转导C型钠尿肽基因对血管成形术后新生内膜增生及内皮功能的影响

目的 观察局部转导C型钠尿肽(CNP)基因对血管损伤后内膜增生及内皮功能的影响。方法 将84只雄性新西兰大白兔随机均分为正常、对照和实验3组。3组高脂饮食喂养,对照组和实验组以球囊损伤兔髂动脉建立动脉粥样硬化兔再狭窄模型。对照组建模后局部转导逆转录病毒载体携带的碱性磷酸酶基因,实验组建模后后局部转导逆转录病毒载体携带的CNP基因(PLXSN-CNP)。于高脂饮食喂养前及处死前检测各组血脂和血CNP水平,对损伤的髂动脉进行离体血管环张力实验, 进行病理和CNP免疫组化学检测,采用计算机图像分析仪测量动物血管管腔面积、内膜厚度、内膜面积、内膜面积/中膜面积。结果 对照组和实验组血CNP水平和血脂水平在术前和术后同一时间点比较无显著差异。实验组血管经Ach和L-Arg 预处理+Ach处理后,内皮依赖性舒张功能显著强于正常组和对照组(P<0.01) 而非内皮依赖性舒张功能各组间无显著差异(P>0.05),而经LMMA预处理+ Ach 处理后血管环舒张功能明显变差;实验组在转染局部表达CNP基因;球囊损伤后2周,实验组和对照组血管内膜面积、内膜厚度、内膜/中膜比值显著增加,但实验组显著低于对照组(P<0.01)。结论 CNP基因可成功转导损伤血管,并有效地在局限表达;局部转导CNP基因可有效抑制血管成形术后内膜增生,增进内皮功能。     

复方丹参滴丸、普罗布考对动脉损伤后内膜增殖与血管重塑的影响

目的：探讨复方丹参滴丸、普罗布考对兔髂动脉损伤后内膜增殖、血管重塑及血管内皮生长因子表达的影响。方法：雄性日本大耳白兔40只,随机平均分为对照组、普罗布考组、复方丹参滴丸组和联合组,高脂喂养两周后行髂动脉球囊内皮拉伤术,从术前3d开始对照组予单纯高脂喂养,治疗组分别以普罗布考（1．0g／只·d^-1）、复方丹参滴丸（300mg／只·d^-1）及两药联合灌喂至术后4周,取病变血管行病理形态学观察,免疫组化检测血管内皮生长因子（VEGF）和增殖细胞核抗原（PCNA）表达水平。结果：与对照组比较,普罗布考组、复方丹参滴丸组增殖内膜面积明显减小（P〈0．05）,普罗布考组内弹力膜包绕面积增大（P〈0．05）;与单独用药组比较,联合组内弹力膜包绕面积明显增大（P〈0．05）,但增殖内膜面积无改变（P〉0．05）;各治疗组VEGF、PCNA表达均较对照组明显减少（P〈0．05）。结论：复方丹参滴丸、普罗布考均可抑制动脉损伤后平滑肌细胞增殖,减轻内膜增生;普罗布考兼有改善血管重塑的作用,两药联合使用可取得改善血管重塑的协同效应,其机制可能与减少VEGF在血管内、中膜的表达水平有关。     

普罗布考和科素亚对血管成形术后生长因子表达的影响

目的 :研究普罗布考和科素亚对血管成形术后再狭窄的预防作用和对生长因子表达的影响。方法 :新西兰白兔30只均予高脂饮食 ,1周后进行髂动脉球囊拉伤术 ,随机分为对照组 (C组 )、普罗布考组 (P组 )、科素亚组 (L组 )。术后第 4周进行血管形态学检查 ,用免疫组化方法检测胰岛素样生长因子 - 1受体 (IGF- 1 R)、血管内皮生长因子(VEGF)、增殖细胞核抗原 (PCNA)表达。结果 :与 C组相比 ,P组和 L 组血管腔面积明显扩大 (P<0 .0 1 ) ,IGF- 1 R、VEGF和 PCNA表达明显减少 (P<0 .0 1 ) ,P组和 L组相比无显著性差异 (P>0 .0 5 )。结论 :普罗布考和科素亚可以显著减轻兔髂动脉血管成形术后再狭窄的形成 ,抑制 IGF- 1、VEGF和 PCNA的表达 ,而两药之间则无显著性差异     

