内源性一氧化碳对大鼠主动脉球囊损伤后新生内膜形成及丝裂素活化蛋白激酶活性的影响

目的：探讨内源性血红素加氧酶（ｈｅｍｅｏｘｙｇｅｎａｓｅ,ＨＯ）／ 一氧化碳（ｃａｒｂｏｎ ｍｏｎｏｘｉｄｅ,ＣＯ） 系统对大鼠主动脉球囊损伤后新生内膜形成及丝裂素活化蛋白激酶（ｍｉｔｏｇｅｎａｃｔｉｖａｔｅｄ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ, ＭＡＰＫ） 激活的调节作用。方法：采用大鼠主动脉内膜球囊拉伤模型,观察ＨＯ 抑制剂锌卟啉９（ｚｉｎｃ ｐｒｏｔｏｐｏｒｐｈｙｒｉｎＩＸ,ＺｎＰＰ９）或其底物血红素左旋赖氨酸盐（ｈｅｍｅＬｌｙｓｉｎａｔｅ,ＨＬＬ）对血管壁细胞３ＨＴｄＲ掺入和ＭＡＰＫ 活性的影响,同时观察血管平滑肌ＨＯ活性和ＣＯ 生成的变化。结果：内膜拉伤后２ 周血管３ＨＴｄＲ 掺入和ＭＡＰＫ 活性明显增加,同时ＨＯ 活性和ＣＯ 的产生增加;ＺｎＰＰ９ 使血管的３ＨＴｄＲ掺入和ＭＡＰＫ 活性增加更为明显（ 分别比单独拉伤组增加３４ ．６％ 和３９．２％ ,均为Ｐ＜ ０．０１） ;而ＨＬＬ 使血管的３ＨＴｄＲ 掺入和ＭＡＰＫ 活性则明显降低（ 比单独拉伤组分别减少２９．４５ ％ 和３３．６ ％ ,均为Ｐ＜ ０．０１） 。结论：ＨＯ 活性上调或ＣＯ 产生增加是血管对机械拉伤的一种保护性应激反应;内源性ＨＯ／ＣＯ 系统直接     

腺病毒介导的TIMP-4基因转染抑制血管损伤后新生内膜形成

目的 :应用腺病毒介导的转基因方式转染人组织型金属蛋白酶抑制剂 4 (TIMP 4 )基因 ,以观察TIMP 4对球囊损伤后新生内膜形成的影响。方法 :体外培养血管平滑肌细胞 (VSMC)并转染含有TIMP 4基因的重组复制缺陷型腺病毒载体 (AdTIMP 4 ) ,采用单层培养细胞刮片法 ,观察TIMP 4对细胞迁移的影响 ;以大鼠颈总动脉球囊损伤模型为研究对象 ,损伤后即刻经血管外膜分别转入盐水、空载腺病毒载体和含有TIMP 4基因的腺病毒载体 ,观察细胞迁移和新生内膜形成情况。结果 :培养的VSMC转染AdTIMP 4后 ,细胞迁移明显受到抑制 ,与对照组相比抑制率为 6 3.9% (P <0 .0 1) ;在大鼠颈总动脉球囊损伤模型中 ,转基因后 4d时生理盐水组、空载腺病毒组和转染AdTIMP 4组内弹力板内的细胞数依次为 (32 .5± 4 .8)个细胞、(33.8± 7.0 )个细胞和 (8.2± 2 .4 )个细胞 ,转染TIMP 4可以显著抑制血管损伤后细胞向内膜的迁移 ;血管损伤后 2 8d时 ,转染TIMP 4组新生内膜面积与中膜面积比值与对照组相比降低了 6 6 .5 % (P <0 .0 1) ,空载腺病毒组与生理盐水组之间差异无显著性。结论 :TIMP 4可以抑制培养的VSMC的迁移 ,局部干预可以明显抑制大鼠颈总动脉球囊损伤后细胞的迁移和血管新生内膜的形成。     

