辛伐他汀对支架置入后兔腹主动脉内膜增生的影响

目的 观察辛伐他汀对兔腹主动脉支架置入后内膜增殖的影响.方法 30只新西兰大白兔随机分为对照组和辛伐他汀治疗组.采用含1.5%胆固醇的高脂饮食加腹主动脉内皮剥脱术制作兔腹主动脉粥样硬化模型.内皮剥脱术后第12周实验组和对照组服用阿司匹林25 mg/d,氯吡格雷12.5 mg/d, 3 d后,分别行支架置入术.术后实验组继续服用辛伐他汀5 mg/d,服药至第30天处死动物,取腹主动脉含支架段血管,进行血管壁组织形态学变化观察和检测细胞周期抑制蛋白P27kip1、增殖细胞核抗原(PCNA)在各组的表达量的变化.结果 血管超声发现内皮剥脱术后第10周实验组和对照组腹主动脉均可见有不同程度的粥样硬化斑块和血管内狭窄.组织形态学观察发现服用辛伐他汀的实验组兔腹主动脉支架段内的血管内膜厚度(0.107±0.072 mm,与对照组0.133±0.047 mm比,P=0.006)、新生内膜面积(0.975±0.084 mm2,与对照组1.350±0.043 mm2比,P=0.001)均明显降低,且血管的狭窄程度较轻(20.460%±2.325%,与对照组31.020%±1.904%比,P=0.002).实验组兔腹主动脉支架段内的血管新生内膜中的血管平滑肌细胞(VSMC)的胞核P27kipl蛋白表达量明显升高(7.149±0.305,与对照组2.997±0.310比,t=9.551,P＜0.05),而血管新生内膜中VSMC的胞核PCNA表达量明显降低(着色强度IS为3.003±0.192, 与对照组着色强度IS 5.268±0.475比,t=4.423,P＜0.05).结论 辛伐他汀能明显抑制支架置入术后血管内膜增生.其机制可能为通过上调P27kip1蛋白表达量,使增殖标志物PCNA表达量降低,而对VSMC增殖周期起负调控作用,达到抑制VSMC增殖和新生内膜的增生.     

雌激素洗脱支架植入兔腹主动脉对内膜增生及内皮化的影响

目的评价雌激素洗脱支架对在体兔腹主动脉内膜增生及内皮化的影响。方法雄兔高脂喂养制成高脂血症模型后分三组,分别于腹主动脉植入裸金属支架、磷酸胆碱涂层支架和17β雌二醇洗脱支架,前两种支架作为对照。每组18只,各组于术后2、4及12周取出6只兔的支架段腹主动脉,测算支架处血管腔面积、新生内膜厚度和面积及管腔狭窄百分比以评价内膜增生程度。应用免疫组织化学染色法分析各时相支架段血管内膜Ⅷ因子阳性率以评估其再内皮化程度。结果3组不同支架植入后导致的血管损伤积分在各时相基本相同(2.17±0.22、2.18±0.21和2.17±0.19,P>0.05);各组支架植入2周时血管内膜已经增厚,在12周时管腔狭窄均<50%,但12周时雌二醇洗脱支架组新生内膜面积较裸金属支架组减少36%(P<0.01),磷酸胆碱涂层支架组与裸金属支架组相比无明显差别;2周与12周时新生内膜面积比在雌二醇洗脱支架组、磷酸胆碱涂层支架组、裸金属支架组分别为0.77、0.61和0.61(P<0.01)。2周时雌二醇洗脱支架组内皮化率明显高于裸金属支架组及磷酸胆碱涂层支架组(78.4%±2.3%比61.4%±3.4%及62.8%±2.9%,P<0.01),4周时各组血管内膜均接近完全内皮化。结论雌二醇洗脱支架可明显减少血管内支架植入后的内膜增生,加速支架段血管的再内皮化,具有良好的对抗再狭窄的应用前景。     

