Ang-及其受体Tie-在骨肉瘤中的表达

目的 研究Ang-2及其受体Tie-2在骨肉瘤的表达情况.方法 选取唐山市第二医院2009年1月至2011年1月手术切除的69例骨肉瘤标本做为病例组.另取12例正常骨组织标本做对照组.采用RT-PCR法检测Ang-2及其受体Tie-2的表达水平.结果 骨肉瘤组Ang-2表达水平显著高于对照组(P<0.05);骨肉瘤组Ang-2 mRNA表达与Tie-2 mRNA表达正相关(r=0.447,P<0.01).结论 Ang-2及其受体Tie-2参与了骨肉瘤的血管生成及调控,在骨肉瘤的发展中起着重要的作用.     

丁苯酞对缺氧人脐静脉血管内皮细胞Ang-2蛋白表达的影响

目的:探讨药物丁苯酞(NBP)对人脐静脉血管内皮细胞(HUVEC)缺氧损伤的保护作用及其对血管生成素2(Ang-2)表达的影响。方法:体外培养HUVEC,建立稳定的内皮细胞缺氧损伤模型。试验分为正常对照组、缺氧损伤模型组、NBP组,按要求分别给予药物处理后,用CCK-8法检测细胞活力,采用免疫细胞化学方法和图像定量分析技术检测平均吸光度,比较各组Ang-2蛋白表达的变化;Western Blot法检测各组Ang-2蛋白的表达情况。结果:NBP可提高HUVEC的存活率;与正常组比较,缺氧组Ang-2蛋白表达量明显升高(P<0.05);与缺氧组比较,NBP组Ang-2蛋白表达进一步增高(P<0.05)。结论:NBP可以上调Ang-2蛋白的表达,对HUVEC缺氧损伤有一定的保护作用。     

大鼠急性β射线皮肤损伤创面愈合过程中Ang-1及其受体的表达

目的探讨急性β射线皮肤损伤创面难愈合过程中血管生成素1(Ang-1)及其受体Tie-2表达的动态变化。方法雌性大鼠54只分为3组:照射组(n=24),直线加速器产生β射线(45Gy)单次照射大鼠臀部皮肤40mm×40mm,建立急性β射线皮肤损伤模型;烧伤组(n=24),以直径为25mm的恒温电烙铁,温度80℃,时间8s,建立大鼠深Ⅱ度热力烫伤动物模型;对照组(n=6),正常大鼠。取不同时期创面皮肤组织,采用免疫组化SP法及RT-PCR等方法,检测1、2、3、4周不同时相点各组大鼠创面组织中Ang-1蛋白、Tie-2蛋白和Ang-1mRNA、Tie-2mRNA的表达。结果正常大鼠皮肤中Ang-1、Tie-2积分吸光度(A)值低表达;照射组伤后1、2和3周的Ang-1 A值分别为0.130±0.012、0.170±0.013和0.192±0.072,明显低于烧伤组的0.190±0.182、0.332±0.014和0.273±0.014(P<0.05);照射组1、2和3周的Tie-2A值分别为0.112±0.011、0.183±0.012和0.171±0.061,亦明显低于烧伤组的0.170±0.062、0.310±0.013和0.284±0.014(P<0.05);Ang-1mRNA、Tie-2mRNA表达的变化与Ang-1蛋白、Tie-2蛋白相似。结论急性β射线皮肤损伤创面愈合过程中,Ang-1及Tie-2持续低表达可能是急性β射线皮肤损伤创面难愈合的机制之一。     