大鼠胸主动脉球囊成形术后血管壁丝裂素活化蛋白激酶活性的变化

目的；丝裂素活化蛋白激酶（MAPK）与大鼠胸主动脉内皮剥脱术后平滑肌细胞（SMC）增殖的关系。方法：将剥脱术后的Wistar大鼠随机分为两组（n＝6），分别于术后7天和14天时处死取材，其血管条分别做3H－TdR参入和MAPK活性测定，并与假手术组相比较。结果：剥脱术后7天和 14天与假手术组相比，3H－TdR参入分别是后者的 2.6倍和 2． 0倍（P＜0. 01），MAPK活性分别为 7.6倍和 2. 4倍（P＜0．01）。结论：大鼠胸主动脉球囊内皮剥脱术后血管SMC发生增殖，同时MAPK活性明显升高，说明MAPK与内皮损伤后的血管壁SMC增殖有关。     

氯沙坦对血管内皮损伤后血小板活化及AngⅡAT1受体表达的影响吴逸南

目的：研究球囊损伤血管后内膜增生的过程、血小板活化水平、血管紧张素ⅡAT1受体mRNA的变化及氯沙坦对其的影响。方法：随机将72只雄性Wistar大鼠分为对照组、手术组和氯沙坦治疗组，每组24只。分别在术后3、7、14和28d，采用组织学检查、放射免疫法和RT PCR技术检测内膜增生的情况、血小板表面GMP 140的数量、AT1受体mRNA的水平及氯沙坦(30?mg•kg-1•d-1)灌胃对其的影响。结果：① AT1受体mRNA于术后3?d明显增高(P<0.05)，并持续至术后14?d（P<0.01）；② GMP 140于术后3?d明显升高，术后7?d开始下降（P<0.01）；③ 内皮损伤术后3?d已有增殖的血管平滑肌细胞(VSMC)移行至内膜层，7?d内膜开始增生，14?d　VSMC的增殖及内膜增生更为明显，28?d　VSMC的增殖明显减弱，细胞外基质增加，内膜继续增生；④ 应用氯沙坦后AT1受体mRNA表达增加（P<0.05, P<0.01），但血小板表面GMP 140的数量和VSMC的移行、增殖减弱，内膜增生程度减轻（P<0.05, P<0.01）。结论：血管内皮损伤后内膜增生的过程中血小板活化、AT1受体mRNA表达增加，氯沙坦能抑制血小板的活化及VSMC的移行、增殖，减轻内膜增生的程度，上调AT1受体mRNA的表达。     

内皮剥脱后血管平滑肌增生的时相特征

观察了内皮损伤后血管平滑肌细胞（ＶＳＭＣ）增生的时相变化。结果表明，内皮损伤可导致ＶＳＭＣ增生，内膜增厚。ＶＳＭＣ在术后２４小时就进入细胞周期，开始合成ＤＮＡ；ＤＮＡ复制高峰是在术后４８～７２小时，１０天之后主要是细胞体积增大，细胞外基质堆积，提示细胞的大量复制是在内皮损伤后的早期阶段，这可能是防治的关键时期。     