雌二醇洗脱支架抑制血管内膜增生的实验研究

目的观察雌二醇(E2)洗脱支架植入对高脂喂饲兔腹主动脉内膜增生的影响,并探讨其可能的机制。方法雄兔高脂喂饲后分别于腹主动脉植入裸金属支架、磷酸胆碱(PC)涂层支架和17β-E2洗脱支架,应用HE染色、免疫组化染色及蛋白印迹方法观察17β-E2洗脱支架抑制内膜增生的作用及机制。结果支架植入术后血管壁ERK迅速活化,磷酸化ERK(p-ERK)在术后0.5 h时达峰值。各组支架植入12周时血管内膜均明显增厚。E2洗脱支架组新生内膜面积较裸金属支架组减少36%。支架植入后0.5 h时E2洗脱支架组p-ERK表达明显低于裸金属支架组。2周时E2洗脱支架组内皮化率明显高于裸金属支架组及PC涂层支架组。结论 E2洗脱支架安全、有效,可明显减少实验兔支架植入后的血管内膜增生;与普通裸金属支架对比,E2洗脱支架能够加速支架段血管的再内皮化;丝裂原激活蛋白激酶ERK1/2可能介导了支架植入后血管平滑肌细胞的增殖和内膜增生。     

消瘀片消退兔腹主动脉粥样斑块作用的研究

目的 观察消瘀片对兔腹主动脉粥样斑块的消退作用。方法 采用高脂饮食８ｗ加主动脉内膜剥脱术帛成兔腹主动脉粥样硬化模型,通过血管腔内超声技术、光镜和电镜,检查口服消瘀片１６ｗ后兔腹主动脉粥样斑块的消长变化。结果 血管腔内超声检查显示,粥样硬化组管壁呈弥漫性增厚,腔内有环形或半月状粥样斑块低回声区,用消瘀片治疗后,管壁增厚不明显,仅可见散在或短弧形粥样斑块回声区,粥样斑块厚度和斑块面积与粥样硬化组相比明     

高脂血症对内皮剥脱术后血管炎症反应的影响

目的探讨高脂血症对内皮剥脱术后血管炎症反应的影响。方法建立大鼠主动脉内皮剥脱后内膜增生模型,利用免疫组化及Western blot方法检测血管壁NF-κB和iNOS的表达变化,并结合形态学分析研究高脂血症大鼠内皮剥脱后血管炎症反应及新生内膜增生情况。结果主动脉内皮剥脱后内膜呈弥漫性增厚,管腔变小,增厚的内膜以VSMC为主,中膜VSMC排列紊乱。高脂血症明显促进了增生的内膜中NF-κB和iNOS的表达。结论高脂血症通过促进NF-κB表达进而诱导iNOS的表达,加剧了内皮剥脱后的血管炎症反应。     

以球囊携带液体188铼兔颈动脉腔内照射预防再狭窄的实验研究

目的　评价以球囊携带液体1 88铼 (1 88Re)兔颈动脉腔内照射预防再狭窄的可行性及作用。方法　 12只兔颈动脉过大球囊损伤内膜后行1 88Re放射治疗 ,随机分为对照组 (n =6 )和照射组(n =6 ) ,管腔下 0 0 5mm处的吸收剂量为 15Gy。全部兔饲养 1周后活杀 ,取病理组织学标本进行分析。结果　照射组内膜面积明显小于对照组 [(0 0 4± 0 0 6 )mm2 vs (0 16± 0 0 4)mm2 ,P <0 0 5 ],管腔面积明显大于对照组 [(0 6 5± 0 0 5 )mm2 vs (0 35± 0 0 3)mm2 ,P <0 0 5 ],血管面积大于对照组[(1 0 4± 0 2 3)mm2 vs (0 81± 0 0 5 )mm2 ,P =0 0 4]。照射中央区管腔面积大于边缘区 [(0 6 5± 0 0 5 )mm2 vs(0 2 5± 0 0 6 )mm2 ,P <0 0 5 ],内膜面积小于边缘区 [(0 0 4± 0 0 6 )mm2 vs(0 12± 0 10 )mm2 ,P<0 0 5 ],内弹力板面积大于边缘区 [(0 70± 0 0 4)mm2 vs(0 37± 0 14)mm2 ,P =0 0 6 ],血管面积大于边缘区 [(1 0 4± 0 2 4)mm2 vs (0 6 3± 0 17)mm2 ,P <0 0 5 ]。结论　以球囊携带液体1 88Re血管腔内照射通过抑制内膜增生及血管重塑来减少再狭窄 ;边缘效应主要是由于血管的收缩性重塑引起的。     