补阳还五汤对脑出血大鼠脑组织Ang-1和Tie-2表达的影响

目的 探讨补阳还五汤对脑出血大鼠脑组织中促血管生成素1 (Ang-1)和酪氨酸激酶受体2(Tie-2)表达的影响.方法 96只SD大鼠随机分为三组,每组32只.A组和M组注射胶原蛋白酶Ⅶ构建大鼠脑出血模型,S组为假手术组.A组每日采用补阳还五汤2mL灌胃,每天2次,连续治疗14d.A组和M组在脑出血建模后第1、3、7、14天获取大鼠出血部位脑组织,实时荧光定量PCR检测脑组织中Ang-1和Tie-2mRNA表达,分析其相关性.结果 M组Ang-1和Tie-2 mRNA表达水平在第1天低于S组(P＜0.01),但第7、14天高于S组(P＜0.01).第3、7、14天,A组Ang-1和Tie-2mRNA表达水平均高于M组(P＜0.05或P＜0.01).Ang-1与Tie-2mRNA表达水平呈正相关(r=0.89,P＜0.01).结论 脑出血大鼠脑组织中Ang-1和Tie-2mRNA表达水平先下降后升高,补阳还五汤可能通过上调Ang-1和Tie-2mRNA表达发挥治疗脑出血的作用.     

内皮抑素基因治疗裸鼠子宫内膜异位症对Ang-2/Tie-2的影响

目的:探讨内皮抑素对裸鼠子宫内膜异位病灶中血管生成素2(Ang-2)/酪氨酸蛋白激酶受体2(Tie-2)系统表达的影响.方法:采用腹膜种植方法建立子宫内膜异位症(EMs)裸鼠模型共60只.造模1周后,随机分成内皮抑素组、空病毒组和磷酸盐缓冲液(PBS)对照3组,每组各20只,观察各组镜下子宫内膜组织学变化,并采用免疫组化法检测各组异位内膜组织Ang-2及Tie-2的表达情况.结果:成功建立裸鼠EMs模型.空病毒组和PBS组腺体增生明显,间质血管丰富;内皮抑素组腺体萎缩,间质血管减少.Ang-2、Tie-2均在子宫内膜腺上皮细胞、间质细胞中表达,定位于细胞质.Ang-2在内皮抑素组的阳性率(40%)显著低于空病毒组(75%)和PBS组(80%)(均P＜0.05);Tie-2在内皮抑素组的阳性率(45%)显著低于空病毒组(80%)和PBS组(85%)(均P＜0.05).结论:内皮抑素对裸鼠EMs模型异位病灶中Ang-2/Tie-2血管生成途径有抑制作用,为其抗血管生成治疗EMs的临床应用奠定基础.     

Ang-2、Tie-2与ER-α在子宫内膜异位症中的表达及意义

目的:探讨血管生成素2(Ang-2)及其酪氨酸蛋白激酶受体2(Tie-2)和雌激素受体α(ER-α)在子宫内膜异位症(内异症)发病中的表达.方法:选择30例内异症患者的在位内膜作为内异症组,30例卵巢其他良性肿瘤患者的子宫内膜作为对照组,增殖期和分泌期各15例,应用免疫组织化学SP法检测Ang-2、Tie-2和ER-α在其中的表达.结果:Ang-2和Tie-2主要在子宫内膜的腺上皮表达,血管内皮和间质也有少许表达,但较腺上皮表达少,定位于细胞浆.ER-α在子宫内膜腺上皮和间质均有表达,定位于细胞核.内异症组的增殖期和分泌期内膜中Ang-2表达,分泌期时Tie-2的表达,增殖期ER-α的表达均显著高于对照组(P<0.05或P<0.01).2组增殖期时Tie-2的表达,分泌期时ER-α的表达差别无统计学意义(P>0.05).Ang-2及Tie-2在2组中的表达均是分泌期高于增殖期,ER-α则是增殖期高于分泌期(P<0.05).结论:内异症在位内膜分泌期的Ang-2和Tie-2及增殖期ER-α高表达可能与内异症的发病有密切关系.     

