Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet

Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate the role of endoplasmic reticulum stress(ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet(HFD)mice.Methods CCAAT-enhancer-binding protein-homologous protein(CHOP)knockout(KO)mice were created.Mice were fed with HFD to produce HFD model.AVGs model were applied in the groups of WT ND,WT HFD,and CHOP KO HFD.Human umbilical vein endothelial cells(HUVECs)were cultured with oxidized low density lipoprotein(ox-LDL)(40 mg/L)for the indicated time lengths(0,6,12,24 h).ERS inhibitor tauroursodeoxycholic acid(TUDCA)was used to block ERS.Immunohistochemical staining was used to observe the changes of ICAM1.Changes of ERS were detected by real-time RT-PCR.Protein expression levels and ERS activation were detected by Western blotting.Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay.Results HFD increased neointima formation in AVGs associated with endothelial dysfunction.At the same time,ERS was increased in endothelial cells(ECs)after AVGs in mice consuming the HFD.In vitro,ox-LDL was found to stimulate ERS,increase the permeability of the EC monolayer,and cause endothelial dysfunction.Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL.In vivo,knockout of CHOP(CHOP KO)protected the function of ECs and decreased neointima formation after AVGs in HFD mice.Conclusion Inhibiting ERS in ECs could improve the function of AVGs.

Enhanced caveolin-1 expression in smooth muscle cells: Possible prelude to neointima formation

AIM: To study the genesis of neointima formation in pulmonary hypertension(PH), we investigated the role of caveolin-1 and related proteins. METHODS: Male Sprague Dawley rats were given monocrotaline(M, 40 mg/kg) or subjected to hypobaric hypoxia(H) to induce PH. Another group was given M and subjected to H to accelerate the disease process(M + H). Right ventricular systolic pressure, right ventricular hypertrophy, lung histology for medial hypertrophy and the presence of neointimal lesions were examined at 2 and 4 wk. The expression of caveolin-1 and its regulatory protein peroxisome proliferator-activated receptor(PPAR) γ, caveolin-2, proliferative and antiapoptotic factors(PY-STAT3, p-Erk, Bcl-x L), endothelial nitric oxide synthase(e NOS) and heat shock protein(HSP) 90 in the lungs were analyzed, and the results from M + H group were compared with the controls, M and H groups. Double immunofluorescence technique was used to identify the localization of caveolin-1 in pulmonary arteries in rat lungs and in human PH lung tissue. RESULTS: In the M + H group, PH was more severe compared with M or H group. In the 4 wk M+H group, several arteries with reduced caveolin-1 expression in endothelial layer coupled with an increased expression in smooth muscle cells(SMC), exhibited neointimal lesions. Neointima was present only in the arteries exhibiting enhanced caveolin-1 expression in SMC. Lung tissue obtained from patients with PH also revealed neointimal lesions only in the arteries exhibiting endothelial caveolin-1 loss accompanied by an increased caveolin-1 expression in SMC. Reduction in e NOS and HSP90 expression was present in the M groups(2 and 4 wk), but not in the M + H groups. In both M groups and in the M + H group at 2 wk, endothelial caveolin-1 loss was accompanied by an increase in PPARγ expression. In the M + H group at 4 wk, increase in caveolin-1 expression was accompanied by a reduction in the PPARγ expression. In the H group, there was neither a loss of endothelial caveolin-1, eNOS or HSP 90, nor an increase in SMC caveolin-1 expression; or any alteration in PPARγ expression. Proliferative pathways were activated in all experimental groups. CONCLUSION: Enhanced caveolin-1 expression in SMC follows extensive endothelial caveolin-1 loss with subsequent neointima formation. Increased caveolin-1 expression in SMC, thus, may be a prelude to neointima formation.