血管紧张素转化酶抑制剂对兔腹主动脉球囊损伤后的影响

目的:研究血管紧张素转化酶抑制剂(ACEI)对兔腹主动脉球囊损伤后的影响及作用机制。方法:雄性新西兰大白兔随机分为ACEI组和对照组,每组10只。球囊损伤腹主动脉后,ACEI组给予福辛普利5mg.kg-1.d-1,对照组不给予药物处理。实验4周后,取腹主动脉标本,使用计算机辅助形态分析系统比较2组新生内膜、中膜及管腔面积,测定血清、组织肝细胞生长因子(HGF)浓度以及与新生内膜面积的相关关系。结果:ACEI组新生内膜面积显著低于对照组[(0.048±0.011)mm2∶(0.124±0.021)mm2,P<0.001];管腔面积对照组显著低于ACEI组[(1.920±0.140)mm2∶(2.290±0.260)mm2,P=0.001];血管中膜面积2组差异无统计学意义[(0.890±0.130)mm2∶(0.990±0.120)mm2,P>0.05]。2组血浆HGF浓度差异无统计学意义[(485±84)ng/L∶(507±106)ng/L,P>0.05],组织HGF浓度ACEI组显著高于对照组[(49.9±5.5)ng/g∶(32.7±4.5)ng/g,P<0.001];单因素相关分析发现新生内膜面积与组织HGF浓度呈负相关(r=-0.943,P<0.001)。结论:ACEI可以减轻兔腹主动脉球囊损伤后新生内膜的形成,增加管腔面积,升高组织HGF浓度而对血浆HGF浓度无影响。ACEI减轻血管球囊损伤后的新生内膜形成部分通过升高组织HGF发挥作用。     

缬沙坦涂层支架对支架术后再狭窄中胶原沉积的影响

目的评价缬沙坦涂层支架对支架置入后新生内膜中胶原沉积的影响及其预防支架内再狭窄的可行性。方法18只新西兰大白兔分为裸支架组,载体涂层支架组,缬沙坦涂层支架组3组。采用多层涂布技术制备缬沙坦涂层支架和载体涂层支架。分别将裸支架、载体涂层支架及缬沙坦涂层支架置入兔腹主动脉。术前、术后及支架置入3个月后分别行定量腹主动脉造影(QCA)测量血管直径。3个月后处死实验兔,分别测定3组支架血管段的管腔面积,内外弹力膜围绕面积,新生内膜面积及最大内膜厚度并做比较。将支架血管段进行MASSON染色,观察胶原沉积情况,天狼星红-苦味酸染色进一步观察胶原的类型。结果裸支架组(n=8),载体涂层支架组(n=8),缬沙坦涂层支架组(n=10),QCA测量的术前、术后及3个月后腹主动脉直径相似。缬沙坦组管腔面积最大,新生内膜面积最小,裸支架组、载体涂层支架组、缬沙坦涂层支架组平均管腔面积分别为(4345548±125822)μm2,(4302061±167952)μm2,(5016269±207934)μm2,平均新生内膜面积分别为(1119635±163503)μm2,(1135636±136555)μm2,(441577±74099)μm2,平均最大内膜厚度分别为(240±30)μm,(192±21)μm,(116±12)μm。MASSON染色可见新生内膜中主要是胶原沉积,天狼星红-苦味酸染色发现胶原沉积主要为Ⅲ型胶原,间或有Ⅰ型胶原。结论缬沙坦涂层支架主要是通过抑制胶原沉积抑制支架置入后血管内膜增生发挥其防治支架内再狭窄作用的。     