脉络宁注射液对人血管内皮细胞缺氧损伤的保护作用

目的:研究脉络宁注射液对人脐静脉血管内皮细胞缺氧损伤的保护作用及其机制。方法:常规进行人血管内皮细胞(HUVECs)培养,将细胞随机分为正常对照组、缺氧组和脉络宁20 mg.L-1组。采用CCK-8法检测细胞存活率;Hochest33258荧光染料检测细胞凋亡率;RT-PCR法检测各组细胞中血管内皮生长因子(VEGF),血管生成素-2(Ang-2)mRNA表达水平。结果:脉络宁注射液可显著提高缺氧损伤细胞的存活率(P<0.05);与正常对照组比较,缺氧组细胞内VEGF和Ang-2 mRNA表达水平明显增高。与缺氧组比较,脉络宁组VEGF和Ang-2的表达进一步增强,各组间比较均有差异(P<0.05)。结论:脉络宁注射液可减轻血管内皮细胞缺氧损伤,上调缺氧血管内皮细胞中VEGF和Ang-2的表达,对血管内皮细胞缺氧损伤有一定的保护作用。     

生化糖浆对药物致不完全流产早孕大鼠子宫内膜血管新生及作用机制研究

目的 研究生化糖浆对药物致不完全流产早孕大鼠子宫内膜血管新生及作用机制.方法 将受孕7 d的早孕大鼠灌胃米非司酮和米索前列醇,复制不完全流产模型,将不完全流产模型大鼠分为模型组、阳性对照组、生化糖浆低剂量组、生化糖浆中剂量组和生化糖浆高剂量组,将正常受孕大鼠作为正常对照组.采用免疫组化法检测大鼠子宫内膜中微血管密度(MVD)和酪氨酸激酶受体(Tie-2),采用酶联吸附法检测血清中促血管生成素-1(Ang-1)和促血管生成素-2(Ang-2).结果 MVD和Tie-2积分吸光度以及血清中的Ang-1和Ang-2水平显著性的低于正常对照组(P<0.05),阳性对照组、生化糖浆中剂量组和生化糖浆高剂量组的MVD和Tie-2积分吸光度以及Ang-1和Ang-2水平显著性的高于模型组(P<0.05).结论 生化糖浆对药物流产大鼠子宫内膜中的血管新生有显著的促进作用,其作用机制可能与高大鼠子宫中的Ang-1和Ang-2以及Tie-2的表达水平有关.     

Ang-2和HIF-1α在膀胱移行细胞癌中的表达及临床意义

目的探讨血管生成素-2和缺氧诱导因子-1α在膀胱移行细胞癌中的表达及其与膀胱移行细胞癌病理分级、临床分期之间的关系,以及两者表达之间的相互关系。方法选取经临床病理诊断的膀胱移行细胞癌标本60例,正常膀胱组织20例。应用免疫组化染色方法检测Ang-2和HIF-1α在膀胱移行细胞癌中的表达情况。结果在正常膀胱组织中Ang-2和HIF-1α均无表达,但均呈过表达在膀胱移行细胞癌标本中。Ang-2和HIF-1α在膀胱移行细胞癌中的阳性表达率分别为47.7%(28/60)、41.7%(25/60)。Ang-2和HIF-1α在膀胱移行细胞癌中阳性表达率随其病理分级和临床分期增加而升高。Ang-2与HIF-1α的等级相关系数rs经统计检验为0.498,差异有统计学意义(P<0.05)。结论膀胱组织在癌变过程中获得了Ang-2、HIF-1α受体且随膀胱移行细胞癌的病理分级、临床分期增加而升高,表明Ang-2、HIF-1α阳性率越高,膀胱移行细胞癌的恶性度越高,浸润越深。膀胱移行细胞癌中Ang-2和HIF-1α的表达具有两两正相关关系;相互作用共同参与膀胱移行细胞癌的发生、发展,影响肿瘤血管形成。     