Effect of adenoviral vector-mediated rat antisense AT1B gene transfer on neointima proliferation after rat carotid injury

Objective: Angiotensin Ⅱ is a growth-promoting factor for vascular smooth muscle cells in culture andin the intact animal. The biological effects of angiotensin Ⅱ are manifested only by binding to specific receptors oncell membranes. In the study, we observed that the effect of rat antisense AT1B gene transfer mediated by adenoviral vector-on neointimal proliferation following rat carotid injury. Methods: Antisense AT1B gene was transductedinto the carotid by adenoviral vector after carotid bal1oon injury and the restenosis model was established in SD rat.We measured neointima/media area ratio in local artery at day 21 after gene transfer. Results: Rat antisense AT1Bgene was successfully transducted into local carotid after the carotid balloon injury. Neointima/media area ratiowas significantly reduced (47 %, P<0. 01) at day 21 after gene transfer compared with the control group. Conclusion: The results suggest it is possible that antisense AT1B gene transfer as a potential therapeutic approach prevent neointimal hyperplasia.

Loss of cavin1 and expression of p-caveolin-1 in pulmonary hypertension: Possible role in neointima formation

BACKGROUND Pulmonary hypertension(PH) is a progressive disease with a high morbidity and mortality rate; and neointima formation leads to the irreversibility of the disease.We have previously reported that in rats, monocrotaline(MCT) injection leads to progressive disruption of endothelial cells(EC), and endothelial caveolin-1(cav-1) loss, accompanied by the activation of pro-proliferative pathways leading to PH. Four weeks post-MCT, extensive endothelial cav-1 loss is associated with increased cav-1 expression in smooth muscle cells(SMC). Exposing the MCTtreated rats to hypoxia hastens the disease process; and at 4 wk, neointimal lesions and occlusion of the small arteries are observed.AIM To identify the alterations that occur during the progression of PH that lead to neointima formation.METHODS Male Sprague-Dawley rats(150-175 g) were divided in 4 groups(n = 6-8 per group): controls(C); MCT(M, a single sc injection 40 mg/kg); Hypoxia(H,hypobaric hypoxia); MCT + hypoxia(M+H, MCT-injected rats subjected to hypobaric hypoxia starting on day1). Four weeks later, right ventricular systolic pressure(RVSP), right ventricular hypertrophy(RVH), lung histology, and cav-1 localization using immunofluorescence technique were analyzed. In addition, the expression of cav-1, tyrosine 14 phosphorylated cav-1(p-cav-1), caveolin-2(cav-2), cavin-1, vascular endothelial cadherin(VE-Cad) and p-ERK1/2 in the lungs were examined, and the results were compared with the controls.RESULTSSignificant PH and right ventricular hypertrophy were present in M and H groups [RVSP, mmHg, M 54±5~*, H 45±2~*, vs C 20±1, P < 0.05; RVH, RV/LV ratio M 0.57±0.02~*, H 0.50±0.03~*, vs C 0.23±0.007, P < 0.05]; with a further increase in M+H group [RVSP 69±9 mmHg, RV/LV 0.59±0.01 P < 0.05 vs M and H]. All experimental groups revealed medial hypertrophy; but only M+H group exhibited small occluded arteries and neointimal lesions. Immunofluorescence studies revealed endothelial cav-1 loss and increased cav-1 expression in SMC in M group; however, the total cav-1 level in the lungs remained low. In the M+H group, significant endothelial cav-1 loss was associated with increasing expression of cav-1 in SMC; resulting in near normalization of cav-1 levels in the lungs [cav-1, expressed as % control, C 100±0, M 22±4~*, H 96±7, M+H 77±6, ~* = P< 0.05 vs C]. The expression of p-cav-1 was observed in M and M+H groups [M314±4%, M+H 255±22% P < 0.05 vs C]. Significant loss of cav-2 [% control, C100±0, M 15±1.4~*, H 97±7, M+H 15±2~*; M and M+H vs C, ~* = P < 0.05], cavin-1 [%control, C 100±0, M 20±3~*, H 117±7, M+H 20±4~*; M and M+H vs C, P < 0.05] and VE-Cad [% control, C 100±0, M 17±4~*, H 96±9, M+H 8±3~*; M and M+H vs C, P <0.05] was present in M and M+H groups, confirming extensive disruption of EC.Hypoxia alone did not alter the expression of cav-1 or cav-1 related proteins.Expression of p-ERK1/2 was increased in all 3 PH groups [%control, C 100±0, M284±23~*, H 254±25~*, M+H 270±17~*; ~* = P < 0.05 vs C].CONCLUSION Both cavin-1 loss and p-cav-1 expression are known to facilitate cell migration;thus, these alterations may in part play a role in neointima formation in PH.