放射性镍钛合金血管内支架的实验研究

目的　观察 85 .1kBq(2 .3μCi)放射性NiTi合金支架对兔腹主动脉新生内膜的影响及其生物相容性。方法　 1999～ 2 0 0 1年哈尔滨医科大学第一临床医学院心内科将放射性NiTi合金支架 (n =8)和非放射性NiTi合金支架 (n =8)分别植入兔腹主动脉内 ,3个月后行血管造影、光镜及透射电镜、肝功能、肾功能、骨穿涂片检查。结果　血管造影显示两组管腔均通畅 ,未见管腔狭窄及支架边缘狭窄 ;放射性支架组新生内膜厚度明显低于对照组 ,新生内膜平滑肌细胞 (SMCs)明显减少 ,中膜的厚度和SMCs两组无显著性差异 ,两组新生血管内膜均完全内皮化 ;两组肝功能、肾功能无显著性差异 ;骨髓增生均正常。结论　 85 .1kBq(2 .3μCi)的放射性NiTi合金血管内支架可抑制血管新生内膜增生 ,具有良好的生物相容性。     

以球囊携带液体188Re兔颈动脉腔内照射对再狭窄的预防

目的评价以球囊携带液体188Re兔颈动脉腔内照射预防再狭窄的可行性及作用.方法12只兔颈动脉用过大球囊损伤内膜后行188铼(188Re)放射治疗,随机分为对照组(n=6)和照射组(n=6),管腔下0.05 mm处的吸收剂量为15 Gy.全部兔饲养3周后活杀,取病理组织学标本进行分析.结果照射组内膜面积明显小于对照组[(0.17±0.12) mm2∶(0.41±0.05) mm2,P<0.05],管腔面积明显大于对照组[(0.61±0.15) mm2∶(0.36±0.05) mm2,P<0.05],血管面积无明显的变化[(1.22±0.11) mm2∶(1.15±0.08) mm2,P>0.05].结论以球囊携带液体188Re血管腔内照射操作简单易行;可通过抑制内膜增生减少再狭窄.     

阿托伐他汀对THP1巨噬细胞脂质蓄积及CD36表达的影响

目的观察阿托伐他汀对氧化型低密度脂蛋白诱导的THP1巨噬细胞脂质蓄积及CD36表达的影响。方法用50mg/L氧化型低密度脂蛋白与不同浓度(0μmol/L、0.312μmol/L、1.25μmol/L和5μmol/L)的阿托伐他汀共同孵育24h,空白组作为对照,用液体闪烁计数法检测细胞[3H]胆固醇流入情况,油红     

Endovascular abdominal aortic stenosis treatment with the optimed self‐expandable nitinol stent

Purpose: To evaluate the safety and feasibility of self‐expandable stents (OptiMed) for treatment of abdominal aortic stenosis in the situations in which the aortic stenosis locates near the origin of celiac, superior mesenteric, renal and inferior mesenteric arteries. Methods: Five consecutive patients scheduled for endovascular treatment of abdominal aortic stenosis by self‐expandable nitinol stent (Sinus‐Aorta/OptiMed) implantation. The diameter of the stent was chosen as 10–30% more than that of the normal portion of the aorta above the stenosis. Long stents of 60 mm or longer were chosen. After stent deployment, balloon postdilation was performed with a balloon in patients with residual gradient > 5 mm Hg. Results: All patients were successfully treated with the OptiMed stents. The balloon predilation was performed in one patient due to severe stenosis. The mean diameter and length of the stents deployed were 20.4 ± 2.9 (range, 16–24 mm) and 64 ± 8.9 (range, 60–80 mm), respectively. The balloon postdilation was performed in all cases. The mean diameter of the balloons was 13.6 ± 1.5 (range, 12–15 mm). The mean diameter of stenosis increased from 4.8 ± 1.9 to 14.4 ± 1.8 mm after stent placement. The mean peak systolic gradient decreased from 46.8 ± 31.5 mm Hg to 0.8 ± 1.8 mm Hg. During follow‐up (22.8 ± 14.3 months), none of the patients had restenosis within the stent, occlusion of any branches of the aorta, or other related complications. Conclusions: In our small series, we observed that abdominal aortic stenosis can be successfully and effectively treated with OptiMed stents in the situations in which the stenotic segment is located next to the origins of the main visceral branches of abdominal aorta. © 2009 Wiley‐Liss, Inc.     

