首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到19条相似文献,搜索用时 140 毫秒
1.
2.
Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. Results mPAP values were significantly higher than the control values after 7days of hypoxia [(18.4±0.4) mmHg, P<0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0.20±0.02, P<0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia (0.20±0.02, P<0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15±0.02, P<0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P<0.01). Conclusion HIF-1α and VEGF are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.  相似文献   

3.
4.
5.
The hypoxic model to simulate hypoxic microenvironment in solid tumors was established and the effect of hydrocamptothecin (HCPT) on the hypoxia-induced over-expression of HIF-1α and VEGF genes was explored. Human cervical cancer SiHa cells were cultured in vitro under hypoxic conditions (37℃, 5% CO2, 1%O2) and treated with different concentrations of HCPT for 24 h. The mRNA and protein expression levels of HIF-1α, VEGF and Glutl in SiHa cells were detected by semi-quantitative RT-PCR and Western blot respectively. Normoxic control groups were exposed to normoxic conditions for 24 h. Under normoxic conditions, HCPT had no obvious effects on the HIF-1α and VEGF gene expression. Hypoxia induced the up-regulation of HIF-1α protein and downstream VEGF gene, and HCPT showed a dose-dependently inhibitory effect on the hypoxia-induced over-expression of HIF-1α protein and VEGF gene expression in SiHa cells, whereas HCPT had no significant effect on the HIF-1α mRNA expression. No difference in HCPT cytotoxic- ity was observed between hypoxic groups and normoxic control groups. It was suggested that HCPT could inhibite the expression of HIF-1α protein and downstream VEGF gene in hypoxic SiHa cells in a dose-dependent manner, and the inhibitory effect was not related with HCPT cytotoxicity.  相似文献   

6.
Summary: In order to explore the effect of high glucose concentration and high glucose concentration with hypoxia on the production of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), human RPE cells were cultured in 5,56 mmol/L glucose (control group), 5.56 mmol/L glucose with 150 !a mol/L COCl2 (hypoxic group), 25 mmol/L glucose (high glucose group) and 25 mmol/L glucose with 150 μmol/L COCl2 (combination group). RT-PCR was used to detect the expression of HIF-1α and VEGF mRNAs. Western blot analysis was used to measure the levels of HIF-1α and VEGF proteins. Although the small amount of HIF-1α protein was able to be detected in high glucose group but not in control group, there was no significant difference between the expression of HIF-1α mRNA of RPE cells in high glucose group and that of RPE cells in control group. As compared with RPE cells in control group, the mRNA expression and the protein synthesis of VEGF in high glucose group were up-regulated. As compared with RPE cells in hypoxic group, the expression of HIF-1α mRNA of RPE cells in combination group was not different, but the protein synthesis of HIF-1α, the mRNA expression and the protein synthesis of VEGF were more obviously up-regulated. In conclusion, high concentration glucose mainly influence the protein synthesis of HIF-1α of RPE cell, and HIF-1α protein is able to be accumulated in high concentration glucose. Under hypoxia, the HIF-1α protein induced by high concentration glucose is more stable, and the expression of VEGF is obviously increased. It is suggested that high concentration glucose may play a role in retinal neovascularization, especially at ischemia stage of diabetic retinopathy.  相似文献   

7.
Local tissue hypoxia and formation of nasal polyps   总被引:1,自引:0,他引:1  
Objective To explore the response of nasal mucosa epithelial cells to hypoxia in terms of formation of nasal polyps (NP). Methods Epithelial cells of NP and inferior turbinate (IT) were cultured serum-free under normal oxygen and hypoxic circumstances with stimulation of IL-1β and TNFα. The vascular endothelial growth factor (VEGF)mRNA and VEGF protein levels of the cultured cells were detected using in situ hybridization and ELISA, respectively. Results The expression of VEGF mRNA was significantly higher in epithelial cells of NP than in IT exposed to pro-inflammatory cytokines or hypoxia ( P <0.01). VEGF levels were higher in NP epithelial cells than those of IT ( P <0.01) under hypoxia. Conclusion VEGF-induced by hypoxia is very important for the early stages of forming polyps.  相似文献   