A Polymer Coated Cicaprost-Eluting Stent Increases Neointima Formation and Impairs Vessel Function in the Rabbit Iliac Artery

Drug-eluting stents have been successful in reducing in-stent restenosis but are not suitable for all lesion types and have been implicated in causing late stent thrombosis due to incomplete regeneration of the endothelial cell layer. In this study we implanted stents coated with cicaprost, a prostacyclin analogue with a long plasma half-life and antiproliferative effects on vascular smooth muscle cells, into the iliac arteries of rabbits. At 28-day follow-up we compared neointima formation within the stented vessels and vascular function in adjacent vessels, to assess if cicaprost could reduce restenosis without impairing vessel function. Arteries implanted with cicaprost eluting stents had significantly more neointima compared to bare metal stents. In adjacent segments of artery, endothelium-dependent relaxation was impaired by the cicaprost-eluting stent but vasodilation to an endothelium-independent vasodilator was maintained. We conclude that the presence of the polymer and sub-optimal release of cicaprost from the stent may be responsible for the increased neointma and impaired functional recovery of the endothelium observed. Further experiments should be aimed at optimising release of cicaprost and exploring different stent polymer coatings.

ROLE OF ENDOGENOUS CARBON MONOXIDE IN NEOINTIMAL FORMATION INDUCED BY BALLOON-INJURY IN RAT AORTA

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ROLE OF ANTISENSE AND DECOY OLIGONUCLEOTIDE OF NF-κB IN VESSEL STENOSIS AND NEOINTIMA FORMATION IN BALLOON-INJURED RAT ARTERY

Objective To examine antisense and decoy oligonucleotides of nuclear factor kappa B in vivo effects on intima proliferation and balloon-injured monocytes chemotactic protein-1 (MCP-1) and extracellular signal regulated kinase-2 (ERK2) expression in the carotid artery of rats. Methods Sprague-Dawley rats underwent balloon-dilation injury of the left carotid artery. Rats are divided into 7 groups (n=18) and each group includes 6 time points (6 h, 1, 3, 5, 7, 14 d) (n=3). Uninjured right carotid artery of the same rat was used as controls. Results In model group, sense group and scramble group, vessel intima area , media area and intima/media ratio increased after 5 d and reached the maximum after 7 d. The effect of antisense plus decoy group on intimal hyperplasia was more obvious than that of antisense group and decoy group alone. MCP-1 mRNA expression was increased expression continuously at 3, 5 and 7 d and decreased at 14 d. Compared with model group, sense group and scramble group, antisense group, decoy group and antisense plus decoy group had lowered MCP-1 mRNA expression in each time point (P<0.05). NF-κB p65 was dispersed positive stain 6 h after injury and increased after 1 d and peaked at 7 d, but the protein expression was weak at 14 d. ERK2 protein synthesis increased at 1 d and reached the peak at 7 d, while protein expression after 14 d was similar to that at 7 d. Treatment of antisense group, decoy group and antisense plus decoy group inhibited protein synthesis more significantly than those of model group, sense group and scramble group(P<0.05). Conclusion NF-κB modulates genes expression and protein synthesis of MCP-1 and ERK2. Celluar proliferation in vessel wall was dynamically changed after balloon angioplasty injury. Antisense and decoy oligonucleotide of NF-κB by local lipofectamine transfer inhibit NF-κB activating gene modulation and neointimal hyperplasia.

Neointimal coverage of sirolimus-eluting stents 6 months and 12 months after implantation： evaluation by optical coherence tomography