Vascular stenting in normal and atherosclerotic rabbits. Studies of the intravascular endoprosthesis of titanium-nickel-alloy

Percutaneous transluminal balloon angioplasty would be more effective if the rate of recurrent stenosis were reduced. To evaluate the prevention of restenosis after percutaneous transluminal angioplasty, intravascular endoprosthetic stents of titanium-nickel-alloy were implanted transluminally in seven normal and 21 atherosclerotic rabbits. In normal rabbits, a 3.5-mm diameter stent was implanted in the aorta and a 2.5-mm diameter stent in the right iliac artery, which were followed with serial angiograms from 6 weeks (n = 7) to 8 months (n = 4). There was a mean stenosis of 13.1% in the 2.5-mm and 13.6% in the 3.5-mm stent. There was no significant narrowing compared with the adjacent control segments of artery; histopathology showed a thin, fibrous neointima with smooth muscle cells. Each atherosclerotic rabbit was balloon dilated at two separate stenotic sites; each site was 2.0 cm in length. The aortic site (with 28.8 +/- 13.8% mean stenosis [+/- SD]) was dilated with a 3.5-mm balloon, and the iliac site (with 36.5 +/- 14.2% stenosis) was dilated with a 2.5-mm balloon. In each site, an intravascular stent of corresponding diameter and 7-mm length was implanted in one half of the dilated segment, assigned randomly, and the other half served as the angioplasty control. Angiographically observed restenosis rates and the corresponding histopathology were similar in the atherosclerotic segments that had angioplasty alone versus the atherosclerotic segments that had angioplasty plus stenting. The mean neointimal thickness in the aortas and iliac arteries, respectively, measured 247 +/- 181 microns (+/- SD) and 218 +/- 77 microns after 6 weeks (n = 8) versus 321 +/- 168 and 308 +/- 189 microns after 20 weeks (n = 5, p = NS). At 20 weeks follow-up, there was 29.1 +/- 29.8% (median, 16.4%) stenosis in the aortic stent versus 38.9 +/- 24.1% (median, 34.0%) stenosis in the percutaneous transluminal angioplasty control segment of aorta (n = 5, p = NS) and 81.4 +/- 25.5% stenosis in the iliac artery stent versus 89.3 +/- 15.3% stenosis in the PTA control segment of the right iliac artery (n = 5, p = NS). Comparing stenotic arterial segments treated with angioplasty alone with angioplasty plus intravascular stenting in the atherosclerotic rabbits showed that there was no significant difference in either the histopathologic changes or the restenosis rates.     

骨髓间充质干细胞移植加重大鼠主动脉血管成形术后再狭窄程度

目的探讨骨髓间充质干细胞（MSCs）移植对大鼠血管成形术后再狭窄的影响。方法随机将大鼠分为正常对照、损伤和损伤加MSCs移植组,用经皮冠状动脉腔内成形术（PTCA）导管扩张大鼠胸腹主动脉创建动脉损伤模型。贴壁法培养大鼠MSCs,经4,6-联脒-2-苯基吲哚（DAPI）荧光标记后,以2×10^6数量经导管注入移植组大鼠主动脉内。术后第1、2、6周取材寻找DAPI标记的MSCs,行组织形态学及血小板衍生的生长因子受体（PDGFR）家族干细胞因子的受体（c—kit）,增殖细胞核抗原（PCNA）,平滑肌肌动蛋白（αSMA）免疫组化分析。结果移植术后1～2周,可见DAPI标记MSCs归巢到损伤内膜表面或中膜近内膜处,并表达d—SMA。移植组和损伤组新生内膜表面均表达少量c-kit,两组之间无明显差别。正常对照组血管中膜α-SMA均匀强表达,PCNA表达微弱,无新生内膜。移植组新生内膜中PCNA和α—SMA表达均强于损伤组。术后6周,移植组新生内膜／中膜面积百分比和管腔面积狭窄率均较损伤组明显增加,差异具有统计学意义。结论经主动脉移植的骨髓MSCs可归巢到严重受损的主动脉内膜上,并分化为平滑肌样细胞,参与新生内膜的形成,加重大鼠血管成形术后再狭窄程度。     

