丹蒌片预防兔动脉粥样硬化支架置入术后再狭窄的作用及机制研究
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摘要
目的观察丹蒌片对兔动脉粥样硬化金属裸支架置入术后再狭窄的作用及可能机制。方法30只日本大耳白兔术前3天予阿司匹林肠溶片25 mg/d,行球囊损伤加高脂喂养制备兔腹主动脉粥样硬化,4周后动脉造影显示共24只腹主动脉狭窄>30%,病变处置入金属裸支架后随机分为常规治疗组、丹蒌片组、空白对照组3组,每组8只。常规治疗组:给予阿司匹林肠溶片[50 mg/(kg·d)]、氯吡格雷片[25 mg/(kg·d)]和瑞舒伐他汀钙片[1 mg/(kg·d)]灌胃,丹蒌片组:在常规治疗的基础上加丹蒌片[0.5g/(kg·d)]灌胃,空白对照组予以等剂量生理盐水灌胃;均连续灌胃4周。4周后行光学相干断层成像(OCT)检查,血脂、炎症因子指标的检测。处死动物后取材行HE染色、Western blot检测p-AKT蛋白表达。结果 PCI术后4周,常规治疗组和丹蒌片组与本组术前及空白对照组同期比较TG、TC、LDL-C、Hs-CRP及TNF-α均显著降低(均P<0.01),丹蒌片组与常规治疗组比较TC水平降低(P<0.05)。OCT和HE染色分析显示常规治疗组和丹蒌片组与空白对照组比较,内膜增生均匀对称、新生内膜的过度增生和管腔狭窄程度减轻(均P<0.01);丹蒌片组的作用优于常规治疗组,但两组差异无统计学意义(P>0.05)。Western blot显示与空白对照组比较,常规治疗组和丹蒌片组p-AKT蛋白表达均显著性降低(均P<0.01),丹蒌片组与常规治疗组比较,差异无统计学意义(P>0.05)。结论丹蒌片预防兔腹主动脉粥样硬化金属裸置入后的支架内再狭窄,可能与降低炎症反应、通过AKT信号通路而发挥作用。
Objective To observe roles and posible mechanism of Danlou Pill(DLP) for preventing bare metal stent(BMS) in-stent restenosis(ISR) of atherosclerosis rabbits,and to study potential mechanisms.Methods Abdominal aorta atherosclerosis model was established in 30 Japanese big ear rabbits by balloon injury and high-fat diet feeding after they took aspirin(25 mg/d) for 3 days.Four weeks later arteriography showed abdominal aorta atherosclerosis>30% occurred in 24 rabbits.After implanting bare metal stents,the rabbits were randomly divided into 3 groups,the blank control group,the conventional treatment group,and the DLP group,8 in each group.Rabbits in the conventional treatment group were administered with aspirin [50 mg/(kg·d),clopidogrel [25 mg/(kg·d) ],and rosuvastain [1 mg/(kg·d) ]by gastrogavage.Rabbits in the DLP group were additionally administered with DLP [0.5 g/(kg·d) ]by gastrogavage.Equal volume of normal saline was administered to rabbits of the blank control group.The administration lasted for 4 successive weeks.Rabbitswere examined by abdominal aorta(optical coherence mography,OCT) 4 weeks later.All stent-implanted arteries in these animals were evaluated by histology.Blood lipids and inflammatory factors were detected as well.HE staining was performed after sampling.p-AKT protein expression was detected by Western blot.Results At post-PCI 4 weeks,TG,TC,LDL-C,Hs-CRP,M and TNF-α all significantly decreased in the conventional treatment group and the DLP group,when compared with pre-PCI in the same group as well as the blank control group at the same time point(P<0.01).Moreover,TC levels were lower in the DLP group than in the conventional treatment group(P<0.05).OCT and HE staining analyses showed as compared with the blank control group,the hyperplasia of neointima was symmetric,the degrees of neointima hyperplasia and luminal stenosis were attenuated(all P<0.01).The effects of DLP was superior to those of the conventional treatment group,but with no statistical difference between the two groups(P>0.05).Western blot showed that p-Akt expression significantly decreased in the conventional treatment group and the DLP group,as compared with the blank control group(all P<0.01),but with no statistical difference between the former two groups(P>0.05).Conclusion DLP could prevent ISR after implanting bare metal stents possibly by lowering inflammatory reactions and inhibiting AKT signal pathways.