Optical coherence tomography （OCT） is a new imaging modality with resolution of approximately 10 pm and can be employed to visualize intracoronary characteristics. Sirolimus-eluting stents （SES） are susceptible to late thrombosis due to delayed reendothelialization over the stent struts, which may result in acute myocardial infarction or death. This study was designed to evaluate the re-endothelialization and neointimal coverage of SES with OCT 6 months and 12 months after implantation.Methods A total of 36 patients enrolled in the study underwent OCT examination 6 months （17 patients） and 12 months （19 patients） after SES implantation, The strut apposition to the vessel wall and neointimal coverage on SES struts were evaluated by OCT, Results Forty-six SES and 6561 struts were analyzed, At 6 months, 3041 struts （98.7%） were well-apposed and 39 struts （1,3%） were malapposed, At 12 months, 3434 struts （98,6%） were well-apposed and 47 struts （1,4%） were malapposed, Furthermore, only 4 SES at 6 months （18,2%） and 10 SES at 12 months （41,7%） were fully covered by neointimal growth, The average neointimal thicknesses covering the analyzed struts at 6 months and 12 months were （42±28） μm and （88±32） μm, respectively, There were 1989 struts at 6 months （72,1%） and 1461 struts at 12 months （45,6%） with neointimal thickness 〈100 μm, Conclusions OCT was able to visualize the strut apposition to the vessel wall and neointimal coverage on SES struts, At 6-month and 12-month follow-up examinations most struts were covered with thin neointima, but few of the entire SES showed full coverage. To prevent late-stent thrombosis in the presence of uncovered stent struts, longer dual antiplatelet drugs therapy should be recommended,

A Preliminary Study of the Therapeutic Role of Human Early Fetal Aorta-derived Endothelial Progenitor Cells in Inhibiting Carotid Artery Neointimal Hyperplasia

Background： Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells （EPCs） derived from human early fetal aortas in rat injured arteries. Methods： The carotid arterial endothelium of Sprague-Dawley rats was damaged by dilatation with a 1.5 F balloon catheter, and then EPCs derived from human early fetal aortas （〈14 weeks） were injected into the lumen of the injured artery in transplanted rats, with an equal volume of normal saline injected into control rats. Rats were sacrificed at 2 and 4 weeks after treatment and transplanted cells were identified by immunohistochemical staining with anti-human CD31 and anti-human mitochondria antibodies. Arterial cross-sections were analyzed by pathology, immunohistochemistry, and morphometry. Results： Green fluorescence-labeled EPCs could be seen in the endovascular surface of balloon-injured vessels after transplantation. The intimal area and intimal/medial area ratio were significantly smaller in the transplanted group than in the control （P 〈 0.05） and the residual lumen area was larger （P 〈 0.05）. After EPC transplantation, a complete vascular endothelial layer was formed, which was positive for human yon Willebrand factor after immunohistochemical staining, and immunohistochemical staining revealed many CD31- and mitochondria-positive cells in the re-endothelialized endothelium with EPC transplantation but not control treatment. Conclusion： EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury.

连接蛋白43与动脉粥样硬化的关系及干预策略的研究进展

动脉粥样硬化及机械性损伤所致新生内膜的形成机制极为复杂,随着研究的深入发现,连接蛋白43(Connexin 43)是血管细胞表达最为丰富的连接蛋白,其组成的半通道在血管病理变化的各个环节中发挥重要的调控作用。抑制Connexin 43表达活性为动脉粥样硬化的治疗提供新的策略与潜在治疗靶点。本文聚焦于Connexin43与动脉粥样硬化关系的最新研究进行综述。

4种肺动脉高压动物模型肺血管重构模式的差异研究

目的:探讨4种肺动脉高压(PH)动物模型肺血管重构模式的差异。方法:雄性SD大鼠(350-400g),分别通过腹主动脉-腔静脉分流(A-VF,n=10)、左肺切除(PE,n=10)、野百合碱注射(MCT,n=10)、左肺切除+MCT(PE+MCT,n=12)4种方法建立PH模型。检测平均肺动脉压力(mPAP)、RV/(LV+S)重量比值、肺小动脉中膜厚度百分比(WT%)、无肌性动脉肌化程度和新生内膜(neointima)形成、新生内膜增殖度和血管阻塞计分(VOS)。结果:在PE+MCT组(肺切除术后5周,MCT注射后4周)右肺腺泡内血管出现了新生内膜病变,其它组均没有新生内膜病变形成。PE+MCT组的动物出现了严重的右心室肥大,动脉中膜明显增厚,平均肺动脉压(mPAP)和无肌性血管肌化程度显著增加;A-VF、PE和MCT组仅形成轻-中度的右心室肥大、mPAP升高和小动脉肌化。结论:左肺切除联合应用MCT能成功诱导大鼠PH新生内膜模型,该模型能更好地模拟人类严重PH的病理改变,是研究梗阻性PH更为适用的动物模型。