普罗布考抑制兔颈动脉内膜切除术后再狭窄的实验研究

目的观察抗氧化剂普罗布考对颈动脉内膜切除术(CEA)后早期再狭窄形成过程的影响。方法采用血管内膜气体损伤结合高脂饲料喂养的方法建立新西兰兔颈动脉粥样硬化动物模型,随机分为实验组(30只)和对照组(30只),在此动物模型基础上行CEA,实验组在术前14天开始用普罗布考(0.6 g.kg-1.d-1)胃管灌入,连续用药,运用超声、病理等方法从影像学和组织学的角度,观察其在CEA后对新内膜的作用。结果实验组术后新内膜的厚度和面积较对照组明显减小,内膜与中膜的比例显著降低,血管残腔面积增加,狭窄率明显低于对照组,双功超声及术后病理测量均证实上述结果。结论抗氧化剂普罗布考可能通过其复杂的结构和多方面的作用机制,起到抗再狭窄的作用。     

Stent redilation in canine models of congenital heart disease: Pulmonary artery stenosis and coarctation of the aorta

In a canine puppy model, pulmonary artery stenosis was created by banding the left pulmonary artery to 30–40% of its original diameter. Animals underwent right heart catheterization and angiography 1–2 mo later, and Palmaz P308 stents were implanted. Stent redilation was performed 3–5 mo later. One mo postredilation, the animals were restudied and sacrificed. Coarctations of the aorta were created by transverse aortic incision and longitudinal repair. P308 stent implantation was performed 2–3 mo later. Stent redilation was performed after 6–10 mo, and the animals were restudied and sacrificed 1–2 mo later. Stent implantation was performed in 6 puppies with pulmonary artery stenosis, as 2 animals developed postoperative pulmonary arterial hypoplasia, precluding stenting. The stenosis diameter increased from 4.8 ± 0.5 mm to 7.4 ± 0.6 mm (mean ± SE) following stenting (P = 0.005), and increased further to 9.2 ± 0.7 mm following redilation (P < 0.001). There were no significant vessel tears or ruptures. Coarctation stenting was performed in 8 animals. The coarctation was dilated from 5.8 ± 0.9 mm to 9.8 ± 0.6 mm (P < 0.001), and to 13.5 ± 0.5 mm at redilation (P = 0.002). Redilation could not be performed in 1 animal. Aortic rupture and death occurred in 2 of 7 animals at redilation. Stent implantation and redilation in experimental pulmonary artery stenosis appears safe and effective. Though stent implantation for coarctation of the aorta appears safe, there was a 28% aortic rupture rate at stent redilation in this model. © 1996 Wiley-Liss, Inc.     

镍钛自膨胀支架置入血管后细胞凋亡与增生的实验观察

目的　血管内支架置入后的再狭窄是尚未解决的主要课题 ,本研究对置入镍钛 (NITI)自膨胀支架的动物进行研究 ,观察支架置入后血管平滑肌细胞 (VSMC)的凋亡与增生的关系 ,为再狭窄的防治提供新的方法。方法　在兔的腹主动脉内置入 30个NITI合金自膨胀支架 ,按不同时间处死动物 ,采用电镜和 3′ 末端DNA原位标记法 (TUNEL)观察VSMC的凋亡。结果　从支架置入后的 2 4h到 8周 ,支架置入部位均可见到凋亡的VSMC ,3～ 6周时 ,凋亡达到高峰 ,8周以后凋亡细胞开始减少。凋亡的细胞主要分布于血管的新生内膜层 ,但中膜层也存在有少量的凋亡细胞。结论　NITI自膨胀支架置入后 ,不仅有SMC的增生 ,也有SMC的凋亡。     