雄激素对损伤的血管内皮细胞功能的影响

目的 :观察雄激素对球囊损伤的血管内皮细胞功能的影响。方法 :12只雄性家兔随机等分为替代组和单纯去势组 ,均于去势术后 2周行右侧髂动脉内皮剥脱术 ,替代组同时给予十一酸睾酮。观察去势前、脱内皮术后1周、2周血浆一氧化氮 (NO)、内皮素 1(ET 1)水平的变化 ;脱内皮术后 2周将动物处死 ,取损伤血管段 ,应用免疫组织化学法观察血管细胞粘附分子 1(VCAM 1)的表达和应用HE染色观察血管病理形态的变化。结果 :与单纯去势组相比 ,替代组脱内皮术后 1周、2周血浆NO水平 (μmol L)明显降低 [1周时 :(46 .70± 12 .6 5 )vs(75 .6 2± 16 .0 4 ) ,2周时 :(6 5 .0 3± 16 .2 9)vs(12 5 .4 9± 2 2 .4 5 ) ,P均 <0 .0 1];血浆ET 1水平 (pg ml)明显升高 [1周时 :(14 5 .2 1± 11.4 0 )vs(118.6 6± 12 .82 ) ,2周时 :(111.16± 13.0 1)vs(81.2 8± 7.80 ) ,P <0 .0 0 1或 0 .0 1];脱内皮术后 2周损伤血管组织VCAM 1表达明显增强 [(0 .346 5± 0 .0 0 84 )vs(0 .310 9± 0 .0 0 5 6 ) ,P <0 .0 0 1];损伤血管内膜面积 (mm2 )和内膜 中膜面积比值明显增大 [(1.6 5± 0 .39)vs(0 .6 5± 0 .18) ,(0 .92± 0 .2 0 )vs(0 .38± 0 .0 7) ,P均 <0 .0 1]。结论 :雄性兔去势后补充该实验剂量的睾酮使血清睾酮水平升高可?     

Effects of granulocyte colony-stimulating factor on repair of injured canine arteries

Background Endothelial progenitor cells （EPCs） derived from bone marrow may differentiate into endothelial cells and participate in endothelial repair. These cells can be mobilized into peripheral blood by cytokines, including granulocyte colony-stimulating factor （G-CSF）. In the present study, we investigated the effects of G-CSF on neointimal formation and restenosis in a canine model of arterial balloon injury.
Methods Sixteen male beagle dogs were injected subcutaneously with 20 μg·kg^-1·d^-1 recombinant human G-CSF （n=8） or normal saline （n=8） for 1 week. On the fifth day of treatment, the dogs underwent renal arterial angioplasty. At 8 weeks after arterial balloon injury, angiographic observations were made and injured arteries were processed for morphometric analysis of neointimal formation.
Results Peripheral white blood cell counts were increased by 3.34-fold compared to baseline on the fifth day of administration of G-CSF. Angiographies revealed that one stenosis had occurred among the eight injured renal arteries from dogs treated with G-CSF, whereas all injured renal arteries from dogs treated with normal saline remained patent. The mean extent of stenosis among injured arteries was 18.3%±17.9% in the G-CSF treated group compared to 12.5%±7.6% in the saline treated control group （P=0.10）. G-CSF treatment slightly increased neointimal thickness （0.42±0.15 mm vs 0.25±0.06 mm, P=-0.08） with an intima to media ratio of 0.83±0.49 vs 0.54±0.18 （P=0.11）.
Conclusions G-CSF treatment does not attenuate neointimal hyperplasia and restenosis formation in a canine model of renal arterial injury, suggesting that the therapeutic strategy for preventing restenosis by stem cell mobilization should be investigated further.     

内源性一氧化碳与一氧化氮在高血压发病中的相互作用

目的：研究一氧化氮合酶（ｎｉｔｒｉｃ ｏｘｉｄｅ ｓｙｎｔｈａｓｅ, ＮＯＳ）／一氧化氮（ｎｉｃｔｒｉｃ ｏｘｉｄｅ, ＮＯ） 系统和血红素加氧酶（ｈｅｍｅ ｏｘｙｇｅｎａｓｅ,ＨＯ）／一氧化碳（ｃａｒｂｏｎ ｍｏｎｏｘｉｄｅ,ＣＯ）系统在高血压发生机制中的作用及其相互关系。方法：采用ＮＯＳ抑制剂诱导大鼠高血压模型,观察大鼠动脉血压,主动脉组织ＮＯＳ、ＨＯ 活性和ＣＯ 产生释放的变化。结果：大鼠在注射ＮＯＳ抑制剂———左旋硝基精氨酸（ＮＧｎｉｔｒｉｃＬａｒｇｉｎｉｎｅ, ＬＮＮＡ）后第４ 周血压明显增高,同时ＨＯ活性和ＨｂＣＯ形成分别增加２８ ．４％ 和３１ ．１ ％ （ 均为Ｐ＜ ０ ．０１）,血浆和主动脉平滑肌ｃＧＭＰ含量明显增加。同时注射ＨＯ 底物ＨＬＬ和ＬＮＮＡ时,４ 周内血压无明显改变,而ＨＯ活性、ＨｂＣＯ的形成、血浆和主动脉平滑肌ｃＧＭＰ含量比单纯ＬＮＮＡ组增加更明显。结果表明在ＮＯＳ抑制剂诱导的大鼠高血压形成过程中,内源性ＨＯ／ＣＯ 系统可呈代偿性上调状态;应用ＨＯ 底物可诱导ＨＯ活性和ＣＯ 的生成增加,对ＮＯＳ抑制剂所诱导的高血压有防止作用。结论：内源性ＣＯ和ＮＯ都参与血管张力的调节,两者在高血压发生发展     