Objective To observe roles and posible mechanism of Danlou Pill(DLP) for preventing bare metal stent(BMS) in-stent restenosis(ISR) of atherosclerosis rabbits,and to study potential mechanisms.Methods Abdominal aorta atherosclerosis model was established in 30 Japanese big ear rabbits by balloon injury and high-fat diet feeding after they took aspirin(25 mg/d) for 3 days.Four weeks later arteriography showed abdominal aorta atherosclerosis>30% occurred in 24 rabbits.After implanting bare metal stents,the rabbits were randomly divided into 3 groups,the blank control group,the conventional treatment group,and the DLP group,8 in each group.Rabbits in the conventional treatment group were administered with aspirin [50 mg/(kg·d),clopidogrel [25 mg/(kg·d) ],and rosuvastain [1 mg/(kg·d) ]by gastrogavage.Rabbits in the DLP group were additionally administered with DLP [0.5 g/(kg·d) ]by gastrogavage.Equal volume of normal saline was administered to rabbits of the blank control group.The administration lasted for 4 successive weeks.Rabbitswere examined by abdominal aorta(optical coherence mography,OCT) 4 weeks later.All stent-implanted arteries in these animals were evaluated by histology.Blood lipids and inflammatory factors were detected as well.HE staining was performed after sampling.p-AKT protein expression was detected by Western blot.Results At post-PCI 4 weeks,TG,TC,LDL-C,Hs-CRP,M and TNF-α all significantly decreased in the conventional treatment group and the DLP group,when compared with pre-PCI in the same group as well as the blank control group at the same time point(P<0.01).Moreover,TC levels were lower in the DLP group than in the conventional treatment group(P<0.05).OCT and HE staining analyses showed as compared with the blank control group,the hyperplasia of neointima was symmetric,the degrees of neointima hyperplasia and luminal stenosis were attenuated(all P<0.01).The effects of DLP was superior to those of the conventional treatment group,but with no statistical difference between the two groups(P>0.05).Western blot showed that p-Akt expression significantly decreased in the conventional treatment group and the DLP group,as compared with the blank control group(all P<0.01),but with no statistical difference between the former two groups(P>0.05).Conclusion DLP could prevent ISR after implanting bare metal stents possibly by lowering inflammatory reactions and inhibiting AKT signal pathways.
引文
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[10]杨振,洪铁,刘玉梅,等.丹蒌片对高脂血症及血管内皮损伤大鼠的保护作用[J].世界中西医结合杂志,2010,5(6):491-494.
[11]王富江,张鹏,于春泉,等.丹蒌片对心血管疾病的作用及相关成分的生物网络关系的探讨[J].中草药,2015,46(5):774-777.
[12]Morello F,Perino A,Hirsch E,et al.Phosphoinositide 3-kinase signaling in the vascular system[J].Cardiovasc Res,2009,82(2):261-271.
[2]Bosiers M,Deloose K,Keirs K,et al.Prevention and treatment of in-stent restenosis[J].J Cardiovasc Surgery,2010,51(4):591-598.
[3]Curcio A,Torella D,Indolfi C,et al.Mechanisms of smooth muscle cell proliferation and endothelial regeneration after vascular injury and stenting:Approach to therapy[J].Circulation,2011,75(6):1287-1296.
[4]Alfonso F,Byrne RA,Rivero F,et al.Current treatment of in-stent restenosis[J].J Am Coll Cardiol,2014,63(24):2659-2673.
[5]曾垂义,朱明军,王振涛.动脉粥样硬化病因病机浅议[J].辽宁中医药大学学报,2006,8(5):24-25.
[6]陈浩,苏伟,龚少愚,等.动脉粥样硬化中医“瘀毒”病因病机的研究进展[J].中西医结合心脑血管病杂志,2011,9(9):1104-1106.
[7]Nakazawa G,Nakano M,Otsuka F,et al.Evaluation of polymer-based comparator drug-eluting stents using a rabbit model of iliac artery atherosclerosis[J].Circ Cardiovasc Interv,2011,4(1):38-46.
[8]Kim MS,Dean LS.In-stent restenosis[J].Cardiovasc Therapeutics,2011,29(3):190-198.
[9]Amatruda CM,Bona Casas C,Keller BK,et al.From histology and imaging data to models for in-stent restenosis[J].Int J Artific Organs,2014,37(10):786-800.
[10]杨振,洪铁,刘玉梅,等.丹蒌片对高脂血症及血管内皮损伤大鼠的保护作用[J].世界中西医结合杂志,2010,5(6):491-494.
[11]王富江,张鹏,于春泉,等.丹蒌片对心血管疾病的作用及相关成分的生物网络关系的探讨[J].中草药,2015,46(5):774-777.
[12]Morello F,Perino A,Hirsch E,et al.Phosphoinositide 3-kinase signaling in the vascular system[J].Cardiovasc Res,2009,82(2):261-271.