8.
9.
Background Ageing is associated with increased incidence of dyslipidemia. To investigate potential molecular mechanisms, the effects of age and fibrate administration on peroxisome proliferator-activated receptor α(PPARα) expression in livers of young and old rats were studied.Methods A total of 16 young (2-month-old) and 16 old rats (24-month-old) were randomly assigned to a control group and fenofibrate group (fenofibrate in a total therapeutic dosage of 0.5% in ratio to each treated rat weight in 14 days). RT-PCR was applied to evaluate hepatic mRNA expression of PPARα and its target genes. Western blotting was used to determine PPARα protein level in liver tissue. Results When compared with 2-month-old rats, the liver tissue from 24-month-old rats showed reduced expression of PPARα mRNA (52%, P<0.05) and protein (109%, P<0.01). Consequently, the mRNA levels of PPAR target genes, LPL, ACO, ACS and CPT-1 were markedly lowered by 19%, 8%, 13% and 9% respectively, and apoCIII increased by 24% in livers from 24-month-old rats, compared with values obtained from 2-month-old rats (P<0.05). Fenofibrate therapy significantly lowered plasma triglyceride and total cholesterol levels in old rats, accompanied with improvement in hepatic expression of genes, including LPL, ACO, ACS, CPT-1 and apoCIII, but no change was found in PPARα expression in livers from either 24-month or 2-month-old rats. Conclusions The decrease in the hepatic PPARα expression is probably directly related to the lipid metabolic disturbances observed in old animals. The beneficial effects of fenofibrate administration in old rats suggests that fibrates may be useful for treating lipid disturbances in old people.  相似文献   

10.
11.
目的探讨缺氧诱导因子-1α(HIF-1α)和血管内皮细胞生长因子(VEGF)在结肠癌组织中的表达与肿瘤组织学分级关系,以及HIF-1α和VEGF之间的相关性;缺养环境对人结肠癌SW480细胞中HIF-1α和VEGF表达的影响。方法用免疫组织化学方法染色显示结肠癌组织中HIF-1α和VEGF的表达,分析HIF-1α、VEGF表达随结肠癌组织学分级的变化及二者之间的关系;RT-PCR研究SW480细胞HIF-1α和VEGF表达在常氧与缺氧时的差异。结果HIF-1α和VEGF蛋白均在结肠癌组织中表达,且表达水平随结肠癌组织学分级提高而上升;各级结肠癌组织中HIF-1α和VEGF的表达呈正相关性;缺氧诱导SW480细胞的VEGF mRNA表达上升。结论HIF-1α和VEGF的表达随结肠癌恶性程度的增高而增强。  相似文献   

12.
P53及缺氧诱导因子-1α表达与结直肠癌血管生成的关系   总被引:5,自引:0,他引:5  
目的探讨抑癌基因p53及缺氧诱导因子-1α(HIF-1α)的表达与结直肠癌血管生成及生物学行为的关系.方法采用免疫组织化学方法检测61例结直肠癌组织中p53、HIF-1α和血管内皮生长因子(VEGF)表达及微血管密度(MVD).结果结直肠癌组织中,HIF-1α阳性表达率为65.6%,其中弱、中、强阳性表达率分别为27.9%、19.7%、18.0%,p53和VEGF阳性表达率分别为42.6%和49.2%,MVD平均为28.7±12.9.HIF-1α、VEGF表达及MVD与肿瘤浸润深度、淋巴结转移、肝转移和Dukes分期密切相关.p53表达与淋巴结转移和肝转移密切相关.p53、VEGF阳性表达率及MVD均与HIF-1α阳性表达程度成正相关(相关系数分别为0.261,P<0.05;0.591,P<0.01;0.795,P< 0.01).结论HIF-1α/VEGF通路在结直肠癌组织血管 生成过程中起重要作用,p53基因失活可能经HIF-1α/VEGF通路促进肿瘤血管生成.p53基因失活、HIF-1 α、VEGF过表达及高MVD与结直肠癌的不良生物学行为有关.  相似文献   