INHIBITORY EFFECT OF FLUVASTATIN ON AORTIC INTIMAL THICKENING IN NORMOCHOLESTEROLEMIC RABBITS

Objective, The anti-atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter-induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods. Fifty-six rabbits were randomly divided into eight groups( n = 7, each). Fluvastatin was given mixed with food at daily dose of 8mg/kg starting 5 days before catheterization. Light microscope, immanohistochemistry, transmis-sion electron microscope and RT-PCR assay were applied to assess vascular smooth muscle cell (VSMC) proliferation and apoptosis, as well as oncogene expression in vascular wall. Results. At day 10 and day 15 after catheter induced denudation intima/media( I/M) thickness ratio was obviously higher, and also the percentage of PCNA-positive cells and TUNEL-positive cells in media was significantly higher compared with controls. The intimal hyperplasia was mostly composed of α-SM-actin-pesitive cells. In rabbits given flu-vastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvas-tatin.The overexpression of proto-oncogene H-ras mRNA and decreased expression of anti-oncogene p53 mRNA were found after vascular injury, whereas fluvastatin significantly reduced H-ras mRNA and increased p53 mRNA expres-sion. Conclusion. Proliferation of VSMC in the media and the migration to the intima can be inhibited, and apoptosis of VSMC be induced by short-term use of fluvastatin after balloon catheter denudation, independent of serum lipid change. The underlying mechanism is presumably associated With the influence of fluvastatin on oncogene expression in the injured vascular Wall.     

C-型利钠利尿肽在球囊血管损伤中的作用

目的：在大鼠主动脉球囊剥脱模型上观察血浆和主动脉组织Ｃ型利钠利尿肽（Ｃｔｙｐｅ ｎａｔｒｉｕｒｅｔｉｃ ｐｅｐｔｉｄｅ,ＣＮＰ）的质量浓度和ｍＲＮＡ 表达的动态变化及外源性ＣＮＰ对大鼠球囊损伤后内膜生成的影响,以探讨ＣＮＰ在再狭窄中的作用。方法：放射免疫法测定ＣＮＰ质量浓度,ＲＴＰＣＲ 测定ＣＮＰｍＲＮＡ 的表达。结果：发现大鼠球囊损伤后血浆ＣＮＰ的质量浓度升高, 内膜剥脱后第３ 天、１０ 天、２１ 天,血浆ＣＮＰ 水平分别增高８０ ．７％ （ Ｐ＜ ０．０１） ,４３．５ ％ （Ｐ＜ ０．０５） 和２７ ．５％ （Ｐ＜ ０．０５）,而主动脉组织ＣＮＰ含量在损伤后第３ 天下降４６ ．６％ （Ｐ＜ ０．０５） ,第１０ 天,２１ 天和２８ 天ＣＮＰ含量分别增加２ ．８ 倍（ Ｐ＜ ０ ．０１） 、１．６ 倍（ Ｐ＜ ０ ．０５） 和０ ．８２ 倍（Ｐ＜ ０．０５）。在血管损伤３ 天时ＣＮＰｍＲＮＡ 的表达减弱,而第１０ 天和第２１ 天ＣＮＰｍＲＮＡ 的表达明显增强。外源性ＣＮＰ显著抑制球囊损伤后第７ 天和２１ 天新生内膜的形成,内膜／中膜比值分别降低２３％ （Ｐ＜ ０．０５）和２０ ％ （Ｐ＜０ ．０５）。结论：ＣＮＰ参与血管球囊损伤后的修复过程,可能是机体     