硅胶管包裹大鼠颈动脉对血管收缩功能的影响

目的观察硅胶管包裹所致的血管外膜损伤对大鼠颈动脉收缩功能的影响。方法用硅胶管经血管外膜包裹大鼠颈动脉,分别于术后3 d、1周、2周测量大鼠双侧颈动脉血流量,观察血管对局部应用5-羟色胺(5-HT)的反应,光镜下观察血管形态学变化。结果与对照侧比较,硅胶管包裹大鼠颈动脉的早期阶段,包管侧颈动脉呈血管慢性收缩的组织学改变,表现为血管腔缩小[包管3 d缩小(12.15±2.29)%(P=0.003);包管1周缩小(45.17±3.84)%(P<0.001)]。内弹力板弯曲、中膜增厚[包管3 d增厚(23.04±5.96)%(P=0.009);包管1周增厚(61.65±10.32)%(P<0.001)],伴颈动脉血流量降低及血管对5-HT的收缩反应增强。硅胶管包裹2周,包管侧颈动脉管壁重塑,表现为中膜增厚[增厚(31.52±4.56)%(P=0.012)]及弥漫性血管内膜增生[新生内膜面积平均(0.19±0.05)mm2],伴血管腔面积缩小[减少(37.17±4.57)%(P<0.001)]及颈动脉血流量降低,血管对5-HT的收缩反应恢复至对照侧水平。结论血管外膜损伤能引起血管收缩功能增强及新生内膜形成,血管收缩功能的改变出现在内膜增生性病变之前。

镁合金血管支架置入后内膜增生特点

目的观察和评价AZ31镁合金血管支架置入后的内膜增生情况。方法将24枚采用激光雕刻制成的AZ31镁合金支架置入12只Beagle犬的双侧髂外动脉内,按支架置入术后时间将动物分为1、3、6个月三组,每组4只。在相应时间点取支架段血管进行HE染色,观察镁合金支架置入后内膜增厚程度、新生内膜成分及形态特点。结果 AZ31镁合金支架置入术后1、3、6个月均产生了较明显的内膜增生,内膜-中膜比值分别为1.17±0.06、1.64±0.09、0.91±0.05,相比1个月和6个月,术后3个月时内膜增生最为明显(P<0.05),且内膜增厚以支架支撑杆周围为著,新生内膜主要成分为排列紊乱的血管平滑肌细胞及细胞外基质,在置入术后早期可见少量的炎性细胞。结论虽然AZ31镁合金血管支架具有可降解性,但其置入后仍出现不同程度内膜增生,且以3个月时最为明显。

光学相干断层成像评价国产新型药物洗脱支架术后内膜增殖

目的应用光学相干断层成像技术评价新型国产冠状动脉雷帕霉素药物洗脱支架(BUMA)置入后内膜覆盖。方法入选22例冠状动脉造影提示为原发冠状动脉病变需置入支架的冠心病患者,随机分为BUMA组(n=15)和对照组Endeavor组(n=7),术后9个月行光学相干断层成像检查。结果 BUMA组平均内膜增殖厚度显著小于Endeavor组(0.220±0.140mm对0.269±0.207mm,P<0.001);BUMA组无内膜覆盖百分率显著低于Endeavor组(5.65%对6.56%,P<0.001);BUMA组支架内管腔面积丢失显著小于Endeavor组有统计学差异[(34.87±11.50)%对(40.82±18.53)%,P=0.025]。结论冠心病患者置入国产新型BUMA药物洗脱支架具有良好的安全性和有效性。

重组人白介素-10抑制晚期糖基化终产物诱导的大鼠血管平滑肌细胞和血管新生内膜的增殖(英文)

