin II receptor antagonist(ARB),angiotensin converting enzyme inhibitor(ACEI)and other drugs failed to achieve a good effect of restenosis after PCI.With the rapid development and continuous improvement of PCI,the emergence of bare metal stents and drug eluting stents,especially the development of second generation drug eluting stents,has reduced the incidence of restenosis after PCI.However,the permanent metal stent body remnants could affect the repair of blood vessel function,and various studies have shown that drug-eluting stents can easily lead to the formation of late thrombosis,which greatly limits the long-term efficacy of drug-eluting stents.Based on this,bio-absorbable stents came into being.However,the latest research shows that the bio-absorbable stents not only cause higher late restenosis rate,but also increase the risk of serious adverse cardiac events such as early stent thrombosis significantly,and high medical expenses also caused a serious economic burden on the families and society.Therefore,the current drugs and methods for the treatment and prevention of restenosis have great limitations.whether it is possible to find a drug that can effectively prevent and treat vascular restenosis has become an urgent task to be solved in the domestic and foreign research fields.The mechanism of restenosis after PCI is very complicated.It mainly involves elastic retraction after vascular dilation,impaired function of vascular endothelial cells leads to inflammatory reactions,sub-acute thrombosis,and migration and proliferation of sub-endothelial vascular smooth muscle cells to the media of the vascular membrane and Increase in extracellular matrix production.After balloon inflation or stent implantation during PCI,the destruction and exfoliation of the vascular endothelial cells can cause a series of inflammatory cascades such as the release of inflammatory mediators and chemokine.In turn,chronic inflammation continues to act on the vessel wall causing stenosis of the lumen.It is considered that inflammatory reaction is the initiating factor for the development of restenosis after PCI.How to effectively inhibit the inflammatory reaction is the key to prevent restenosis.Nuclear factor-κB(NF-κB)is a major inflammatory response transcription factor.A large number of studies have concluded that the activation of NF-κB plays an important role in the inflammatory response to restenosis after angioplasty.In addition to the inflammatory reaction itself,NF-κB also affects the structural and functional repair after vascular endothelial injury.Activation of the NF-κB pathway is involved in the development of vascular restenosis,and inhibition of NF-κB activation may be one of the therapeutic targets for reducing the incidence of restenosisFufang Zhenzhu Tiaozhi capsule(FTZ)could comprehensively regulate the body’s lipid metabolism disorders and treat the hyperlipidemia and lipid metabolism related diseases through a variety of ways and targets.In previous clinical practice and experimental studies,it was found that FTZ significantly reduced total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and elevation the high-density lipoprotein cholesterol(HDL-C)and play a role in the prevention and treatment of atherosclerosis.Not only that,FTZ also has the role of protecting the vascular endothelium and inhibiting the inflammatory response,and has a good application prospect in the prevention and treatment of cardiovascular diseases.Therefore,it is of great scientific significance and clinical value to further study the effect and mechanism of FTZ in preventing and treating vascular restenosis.Aim: A restenosis model was established by percutaneously puncturing the iliac artery after balloon injury to the abdominal aorta,following high fat foods.This study explored the effect of FTZ on blood lipid level and inflammatory factors based on the model of abdominal aorta restenosis after balloon injuries in rabbits,make it clear whether FTZ plays a role in the prevention and treatment of restenosis by lowering serum lipid levels,regulating NF-κB pathway and inhibiting the production of various inflammatory factors.METHODS: Forty New Zealand white rabbits were randomly divided into five groups(n=8)after one week of feeding.They were blank control group,restenosis model group,FTZ group,atorvastatin group,FTZ and atorvastatin mixed group.Apart from the sham operation in the control group,the remaining groups were made restenosis models of abdominal aortic endothelial vascular injury.After 4 weeks of high-fat diet,the model group and the drug groups were subjected to balloon dilatation to create a restenosis model.The angiographic results were analyzed with a two-dimensional quantitative angiography workstation.The ratio of the degree of stenosis to the reference diameter of the vessel lumen(%MLD),the ratio of the lesion area to the vascular cavity reference area(%MLA)was calculated for each experimental group.Blood drawn to determine serum lipid levels: serum total cholesterol(TC),triglyceride concentration(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),very low-density lipoprotein cholesterol(VLDL-C)and serum cytokine concentrations.Oil red staining was used to observe the formation of abdominal aortic atherosclerotic plaques.Hematoxylin-eosin staining was used to observe the intimal hyperplasia,endothelial thickness(IT)and intima/media thickness(IMRS)were measured.Immunohistochemical staining and western blotting were performed to observe the expression of NF-κB in the injured area.RESULTS: Percutaneous balloon injury of the abdominal aorta combined with a high-fat diet could successfully establish a vascular restenosis model after balloon angioplasty.Compared with the control group,oil red staining showed a large number of lipid plaques in the stenosis of the model group,and angiography confirmed that the MLD% and MLA% in the model group increased significantly(P<0.01).HE staining showed that the intimal thickness and intima/media in the restenosis model group were significantly higher(P<0.01).It was suggested that there was a significant intimal hyperplasia after balloon injury.The model of restenosis after balloon injury was successfully made.Compared with the blank control group,the levels of blood lipids and inflammatory factors in the restenosis model group were significantly higher(P < 0.01).Immunohistochemical staining and western blotting showed that the expression of NF-κB in the model group increased significantly(P <0.01).It indicates that there is obvious dyslipidemia and significant inflammatory reaction during the establishment of the model.Compared with the model group,the blood lipid levels and inflammatory factor concentrations in the FTZ group were significantly decreased(P < 0.05),indicating that FTZ can regulate dyslipidemia and reduce inflammation,the intimal thickness,intima-media ratio,and MLD% and MLA% in the angiographic results were significantly decreased(P < 0.05),indicating that FTZ can inhibit intimal hyperplasia.Immunohistochemistry and western blotting showed that the expression of NF-κB in the FTZ group was significantly lower than that in the restenosis model group(P < 0.05),indicating that FTZ reduced the expression of NF-κB in the tissue.Compared with the FTZ group,there was no significant difference in blood lipid levels,inflammatory factor concentration levels,intimal thickness,intima-media ratio,MLD% and MLA% angiography results,and NF-κB blood vessel expression levels in the atorvastatin group(P >0.05),it shows that the strength of the two drugs treatment of restenosis is quite similar.Compared with single drug group,the concentration of TC,LDL,and VLDL was decreased(P< 0.05),the expression of some cytokines was decreased,and the expression of NF-κB was decreased in immunohistochemistry(P <0.05)in mixed drug group,it showed that the combination therapy has more significant effect on the restenosis than the single drug.Conclusion: Abdominal artery balloon injuries and high fat diets could successfully induce restenosis.The results suggest FTZ could inhibit restenosis via reducing NF-kappaB activity and inflammatory factor expression within the atherosclerotic lesion. |
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