EFFECTS OF CERTAIN VASOACTIVE PEPTIDES ON PATHOGENESIS OF VASCULAR RESTENOSIS

Objective. To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty.Methods. In rat aortic artery restenosis model produced by denudation of aortic endothelia, we observed changes of endothelin (ET), angiotensin II (AII), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in plasma and aorta with radioimmunoassay and expression of hypertension-related gene (HRG-1) with semi-quantitative RT-PCR, and studied the effects of these peptides on intimal hyperplasia, intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore, in cultured cells, we studied the effects of these peptides on vascular smooth muscle cell (VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with 3H-TdR incorporation and RT-PCR respectively.Results. After angioplasty, the levels of ET and AII in plasma and aorta significantly increased, accompan     

ENDOGENOUS HEME OXYGENASE/CARBON MONOXIDE SYSTEM MEDIATES LIPOPOLYSACCHARIDE-INDUCED INTUSSUSCEPTION IN RATS

ＩＮＴＲＯＤＵＣＴＩＯＮ　　Ｉｎｔｕｓｓｕｓｃｅｐｔｉｏｎ(ＩＮ)ｉｓｏｎｅｏｆｔｈｅｃｏｍｍｏｎｅｓｔａｂｄｏｍｉｎａｌｅｍｅｒｇｅｎｃｉｅｓｉｎｐｅｄｉａｔｒｉｃｓｕｒｇｅｒｙ .Ｔｈｅｃｏｍｐｒｅｓｓｉｏｎａｎｄａｎ ｇｕｌａｔｉｏｎｏｆｔｈｅｍｅｓｅｎｔｅｒｉｃｂｌｏｏｄｖｅｓｓｅｌｓｏｆｔｈｅｉｎｖａｇｉｎａｔｅｄｂｏｗｅｌａｎｄｔｈｅｐｒｅｓｓｕｒｅｏｎｔｈｅｂｏｗｅｌｗａｌｌｃａｎｌｅａｄｔｏｎｅｃｒｏ ｓｉｓａｎｄｐｅｒｆｏｒａｔｉｏｎ .Ｔｈｅｉｎｃｉｄｅｎｃｅｉｓ 2 4ｐｅｒ 10 0 0ｌ…     

ENDOGENOUS HEME OXYGENASE/CARBON MONOXIDE SYSTEM MEDIATES LIPOPOLYSACCHARIDE－INDUCED INTUSSUSCEPTION IN RATS

Objectives. To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats.Methods. IN model of rats were induced by lipopolysaccharide. HO activity was determined by the amount of bilirubin formation which was measured with a double-beam spectrophotometer, and HbCO formation was measured by CO-oximeter.Results. The results showed that LPS (10mg/kg) caused IN in up to 40% of the rats at 6h after treatment of LPS. The incidence of IN were significantly increased by 50% (P＜0.05) and by 83.2%(P＜0.01) in HO substrate(heme-L-lysinate)-treated rats and in exogenous CO-treated rats, respectively; but it was significantly decreased by 41.8%(P＜0.05) after administration of ZnDPBG, an inhibitor of heme oxygenase (HO) activity. Furthermore, LPS increased HO activity, HbCO formation cGMP content within colic smooth muscle and the plasma level of cGMP, and these parameters were significantly elevated by 62.6%(P＜0.01), 40.0%(P＜0.01), 49.3%(P＜0.05) and 38.9%(P＜0.05), respectively, compared with LPS-non-IN rats.Conclusion. It is suggested that endogenous HO/CO system plays an important role in the process of IN induced by LPS, and inhibition of HO activity may decrease the formation of IN.     