13.
目的研究靶向针对缺氧诱导因子-1α(HIF-1α)的短发夹RNA(shRNA)对人乳腺癌细胞系MCF-7细胞功能的影响。方法氯化钴模拟低氧环境。采用RNA干扰技术,构建针对HIF-1α的shRNA真核表达载体,转染MCF-7细胞。RT-PCR检测RNA干扰后MCF-7中血管内皮生长因子(VEGF)表达的变化。实时定量PCR和Westernblot技术分别检测HIF-1αmRNA和蛋白质水平。Sub-G1测定、AnnexinⅤ荧光标记和DNAladder检测细胞凋亡。流式细胞仪检测细胞周期的变化。结果缺氧后,MCF-7中的HIF-1α表达增加(P<0.01),而凋亡率较常氧降低(P<0.05)。shRNA转染MCF-7后,HIF-1α的表达下调91.63%(P<0.01)。阿糖胞苷诱导或无凋亡诱导剂时,干扰组凋亡率比未转染组分别增高1.75倍(P<0.01)和61.31倍(P<0.01)。与未转染组相比,干扰组中的VEGF下调66.8%(P<0.05)。干扰组细胞周期进程也较未转染组减缓。结论HIF-1α在MCF-7中发挥抗细胞凋亡的作用。本室构建的针对HIF-1α的shRNA能够促进MCF-7凋亡,下调VEGF表达,推迟细胞周期。  相似文献   

14.
~~基质金属蛋白酶及其抑制剂在结-直肠肿瘤中的表达(英文)@陈晶$哈尔滨医科大学附属第二临床医学院!黑龙江哈尔滨150086 @关景明$哈尔滨医科大学附属第二临床医学院!黑龙江哈尔滨150086 @李宝杰$哈尔滨医科大学附属第二临床医学院!黑龙江哈尔滨150086~~~~~~ (上接第14页)relationship to the tissue inhibitors of metalloproteinases and membrane type-1-matrix metalloproteinase[J].BrJ Cancer,2001,84:1664-1670. [14]ReidHM,McElligottAM,McGlyrmH.Phertotypic alterations inCaki-1Cells as a consequence ofTIM…  相似文献   

15.
Yang Y  Duan ZQ  Zhang Q  Shi D  Luo KY  Liu FS 《中华医学杂志》2003,83(8):628-631
目的 探讨缺氧诱导因子 1α(HIF 1α)表达水平与移植静脉再内皮化的关系。方法 将6 0只Wistar大鼠随机分为实验组与对照组 ,前者行颈内静脉 颈总动脉移植术。于术后 7d与 14d切取移植静脉。分别采用反转录多聚酶链反应 (RT PCR)、Western印迹法、免疫组织化学及电镜等检测 ,观察HIF 1α和血管内皮生长因子 (VEGF)表达水平及再内皮化过程。结果 术后 7d与 14d相比较 ,移植静脉再内皮化显著 ;HIF 1αmRNA及其蛋白和VEGF蛋白表达增强 (P均 <0 0 1) ;增生内膜中HIF 1α阳性表达细胞增多。HIF 1α与VEGF表达呈正相关 (r=0 90 2 6 ,P <0 0 1)。结论HIF 1α与移植静脉内皮细胞增殖密切相关 ,其早期表达不足是引起内膜过度增生 (IH)的重要基因之一。  相似文献   