胃癌患者血清VEGF-C、Ang-2的表达及临床意义

目的 研究胃癌患者血清中血管内皮生长因子-C (VEGF-C)、血管生成素-2(Ang-2)的表达变化及其与胃癌的临床病理特征的关系,探讨VEGF-C与Ang-2在胃癌中的相互关系.方法 收集120例胃癌患者及49例健康者(对照组)血清,采用酶联免疫吸附技术(ELISA)检测血清中VEGF-C、Ang-2水平.结果 胃癌患者血清中VEGF-C、Ang-2含量较对照组均明显升高,差异具有统计学意义(P＜0.05)；VEGF-C表达水平升高与胃癌淋巴结转移(P＜0.01)、浸润深度(P＜0.05)、TNM分期(P＜0.01)相关；Ang-2表达水平升高与胃癌淋巴结转移(P＜0.01)、浸润深度(P＜0.01)、TNM分期(P＜0.01)相关；VEGF-C与Ang-2表达成正相关关系(r=0.478,P＜0.05).结论 血清中VEGF-C、Ang-2可作为胃癌生物学指标,两者联合可能成为判断胃癌淋巴结转移及预后的重要指标.     

Rac对失血性休克大鼠血管反应性的调节作用

目的探讨Rac在失血性休克大鼠血管反应性调节中的作用。方法采用SD大鼠复制休克模型,取离体血管环,观察休克早期和晚期血管反应性的变化以及Rac激动剂和特异性抑制剂对休克早期和晚期血管反应性的影响;通过酶消化法培养原代血管平滑肌细胞（vascular smoot hmuscle cell,VSMC）,采用双室培养方式分别观察VSMC缺氧10min和90min后VSMC对去甲肾上腺素（norepinephrine,NE）的收缩反应性变化,同时观察Rac活性调节剂对缺氧后VSMC收缩反应性的影响。结果在休克早期和短暂缺氧后,离体血管环和VSMC对NE收缩反应性均有所升高,Rac的激动剂血小板衍生生长因子（platelet derived growth factor,PDGF）可部分降低休克早期或短暂缺氧后血管反应性,Rac特异性抑制剂NSC23766可拮抗由PDGF所引起的血管反应性的变化,而在休克晚期或长时间缺氧后,离体血管环和VSMC对NE收缩反应性明显降低,NSC23766对休克晚期或长时间缺氧所致血管反应性降低有升高作用。结论休克后血管反应性呈双相变化,休克早期升高,休克晚期降低,Rac参与了休克血管反应性的调节。     

Targeting the angiopoietin (Ang)/Tie-2 pathway in the crosstalk between acute myeloid leukaemia and endothelial cells: studies of Tie-2 blocking antibodies,exogenous Ang-2 and inhibition of constitutive agonistic Ang-1 release

Background: The Tie-2 receptor can bind its agonistic ligand Angiopoietin-1 (Ang-1) and the potential antagonist Ang-2. Tie-2 can be expressed both by primary human acute myeloid leukaemia (AML) cells and endothelial cells, and Tie-2-blocking antibodies are now being evaluated in clinical trials for cancer treatment. Design and methods: We investigated the effects of Tie-2-blocking antibodies, exogenous Ang-2 and pharmacological agents on AML cell proliferation and the release of angioregulatory mediators. Results: Tie-2-blocking antibodies had a growth inhibitory effect on human AML cells co-cultured with microvascular endothelial cells, but this inhibition was not observed when leukaemic cells were co-cultured with fibroblasts or osteoblasts. AML cell viability in co-cultures was not altered by anti-Tie-2. Furthermore, anti-Tie-2 decreased hepatocyte growth factor (HGF) levels and increased CXCL8 levels in co-cultures, whereas the levels of endocan (a proteoglycan released by endothelial cells) were not altered. The only significant effects of exogenous Ang-2 were decreased levels of HGF and endocan. Constitutive AML cell release of agonistic Ang-1 was decreased by the proteasomal inhibitor bortezomib and the specific IκB-kinase/NFκB inhibitor BMS-345541. Conclusion: We conclude that various strategies for inhibition of Tie-2-mediated signalling should be considered in AML therapy, possibly in combination with other antiangiogenic strategies.     