研究观察了重组人白介素 10 (rhIL 10 )对晚期糖基化终产物 (AGE)刺激下离体大鼠胸主动脉血管平滑肌细胞增殖及对SD大鼠血管损伤后新生内膜增殖的影响。体外培养大鼠主动脉血管平滑肌细胞 ,采用MTS/PES法确定血管平滑肌细胞的增殖状态 ;应用流式细胞术测定细胞周期 ;利用 p44 / 42磷酸化抗MAPK抗体的蛋白免疫印迹法测定 p44 / 42MAPK磷酸化蛋白表达。利用大鼠颈动脉血管损伤模型 ,观察rhIL 10对新生内膜增殖的影响。结果显示 :( 1)AGE处理组与对照组相比 ,AGE对血管平滑肌细胞增殖具有明显的刺激作用 (P <0 0 5 )。rhIL 10单独应用对血管平滑肌细胞生长没有影响 (P >0 0 5 )。在AGE刺激下 ,低至 10 0ng/ml的rhIL 10可抑制血管平滑肌细胞的生长 (P <0 0 5 )。( 2 )流式细胞术测定的结果显示 ,rhIL 10可以使AGE作用下的VSMC大部分处于G0 /G1期 ,与对照组相比有明显差异 (P <0 0 1)。 ( 3 )AGE对 p44 / p42MAPK磷酸化蛋白表达有显著的增强作用 ,此作用可被rhIL 10抑制 (P <0 0 0 1)。( 4)大鼠颈动脉损伤后 ,rhIL 10治疗组的动脉血管新生内膜 /中层面积比低于对照组约45 % (P <0 0 1)。表明抗炎细胞因子rhIL

冠状动脉支架内再狭窄发生机制的研究进展

经皮冠状动脉介入术是目前治疗冠状动脉粥样硬化性心脏病的主要有效的治疗手段,血管支架尤其是药物洗脱支架极大程度上改善了冠心病患者的疗效和预后。与支架相关的病理主要表现为支架内再狭窄引起的进行性心绞痛和支架内血栓导致的急性心肌梗死。支架内再狭窄是由生物、机械、技术及与患者自身相关的复杂相互作用介导形成的病理性新生内膜增生,有关其发病机制的研究正不断深入。本文通过血管内皮损伤、血管平滑肌细胞增殖迁移、血管外基质重构、炎症反应以及新生动脉内膜粥样硬化等方面对其进行综述,深入探讨其形成的影响因素及临床意义。

自体内皮细胞移植在损伤动脉再内皮化及抑制新生内膜增生中的作用

目的 :观察自体内皮细胞移植在损伤动脉血管再内皮化及抑制新生内膜增生中的作用。方法 :30只健康雄性纯种新西兰兔行双侧髂股动脉球囊损伤 ,一侧于损伤后立即经球囊导管行自体静脉内皮细胞移植 ,另一侧行培养基对照。其中 10只动物分别于术后 4h、4d处死 ,行扫描电镜检查 ;5只动物 ,先将细胞用荧光标记物标记后 ,再移植入体内 ,4d后进行荧光示踪检查 ;5只动物于术后 4d行Evansblue染色 ,观察内皮损伤血管段再内皮化情况 ;其余动物于术后 2 8d处死 ,行病理学分析。结果 :细胞移植术后 4h ,对照组见整个内皮层剥脱 ,暴露出内皮下弹力膜及平滑肌 ,细胞移植组则见部分移植内皮已粘附在内皮剥脱血管壁 ,细胞呈圆形 ,但尚未铺展 ;细胞移植术后 4d ,移植的内皮已变形 ,在内皮剥脱血管壁铺展成单层 ,大量荧光标记内皮细胞被覆在损伤动脉血管内膜 ;对照组损伤血管几乎完全被Evansblue染成蓝色 ,细胞移植组损伤血管则 6 0 %不被Evansblue着染 ;病理学分析发现细胞移植组新生内膜面积、最大动脉内膜厚度均显著少于对照组。结论 :自体内皮细胞能有效地经球囊导管移植到内皮损伤血管段 ,并有减轻新生内膜增生的作用。