Effects of tetrandrine on phenotypic modulation of vascular smooth muscle cells and expression of p38 MAPK as well as MKP-1 after intimal injury of rabbit carotid arteries

Objective： To study the effects of tetrandrine （Tet） on phenotypic modulation of vascular smooth muscle cells （VSMCs） and expression of p38 mitogen-activated protein kinase （p38MAPK） as well as mitogen-activated protein kinase phosphatase-1 （MKP-1） after vascular intimal injury. Methods： HE staining was used to analyze vascular morphology of sham-injured group, injured group and Tet-treated group at day 28. lmmunohistochemistry, Western blot and RT-PCR were respectively used to detect the expression change of smooth muscle a-actin （SMa-actin）, proliferation cell nuclear antigen （PCNA）, p38MAPK and MKP-1 of injured group and Tet group at days 7, 14 and 28 after balloon injury. Results： ① All layers of vascular wall in sham-injured group were intact at day 28. The neointimal area was significantly increased and the lumen area notably decreased in injured group at day 28. The neointimal proliferation in Tet treated group was less than that in injured group, and the lumen area of Tet group was significantly increased than that of injured group at day 28. ②Compared with the injured group, the expression of SMa-actin, PCNA, p38MAPK and MKP-1 of vascular wall in Tet group was no difference, and the neointimal proliferation condition was also basically as same as injured group at day 7 after injury. The expression of PCNA and p38MAKP in Tet group was obviously lower than that in injured group, and the expression of MKP-1 in Tet group was obviously higher than that in injured group at days 14 and 28 after injury. The expression of SMa-actin in Tet group was slightly higher than that in injured group at days 14 and 28 after injury. Conclusions： Tet could reduce neointimal proliferation by inhibiting VSMCs phenotypic modulation and p38MAPK signaling transduction pathway as well as its down regulation.     

粒细胞集落刺激因子对兔髂动脉球囊损伤后内膜修复和增生的影响

目的探讨重组人粒细胞集落刺激因子（rhG-CSF）对兔髂动脉球囊损伤后再内皮化和内膜增生的影响。方法将制模成功的56只新西兰大白兔随机分为2组,观察组皮下注射rhG-CSF 30μg/（kg.d）,7 d后经颈动脉行左髂总动脉球囊导管拉伤,术后14 d用伊文氏蓝染色、HE染色、免疫组织化学方法,观察血管再内皮化、新生内膜增厚及细胞增殖情况;对照组用生理盐水代替rhG-CS,其余同观察组。结果造模14 d后,观察组的内膜再生面积（An）和内膜损伤总面积（At）比值明显高于对照组[（68.60±6.25）%vs（46.60±3.36）%,P〈0.01];内膜厚度（Ti）/中膜厚度（Tm）比值明显低于对照组（1.53±0.14 vs 2.43±0.15,P〈0.01）。结论内皮前体细胞动员剂rhG-CSF能显著促进血管损伤后内皮化,有效抑制了支架内再狭窄的发生。     

重组生长激素对兔血管内皮功能的保护作用

目的研究重组生长激素(recombinant growth hormone,rGH)对高胆固醇饮食的新西兰兔动脉粥样硬化的作用及rGH对血管内皮功能的影响。方法健康新西兰白兔,均为雄性,兔龄4个月,体重(2.2±0.3)kg,随机分为rGH组、对照组(NC)、高胆固醇组(HC)观察高胆固醇饮食的条件下,rGH对血脂、一氧化氮(nitric oxide,NO)、内皮素(endothelin,ET)和动脉粥样硬化的效应。测定血管环对乙酰胆碱(acetylcholine,Ach)、硝酸甘油(nitrogenglycerine,NG)的舒张反应。结果(1)rGH组动脉粥样硬化的面积和发生率均低于对照组。(2)rGH组对Ach的最大舒张反应明显高于HC组(P<0.01),但对NG的最大舒张反应rGH组与HC组无明显差异。结论rGH能够有效地抑制高胆固醇饮食条件下的动脉粥样硬化的损伤程度,并改善高胆固醇饮食条件下血管内皮细胞的乙酰胆碱依赖性舒张功能。     