科素亚、强的松对兔颈总动脉内皮剥脱后内膜中膜增生的影响

目的观察家兔颈总动脉内皮剥脱后,单用血管紧张素Ⅱ的I型受体拮抗剂科素亚和加用强的松,对内皮、血管平滑肌细胞过度增生的抑制作用。方法纯种新西兰白兔30只,随机分3组。采用颈总动脉球囊内皮剥脱术,制造内皮损伤、平滑肌过度增生模型。Ⅰ组为对照组,Ⅱ组术后给予科素亚,山组术后1～5d内服用科素亚的同时加用强的松。采用光镜、电镜观察,并将结果做统计学处理。结果急性期内皮炎性反应Ⅲ组较Ⅰ组、Ⅱ组明显减轻,14～28d内膜中膜平滑肌细胞增生Ⅱ组、Ⅲ组较l组显著降低,Ⅲ组降低更明显。Ⅱ组、Ⅲ组内膜中膜厚度与Ⅰ组比较有显著性差异,但Ⅱ组与Ⅲ组比较差异无统计学意义。结论科素亚能抑制家兔颈总动脉球囊内皮剥脱后的平滑肌细胞增生,急性期加用强的松降低内皮对损伤的反应程度,可增强科素亚对血管平滑肌细胞增生的抑制作用,达到降低内皮损伤后IMT增厚的疗效,为防治血管成形术后再狭窄,降低卒中发生率提供动物实验资料。     

ENDOGENOUS HEME OXYGENASE／CARBON MONOXIDE SYSTEM MEDIATES LIPOPOLYSACCHARIDE- INDUCED INTUSSUSCEPTION IN RATS

Objectives. To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats.Methods. IN model of rats were induced by lipopolysaccharide. HO activity was determined by the amount of bilirubin formation which was measured with a double-beam spectrophotometer, and HbCO formation was measured by CO-oximeter.Results. The results showed that LPS (10mg/kg) caused IN in up to 40% of the rats at 6h after treatment of LPS. The incidence of IN were significantly increased by 50% (P＜0.05) and by 83.2%(P＜0.01) in HO substrate(heme-L-lysinate)-treated rats and in exogenous CO-treated rats, respectively; but it was significantly decreased by 41.8%(P＜0.05) after administration of ZnDPBG, an inhibitor of heme oxygenase (HO) activity. Furthermore, LPS increased HO activity, HbCO formation cGMP content within colic smooth muscle and the plasma level of cGMP, and these parameters were significantly elevated by 62.6%(P＜0.01), 40.0%(P＜0.01), 49.3%(P＜0.05) and 38.9%(P＜0.05), respectively, compared with LPS-non-IN rats.Conclusion. It is suggested that endogenous HO/CO system plays an important role in the process of IN induced by LPS, and inhibition of HO activity may decrease the formation of IN.     

全反式维甲酸对大鼠腹主动脉球囊损伤后血管重塑的影响

目的:研究全反式维甲酸(ATRA)对球囊损伤大鼠腹主动脉血管重塑的影响。方法:制作球囊损伤的大鼠腹主动脉剥脱模型,12只Wistar大鼠随机分为①对照组:6只腹腔内注射intralipid(1mL/d),②ATRA组:6只腹腔内注射溶解于intralipid的ATRA(4mg·kg~(-1)·d~(-1)).球囊损伤14d后,损伤区域的血管段用10％福尔马林固定,然后染色,进行形态学分析。结果:ATRA明显减小新生内膜面积(IA),增加管腔面积(LA)和外弹力膜包绕面积(EEL)。结论:ATRA具有促进有益的血管重塑的作用。     