聚合物涂层改性对药物洗脱支架植入后血管内膜修复的作用

目的研究雷帕霉素洗脱支架聚合物涂层改性促进血管内皮化及抑制内膜增殖的作用。方法选择32只小型猪,在冠状动脉内随机植入裸支架(BMS)15枚、新型聚合物涂层支架(Polymer)17枚、FireBird2雷帕霉素洗脱支架(SES-FB2)17枚和新型聚合物涂层的雷帕霉素洗脱支架(SES-Plus)15枚,分别于植入后7、28 d取材,用扫描电镜分析内皮化程度,并分别于28、180 d取材,病理分析内膜增生程度。结果扫描电镜分析显示,与SES-FB2组相比,支架植入后7 d和28 d,SES-Plus组内皮覆盖率显著增加(分别为23%±11%比47%±21%和84±21%比100%,P<0.05),而BMS、Polymer和SES-Plus三组之间差异无统计学意义(P>0.05)。病理分析显示,支架植入后28 d和180 d,SES-Plus组和SES-FB2组间的新生内膜面积差异无统计学意义[分别为(2.28±0.84)mm^2比(2.08±0.76)mm^2和(3.19±0.63)mm^2比(3.06±1.33)mm^2,P>0.05]。结论 SES-Plus能有效抑制内膜增生,具有明显的促进内皮化作用。

血管内放射抑制猪冠状动脉球囊损伤后新生内膜形成及血管重塑

目的：观察血管内放射治疗再狭窄的有效性及相关问题，并进一步应用于临床。方法：小型猪１２ 头，体重２０ ～３０ ｋｇ 。实验组（ ｎ ＝ ７） ，在动物麻醉后，切开右股动脉，插入动脉鞘管，对冠状动脉前降支和（ 或） 回旋支的近中段进行球囊扩张术，保留０－０１４″的导丝，插入４ Ｆ ＵＳＣＩＰｒｏｂｉｎｇ Ｃａｔｈｅｔｅｒ ，并覆盖目标血管段，将带有１９２Ｉｒ 线源（ 活性长度３０ｍ ｍ ，直径０－５ ｍ ｍ ，放射活度在３５０ ～４１９ ｍＣｉ） 的导丝（ 长２８０ ｍ ｍ ，直径０－８９ ｍ ｍ） 定位在目标血管段，进行血管内放射治疗（２０ Ｇｙ） 。对照组（ ｎ ＝ ５） ，未进行治疗。术后３０ 天处死动物，快速取心脏，用中性福尔马林对冠状动脉进行原位灌注，切片行苏木素伊红、马宋三色和维尔霍夫范吉狲染色，计算机图像分析系统分析形态学及组织学的变化。结果：１ 个月后损伤处内弹力膜断裂、中膜撕裂，并有内膜增殖及管腔狭窄。放射治疗后３０ 天明显减少了血管内膜厚度（６７－３ ％ ，Ｐ＜ ０－０１） 、新生内膜面积（６７－６ ％ ，Ｐ＜ ０－０１） 和狭窄面积百分比［ 对照组：（４４－７ ±２０－７） ％ ， 实验组：（１６－６ ±１１－５） ％ ，Ｐ ＜０－０１］ ?

大鼠自体内瘘模型制备及内瘘狭窄的实验研究

目的吻合口内膜增生可导致自体动静脉内瘘失功,本研究拟在设计大鼠模型研究其进程及机制。方法SPF 级wistar 大鼠,行右颈总动脉-颈内静脉端端吻合,术后14,28 天处死,取近吻合口静脉、动脉组织,行 HE 染色,弹力、胶原纤维的双重组合染色,PCNA、TGF- β 1、NF- κ B 免疫组化。结果内瘘吻合术后 14 天近吻合口静脉端见明显的内膜增生,呈息肉样增生,其中平滑肌细胞增生活跃,大量胶原纤维沉积,28 天管腔明显狭窄。特殊染色见术后 14、28 天近吻合口静脉内弹力层不连续。PCNA、NF- κB在近吻合口静脉壁中膜和外膜高表达,在14 天达到一个高峰,在28 天观察期内仍持续高表达。TGF- β1 在外膜基质高表达。结论大鼠右侧颈总动脉-颈内静脉端端吻合可模拟内瘘局部血流动力学的影响,短期内可见明显内膜增生等病理表现,是一种合适的自体动静脉内瘘动物模型,显示TGF- β1,NF- κB参与了内瘘内膜增生病理过程。