三羟异黄酮对失血性休克大鼠肠系膜上动脉收缩反应性的影响

目的研究三羟异黄酮(genistein,GST)对失血性休克大鼠肠系膜上动脉收缩反应性的影响及其可能机制。方法建立大鼠失血性休克(3.9kPa,2h)模型。采用离体血管环张力测定实验,观察三羟异黄酮及酪氨酸蛋白磷酸酶抑制剂钒酸钠(sodiumorthovannadate,Na3VO4)对休克大鼠肠系膜上动脉血管收缩反应性的影响;采用细胞贴附式膜片钳记录技术,观察三羟异黄酮及钒酸钠对休克大鼠肠系膜上动脉平滑肌细胞大电导钙激活钾通道(largeconductancecalciumactivatedpotassiumchannel,BKCa)活动的影响。结果失血性休克导致大鼠肠系膜上动脉对去甲肾上腺素(noradrenine,NE)的收缩反应性降低,三羟异黄酮可在一定的剂量范围内明显改善失血性休克引起的血管低反应性;钒酸钠则可引起休克血管收缩反应性的进一步降低,且该作用可被0.1mmol·L-1TEA部分阻断;进一步的研究显示,失血性休克可引起大鼠肠系膜上动脉血管平滑肌细胞BKCa通道活动的增强,三羟异黄酮可抑制休克血管平滑肌细胞BKCa通道活动,且该作用可被钒酸钠逆转。结论三羟异黄酮可通过干预由PTK介导的酪氨酸蛋白磷酸化,防止失血性休克血管平滑肌细胞BKCa通道活动的增强,从而有效恢复失血性休克大鼠肠系膜上动脉对NE的收缩反应性。     

Beneficial effect of arginine vasopressin on hemorrhagic shock through improving the vascular reactivity

The vascular reactivity and calcium sensitivity were decreased following hemorrhagic shock. Arginine vasopressin (AVP) was beneficial to endotoxic, infectious/spetic and hemorrhagic shock. Our previous studies found that Rho kinase played an important role in the occurrence of calcium desensitization following shock. It was reported that AVP was with stimulation effect of Rho kinase. So we hypothesized that AVP might have beneficial effect on shock via activation of Rho kinase to regulate the calcium sensitivity and vascular reactivity. Hemorrhagic shock (40 mmHg for 2 h) Wistar rats in vivo were adopted to observe the effects of small dose of AVP on hemodynamics, 24-h survival rate, the pressor effect of norepinephrine (NE) and the contractility of superior mesenteric artery (SMA). Isolated SMAs from hemorrhagic shock rats were adopted to observe the effects of AVP on vascular reactivity and calcium sensitivity and its relationship to Rho kinase with an isolated organ perfusion system. The results show that AVP at the concentration of 0.1 U/kg and 0.4 U/kg significantly improved the hemodynamic parameters and the 24-h survival rate of hemorrhagic shock rats. Meanwhile, these dosages of AVP significantly increased the pressor effect of NE and the contractile response of SMA to NE. Y-27632 (3 μg/kg), a Rho kinase specific inhibitor, abolished the beneficial effects of AVP. In vitro, the calcium sensitivity and vascular reactivity of SMA to calcium and NE were significantly decreased following hemorrhagic shock. AVP at the concentration of 0.5 nmol/L and 5 nmol/L significantly increased the calcium sensitivity and vascular reactivity. These effects of AVP were abolished by Y-27632 (10 μmol/L). Taken together, the results suggest that AVP at 0.1 U/kg and 0.4 U/kg is beneficial to hemorrhagic shock by improving the vascular reactivity, which involves activation of Rho kinase.     

