| BACKGROUND:In recent years,with the rapid improvement of percutaneous coronary intervention,especially the development of second-generation drug-eluting stent(DES)technology,incidence of restenosis has decreased to 10-15%.However,the residual metal stent impairs the recovery of vascular function,leading to late stent thrombosis,which limits the long-term development of DES.The latest clinical studies show that compared with the second-generation DES,the polymer-absorbable stent not only causes a higher rate of restenosis,but also significantly increases the risk of serious cardiac adverse events such as previous stent thrombosis;and it’s reported that biomarkers of metal-absorbable stents exist hidden danger of causing non-Q-wave myocardial infarction.Therefore,effective prevention and treatment of restenosis after angioplasty remains a worldwide problem.Fufang-Zhenzhu-Tiaozhi Capsule(FTZ),a traditional Chinese medicine researched and developed by Guangdong Pharmaceutical University,has obvious effects on the treatment for dyslipidemia and atherosclerosis.With the properties of protecting the vascular endothelium function and inhibiting inflammation,FTZ is a promising drug to be applied in therapy of cardiovascular disease.Our previous study found that FTZ can reduce the degree of vascular restenosis,but its concrete mechanism remains to be elucidated.OBJECTIVE:To observe the effect of FTZ on prevention and treatment of rabbit iliac artery restenosis after angioplasty,and to explore its possible mechanism.METHODS:Male New Zealand white rabbits(body weight: 2.0±0.2 Kg)were randomly divided into sham operation group,model group,atorvastatin group and FTZ group,with 10 rabbits in each group.Blood sample was taken to test lipids before the operation.Heart rate,blood pressure and electrocardiogram monitoring was continued during the operation.Except for the sham operation group,the experimental animals in the other groups underwent percutaneous iliac artery transluminal balloon angioplasty and fed with high-fat diet.Four weeks later,blood sample was taken to test blood biochemical index,echocardiography and angiography were performed.The model group and the drug-treated group underwent percutaneous balloon angioplasty again on target vessel.All were fed with normal diet for 4 weeks,and at the same time,the drug-treated group was given either atorvastatin or FTZ by nasal feeding.Finally,blood sample was taken to measure blood biochemical index,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);cardiac echocardiography and angiography were reviewed;and injured iliac artery was collected for hematoxylin-eosin(HE)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).RESULTS:At the beginning,in four groups there was no significant difference in body mass and blood lipids,including triglyceride(TRIG),total cholesterol(CHOL),high-density lipoprotein cholesterol(HDL-c),low-density lipoprotein cholesterol(LDL-c)as well as very low-density lipoprotein cholesterol(VLDL-c)(P>0.05).Moreover,both the ratio of the degree of stenosis to the reference diameter of the vessel lumen(MLD %)and the ratio of the lesion area to the vascular cavity reference area(MLA %)of the iliac artery angiography in four groups were of no statistical difference(P>0.05).Before and after taking the drugs,compared with the sham operation group,the body mass of the other there groups was significantly increased(P<0.05),but there was no significant difference between the other groups(P>0.05).What’s more,TRIG,liver and kidney function indicators,creatine kinase,as well as measurement of echocardiography were of no statistical difference in four groups(P>0.05).At the 4th week of the experiment,the level of CHOL,HDL-c,LDL-c,and VLDL-c,and iliac artery angiography results MLD%,along with MLA% were significantly higher in the other three groups than in the sham operation group(P<0.01).However,iliac artery MLD% and MLA% were significantly decreased after percutaneous balloon angioplasty on target vessel in the model group and the drug-treated group(P<0.05).At the 8th week of the experiment,compared with the sham operation group,the level of CHOL,HDL-c,LDL-c,VLDL-c,IL-6,TNF-α,and MCP-6,and iliac artery angiography results MLD%,along with MLA% in the model group were significantly increased(P<0.01),while the level of APN was decreased significantly(P<0.01).Compared with the model group,the level of CHOL,HDL-c,LDL-c,VLDL-c,IL-6,TNF-α,and MCP-6,and iliac artery angiography results MLD%,along with MLA% were significantly decreased in the drug-treated group(P< 0.01),while the level of APN was significantly elevated(P<0.01).As for HE staining of injured iliac artery,compared with the sham operation group,different degrees of intima hyperplasia was observed in the other three groups,and a large number of smooth muscle cells as well as foam cells was seen in the media layer of the model group.Compared with the model group,intimal hyperplasia was alleviated in the drug-treated group;moreover,both smooth muscle cells and foam cells were significantly reduced in the media layer.Western blotting detection of the injured iliac artery showed that the expressions of PPAR-α,AMPK and p-AMPK in the other three groups were up-regulated compared with the sham operation group(P<0.01).Compared with the model group,the expression of AMPK was significantly increased in the drug-treated group(P<0.01),but the expression of PPAR-α and p-AMPK was significantly increased only in the FTZ group(P<0.01).CONCLUSION:FTZ can reduce blood lipid levels and inhibit rabbit’s iliac artery restenosis after angioplasty effectively and safely,and its mechanism may be related to activation of APN signaling pathway. |
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