192Ir 血管内照射防止兔球囊血管成形术后再狭窄

目的　本研究旨在检验192 Ir血管内照射对兔球囊血管成形术后再狭窄的作用。方法　建立兔髂动脉粥样硬化模型 ,对病变血管行球囊成形术 ,同时随机分为对照组 ,10Gy照射组和 18Gy照射组。以导管导入192 Ir放射性导丝对照射组动物的扩张处进行血管内照射。 4周后处死动物 ,取出血管标本 ,进行病理组织学分析。结果　 18Gy照射组最终管腔面积较对照组及 10Gy照射组大 (P <0 0 5) ,18Gy照射组内膜面积较小 (P <0 0 5)。结论　本动物实验提示192 Ir血管内照射可防止球囊血管成形术后再狭窄 ,其效果与照射剂量相关 ,其机制涉及抑制新生内膜增殖。     

雷帕霉素洗脱支架抑制猪颈动脉成形术后近期再狭窄的实验研究

目的:研究自膨式雷帕霉素洗脱支架防治猪颈动脉血管成形术后近期再狭窄的有效性安全性,及其作用机制.方法:国产小型猪6只,分别行双侧颈总动脉球囊扩张损伤后,随机分为对照组(裸支架组)和实验组(雷帕霉素洗脱支架组),各置入6枚.术后4周重复动脉造影后处死动物.取出支架段血管,测算支架处血管管腔面积、新牛内膜厚度与面积及管腔狭窄百分比以评价内膜增生程度.应用TUNEL法检测新生内膜细胞凋亡指数(apoptotic index,AI),免疫组化检测血管平滑肌细胞中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、Bcl-2、Bax表达水平.结果:雷帕霉素洗脱支架组支架内管腔面积大于裸支架组(P<0.05);新生内膜面积小于裸支架组(P<0.05);新生内膜厚度小于裸支架组(P<0.05);细胞凋亡多于裸支架组(P<0.05):PCNA阳性细胞及Bcl-2表达低于裸支架组(P<0.05);Bax表达高于裸支架组(P<0.05).结论:雷帕霉素洗脱支架能抑制新生内膜形成.在支架植入后4周能预防猪颈动脉血管成形术后近期再狭窄的形成.可能通过上调Bax,下调Bcl-2的表达.从而抑制血管平滑肌细胞增殖发挥作用.     

192Ir endovascular irradiation prevents restenosis after balloon angioplasty in rabbit

Objective　To examine the effect of endovascular irradiation on restenosis after balloon angioplasty in rabbit. Methods　After the establishment of rabbit iliac atherosclerosis model, balloon angioplasty was performed at the lesion segment of the iliac artery. Rabbits were randomly divided into three groups: control group, 10 Gy irradiated group and 18 Gy irradiated group. Endovascular irradiation was performed for irradiated groups at the dilated sites by introducing the 192Ir radioactive guidewire through a catheter. After four weeks, the animals were killed and the target segments were cut down. Histopathologic and morphometric analyses were carried out. Results　The mean final lumen area in the 18 Gy group was larger than that in the control or 10 Gy group (P&lt;0.05). The intimal area in the 18 Gy group was smaller (P&lt;0.05). Conclusions　192Ir endovascular irradiation may prevent restenosis after balloon angioplasty. The effect is related to the delivered dose. The mechanism is involved in inhibition of neointimal proliferation.     

普罗布考和科素亚对兔血管成形术后生长因子的影响

目的：研究普罗布考和科素亚对兔血管成形术后再狭窄的预防作用及其对生长因子表达的影响。方法：雄性新西兰白兔40只,随机分为高胆固醇组、普罗布考组、科素亚组和联合用药组。1周后进行髂动脉球囊拉伤术,术后4周进行弹力纤维染色,用免疫组化检测血管胰岛素样生长因子-Ⅰ受体（insulin-like growth factor-Ⅰ receptor,IGF-IR）和内皮生长因子（vascular endothelial growth factor,VEGF）表达。结果：与高胆固醇组相比,普罗布考组、科素亚组和联合用药组管腔面积明显扩大（P〈0．01）,内膜面积明显减少（P〈0．05）,IGF-IR和VEGF表达明显减少（P〈0．01）,但3组间相比差异无统计学意义（P〉0．05）。结论：普罗布考和科素亚可以显著减轻兔髂动脉血管成形术后再狭窄的形成,抑制IGF—IR和VEGF的表达。联合用药与单独用药之间差异无统计学意义。