Effects of MCI-154 on vascular reactivity and its mechanisms after hemorrhagic shock in rats

The objectives of this study were to investigate the effects of 6-[4-(4'-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride trihydrate (MCI-154), a newly developed cardiotonic agent, on vascular reactivity and contractile responses to extracellular Ca2+ ([Ca2+]o) after hemorrhagic shock and primarily explore its mechanism. In vivo, the effects of MCI-154 (0.1, 0.5, 1.0, and 2.0 mg/kg) on the pressor effect of norepinephrine (NE) in rats subjected to hemorrhagic shock (30 mm Hg for 2 h) were observed and in vitro, the effects of MCI-154 (10(-7), 10(-6), 10(-5), 10(-4) mol/L) on vascular reactivity and contractile responses to [Ca2+]o of superior mesenteric artery (SMA) from hemorrhagic shock rats and its relationship to Rho-kinase, protein kinase C (PKC), and protein kinase G (PKG) were observed. The results showed that the NE-induced pressor response after hemorrhagic shock was significantly decreased (P<0.01), and MCI-154 made it decrease further. In vitro, MCI-154 further decreased the contractile responses of SMA to NE and Ca2+ after hemorrhagic shock as compared with untreated hemorrhagic shock group (P<0.01). Angiotensin II (Ang II), with Rho-kinase stimulating action, and PMA, a PKC agonist increased the contractile responses to [Ca2+]o of SMA after hemorrhagic shock. MCI-154 (10(-5) mol/L) partly inhibited Ang II and PMA-induced increase of the contractile responses to [Ca2+]o of SMA (P<0.01). KT-5823, the PKG antagonist, antagonized MCI-154-induced decrease of the contractile responses to [Ca2+]o. Taken together, these results suggested that the vascular reactivity and contractile responses to [Ca2+]o of vascular smooth muscle after hemorrhagic shock were significantly decreased. MCI-154 worsened hemorrhagic shock-induced vascular hyporeactivity and the decrease of contractile responses to [Ca2+]o. These effects were possibly regulated by Rho-kinase, PKC, and PKG, but this needs further confirmation.     

Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats

Aim:

Ryanodine receptor 2 (RyR2) is a critical component of intracellular Ca²⁺ signaling in vascular smooth muscle cells (VSMCs). The aim of this study was to investigate the role of RyR2 in abnormal vascular reactivity after hemorrhagic shock in rats.

Methods:

SD rats were hemorrhaged and maintained mean arterial pressure (MAP) at 40 mmHg for 30 min or 2 h, and then superior mesenteric arteries (SMA) rings were prepared to measure the vascular reactivity. In other experiments, SMA rings of normal rats and rat VSMCs were exposed to a hypoxic medium for 10 min or 3 h. SMA rings of normal rats and VSMCs were transfected with siRNA against RyR2. Intracellular Ca²⁺ release in VSMCs was assessed using Fura-2/AM.

Results:

The vascular reactivity of the SMA rings from hemorrhagic rats was significantly increased in the early stage (30 min), but decreased in the late stage (2 h) of hemorrhagic shock. Similar results were observed in the SMA rings exposed to hypoxia for 10 min or 3 h. The enhanced vascular reactivity of the SMA rings exposed to hypoxia for 10 min was partly attenuated by transfection with RyR2 siRNA, whereas the blunted vascular reactivity of the SMA rings exposed to hypoxia for 3 h was partly restored by transfection with RyR2 siRNA. Treatment with the RyR agonist caffeine (1 mmol/L) significantly increased Ca²⁺ release in VSMCs exposed to hypoxia for 10 min or 3 h, which was partially antagonized by transfection with RyR2 siRNA.

Conclusion:

RyR2-mediated Ca²⁺ release contributes to the development of bi-phasic vascular reactivity induced by hemorrhagic shock or hypoxia.     

Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease

ABSTRACT

Introduction: The Tie-2/Angiopoietin pathway is a therapeutic target for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Activation of Tie-2 receptor via Ang-1 maintains vascular stability to limit exudation. Ang-2, a competitive antagonist to Ang-1, and VE-PTP, an endothelial-specific phosphatase, interfere with the Tie-2-Ang-1 axis, resulting in vascular leakage.

Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study. AKB-9778 monotherapy did not reduce diabetic retinopathy severity score compared to placebo. AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases.

Expert opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities.     

当归补血汤对脑缺血再灌注损伤大鼠血管新生及Ang-1、Ang-2、VEGF和Tie-2的影响

目的 探究当归补血汤对脑缺血再灌注损伤大鼠血管新生及Ang-1、Ang-2、VEGF和Tie-2的影响.方法 采用线栓法复制脑缺血再灌注损伤大鼠模型,模型复制后随机分为假手术组、模型组、当归补血汤低剂量组和当归补血汤高剂量组.连续给药14 d,评价术后第1天和第14天的神经功能,免疫组化检测脑缺血区域及周围的微血管密度和Tie-2表达水平,酶联免疫吸附法检测血清中Ang-1和Ang-2浓度,Weatern Blotting法检测脑组织中VEGF表达水平.结果 连续给药14 d后当归补血汤高剂量组和低剂量组的神经功能评分、MVD、Ang-1和Ang-2浓度、Tie-2和VEGF表达水平均显著高于模型组,且随着当归补血汤剂量的增加,各指标亦显著性增加.结论 当归补血汤促进脑缺血再灌注损伤大鼠的神经功能的恢复,而其作用机制可能为通过促进Ang-1、Ang-2、Tie-2和VEGF的表达而使脑缺血部位的血管新生.     

肌内皮缝隙连接在失血性休克大鼠内皮依赖和非内皮依赖的血管舒/缩功能调节中的作用

目的 研究肌内皮缝隙连接(myo-endothelial gap junction,MEGJ)通道在失血性休克大鼠肠系膜上动脉血管(SMA)的内皮依赖和非内皮依赖的血管收缩/舒张功能调节中的作用.方法 利用在体血管管径测定技术,观察MEGJ的阻断剂18α-甘草次酸(18α-GA)对非内皮依赖的血管收缩剂去甲肾上腺素(N...     

永久性大脑局灶缺血后angiopoietin—2和血管内皮生长因子在小鼠大脑皮层的表达

目的:研究永久性大脑局灶缺血后血管内皮生长因子(VEGF)、angiopoietin-1(Aug-1)、Aug-2、Tie-1和Tie-2在C57BL/6小鼠大脑皮层的表达.方法:采用半定量逆转录聚合酶链反应(RT-PCR)研究VEGF、Aug-1、Aug-2、Tie-1和Tie-2 mRNA表达的变化.采用免疫组织化学法研究VEGF和Aug-2蛋白的表达.结果:在正常小鼠大脑皮层VEGF、Aug-1、Aug-2、Tie-1和Tie-2 mRNA表达水平很低.当大脑中动脉阻断(MCAO)后,在梗塞皮层VEGF、Ang-2和Tie-2 mRNA表达显著增加,并且可维持到第7天.但Ang-1和Tie-1 mRNA表达在梗塞皮层无明显变化.在正常小鼠大脑皮层,几乎观察下到VEGF和Ang-2蛋白的表达.MCAO后8小时Ang-2蛋白发达在皮层梗塞区明显增加,1天后可在梗塞灶周边区看到Ang-2蛋白增加;而VEGF蛋白则在MCAO后2小时在皮层梗塞区即显著升高,1天后在梗塞灶周边区可观察到VEGF蛋白增加.不论在皮层梗塞区还是在梗塞灶周边区,Ang-2和VEGF免疫阳性都限于内皮细胞和胶质样细胞.结论:大脑局灶缺血后Ang-2和VEGF表达增加,可能有利于缺血大脑皮层的血管新生.