血管活性肽在大鼠血管再狭窄形成中的作用

目的 研究血管活性肽在血管再狭窄形成中的作用。方法 在大鼠主动脉内皮球囊拉伤模型上,采用放射免疫法测定大鼠血浆及主动脉组织内皮素（ＥＴ）、降钙素基因相关肽（ＣＧＲＰ）和肾上腺髓质素（Ａdm）含量以及组织中血管紧张素Ⅱ（ＡⅡ）含量,用∧３Ｈ－ＴdＲ掺入法和组织学分析观察血管平滑肌细胞（ＶＳＭＣ）增生以及血管内膜／中膜面积比值。并在培养的ＶＳＭＣ上,采用∧３Ｈ－ＴdＲ掺入法研研究血管活性肽对细胞增生的影响。采用ＲＴ－ＰＣＲ法观察血管活性肽对自发性高血压大鼠（ＳＨＲ）和ＷＫＹ大鼠的主动脉和ＶＳＭＣ高血压相关基因－１（ＨＲＧ－１）表达的影响。结果 术后１０d ,血浆及主动脉ＥＴ达高峰,分别较对照组升高６９％和1２４％（Ｐ＜０．０１）;主动态ＡⅡ含量升高８０％（Ｐ＜０．０１）。应用ＥＴ抗血清或卡托普利可明显抑制血管损伤诱导的ＶＳＭＣ增殖和内膜增厚。血浆和主动脉ＣＧＲＰ水平在术后３d升高６４％和８９％（Ｐ＜０．０１）, 术后１０d血浆和组织Ａdm分别升高１２９％和１０２％（Ｐ＜０．０１）。在体应用ＣＧＲＰ（２５μg/kg）可显著抑制管损伤诱导的ＶＳＭＣ增殖和内膜增厚（抑制率分别为６６％和７９％,Ｐ＜０．０１）。ＥＴ和ＡⅡ抑制血管ＨＲＧ－１表达,激活丝裂素活化蛋白素酶（ＭＡＰＫ）;ＣＧＲＰ和Ａdm诱导ＨＲＧ－１表达,并抑制ＭＡＰＫ活性。结论 ＥＴ和ＡⅡ可促进损伤血管内增殖,而ＣＧＲＰ和Ａdm具有代偿性抗内膜增殖作用。ＥＴ、ＡⅡ、ＣＧＲＰ和Ａdm等血管活性肽可通过调节ＨＲＧ－１表达和ＭＡＰＫ途径以调控ＶＳＭＣ增殖,影响损伤血管狭窄的形成。     

Adenovirus-mediated gene transfer of TIMP-4 reduces neointimal hyperplasia in balloon-injured rat carotid artery

Objective:To determine the effects of a recombinant replication-deficient adenovirus encoding human tissue inhibitor of metalloproteinase-4(Ad.TIMP-4) on vascular smooth muscle cell(VSMC) function in vitro and neointimal development in the injured rat carotid artery.Methods:Western blotting,gelatin zymography and reverse zymography were used to characterize the expression and functional activity of the TIMP-4 secreted by Ad.TIMP-4-infected VSMCs.The migration and proliferation of VSMCs in vitro were separat...     

适度铜缺乏对大鼠颈动脉内皮剥脱术后MMP-9表达和活性的影响

目的:探讨四硫钼酸盐(TM)引起的适度铜缺乏对大鼠颈动脉球囊损伤后内膜增生和基质金属蛋白酶-9(MMP-9)活性和表达的影响. 方法:SD雄性大鼠随机分为铜缺乏组(TM组)和对照组,TM组术前2 wk及术后给予TM强饲,使血清铜蓝蛋白降至基础值的(20±2)%;对照组给予蒸馏水强饲. 每组分为5个时相点(1,3,7,14 d),建立颈总动脉球囊损伤模型,于术后相应时间点处死动物. 利用含1 g/L明胶的SDS-PAGE 非变性凝胶电泳检测各点损伤的颈总动脉组织MMP-9活性,Western blot法检测MMP-9蛋白表达水平. 结果:TM组血管内膜增生程度较对照组显著降低,管腔无明显狭窄. 术后1～7 d,TM组MMP-9活性显著低于对照组,TM组MMP-9蛋白表达水平也较对照组明显降低(P＜0.01). 结论:TM诱导的适度铜缺乏能够显著抑制MMP-9的表达和活性,这可能是起抑制血管球囊损伤术后再狭窄的机制之一.