多沙唑嗪对血管狭窄和血清一氧化氮的影响

目的探讨多沙唑嗪对兔腹主动脉球囊损伤后血管狭窄的影响,及其与血清一氧化氮、血管内膜中膜平滑肌细胞增生的关系。方法23只新西兰兔随机分为正常对照组、球囊损伤组、多沙唑嗪组。正常对照组不予任何方式处理。另两组行腹主动脉球囊损伤术,同时多沙唑嗪组应用多沙唑嗪控释片4mg/d,观察各组血清一氧化氮以及血管损伤处血管狭窄、血管内膜中膜增殖细胞核抗原(PCNA)的变化。结果应用多沙唑嗪4周后多沙唑嗪组血清一氧化氮含量增高,血管损伤处血管内膜、外膜增生减轻,新生内膜面积减少,管腔面积增加,内弹力层和外弹力层包围面积增加,血管内膜中膜PCNA阳性平均灰度降低。结论多沙唑嗪可以抑制球囊损伤后兔腹主动脉血管的狭窄,抑制血管内膜中膜平滑肌细胞增殖,增加血清一氧化氮含量。     

胱抑素C在兔血管成形术后再狭窄中对血管外膜的影响

目的探讨兔腹主动脉血管成形术后胱抑素C水平变化对兔腹主动脉再狭窄血管外膜的影响及机制。方法选择新西兰大白兔48只,随机分为损伤组、治疗组(胱抑素C单克隆抗体治疗)、对照组,每组16只。分别于术前和术后8h、1d、1周、3周、6周取外周静脉血,检测血清中胱抑素C水平。术后6周取腹主动脉行HE染色、血管形态计量分析和血管外膜细胞计数;同时行平滑肌肌动蛋白、增殖细胞核抗原(PCNA)免疫组织化学染色,计算PCNA增殖指数。以血管重构指数、外弹力板围绕面积(EELA)、内弹力板围绕面积(IEIA)变化评价血管重构情况,以剩余狭窄率、血管腔面积变化衡量血管狭窄情况。结果与对照组比较,损伤组血管腔面积、EELA、IELA明显增大,血管重构指数为0.871,剩余狭窄率为33.1%。治疗组胱抑素C水平较损伤组明显下降,血管腔面积、EELA、IELA缩小程度较损伤组明显减轻,血管重构指数为0.748,剩余狭窄率为19.7%(P<0.05)。相关分析显示,胱抑素C水平与血管腔面积、新生内膜面积、IELA、EELA及PCNA阳性细胞数呈正相关(P<0.01)。结论兔腹主动脉球囊损伤后血管外膜细胞被激活,发生增殖、表型转化,参与了血管重构及血管再狭窄发生。胱抑素C水平高表达是发生腹主动脉狭窄的独立危险因素。     

复方丹参滴丸预防兔血管再狭窄的实验研究

目的探讨复方丹参滴丸预防再狭窄的可能机制。方法健康成年二级雄性日本大耳白兔30只,体重2.5~3.0公斤。随机分为三组:正常对照组10只,模型组10只(球囊内膜剥脱加高胆固醇饮食),治疗组10只(球囊内膜剥脱加高胆固醇饮食以及复方丹参滴丸150mg/d)。八周后处死各组动物,取兔的髂动脉标本行病理形态学观察以及采用免疫组化方法分析基质金属蛋白酶(MMPs)MMP2,MMP9的表达。结果(1)复方丹参滴丸组较模型组,血管腔直径狭窄减轻27.8%;内膜厚度减少41%,内膜面积减少52%,内膜厚度和中膜厚度比减少22%、面积比减少38%,各组之间有显著性差异(P<0.01)。(2)模型组和对照组比较其MMP2、MMP9明显增加,复方丹参滴丸组和模型组相比,复方丹参滴丸组MMP-2、MMP-9的表达低于模型组。(3)内膜的增生以及管腔的狭窄程度与MMP2、MMP9有很好的相关性(γ=0.896P<0.01)。结论MMP在再狭窄形成中起了重要的作用;复方丹参滴丸能够明显抑制血管损伤后的内膜增生。