16.
HIF-1α和VEGF在大肠癌组织中的表达及意义   总被引:1,自引:0,他引:1  
目的:探讨缺氧诱导因子-1α(H IF-1α)和血管内皮生长因子(VEGF)在大肠癌组织中的表达及其与大肠癌临床病理特征的关系。方法:免疫组化法检测61例大肠癌组织中H IF-1α及VEGF蛋白表达,并与15例正常大肠组织比较。结果:大肠癌组织中H IF-1α和VEGF的阳性表达率分别为54.10%(33/61)和62.30%(38/61),均明显高于正常对照组(P<0.05);两者呈正相关(r=0.505,P<0.05);Dukes分期中的表达存在显著差异(P<0.05);组织学分级中的表达则无差异性(P>0.05)。结论:H IF-1α及VEGF在肿瘤血管生成和转移中起重要作用,联合检测H IF-1α和VEGF可作为判断大肠癌转移潜能和预后的重要指标。  相似文献   

17.
CoCl2缺氧诱导SW480细胞化疗耐药及其机制   总被引:3,自引:0,他引:3  
目的:研究不同程度的CoCl2化学缺氧条件下SW480细胞的生长情况及对氟尿嘧啶(fluorouracil,FU)的敏感性,以及缺氧诱导因子-1α(hypoxia inducible factor 1 alpha,HIF-1α)和诱导型血红素氧化酶(heme oxygenase-1,HO-1)基因在缺氧条件下的表达,以探讨缺氧条件下导致肿瘤细胞耐药的机制。方法:采用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法测定不同CoCl2浓度下SW480细胞的生长情况及化疗药物FU对SW480细胞的生长抑制作用;采用逆转录聚合酶链反应检测HIF-1α和HO-1 mRNA在缺氧条件下的表达。结果:MTT结果显示,随着CoCl2浓度增加,SW480细胞的增殖速度减慢。FU对SW480的杀伤作用降低。RT-PCR结果显示,CoCl2化学缺氧处理使HIF-1α和HO-1 mRNA表达上调,并呈较好的剂量和时间依赖性关系。结论:CoCl2诱导的体外缺氧可以减缓SW480细胞的生长速度,并降低SW480细胞对FU的敏感性,其机制可能与HIF-1α及HO-1的表达上调有关。  相似文献   

18.
目的探讨外源性人低氧诱导因子-1α(HIF-1α)在成纤维细胞中表达的可行性及其对毛囊周围细胞活性的影响。方法通过脂质体将含有HIF-1αcDNA的真核表达载体pcDNA3.0稳定转染成纤维细胞,应用RT-PCR及Westernblot方法检测HIF-1α在成纤维细胞中的表达,ELISA法检测转染细胞上清液中血管内皮细胞生长因子(VEGF)的表达,RT-PCR方法检测转染后细胞中成纤维细胞生长因子(bFGF)的表达。将该上清加入成纤维细胞及真皮鞘细胞中,MTT法检测加入上清后成纤维细胞及真皮鞘细胞活性。结果RT-PCR及Westernblot可检测出转染后细胞中HIF-1α的表达,MTT检测加入转染上清后成纤维细胞及真皮鞘细胞活性增强(P〈0.05),并且该上清液VEGF的表达显著高于未转染组(P〈0.01)。转染后成纤维细胞的bFGF的mRNA表达显著高于未转染组(P〈0.01)。结论应用脂质体能够成功地将外源性人HIF-1α基因转染成纤维细胞,并进行有效表达,其表达的HIF-1α可增强细胞活性且可诱导转染细胞上清液中VEGF的表达,并增加bFGF的mRNA表达,且转染细胞上清可增强成纤维细胞及真皮鞘细胞活性。推测HIF-1α通过其下游因子VEGF及bFGF促进毛囊相关细胞的活性,为HIF-1α对毛囊作用的进一步研究打下了基础。  相似文献   

19.
[摘要] 目的 检测滑膜HIF-1α、VEGF、CD34表达水平,观察慢性滑膜炎滑膜组织的组织病理学形态改变,了解HIF-1a、VEGF与毛细血管密度(MVD)及组织学分级之间的关系。方法 应用免疫组织化学技术对获得的45例滑膜组织进行HIF-1α、VEGF、CD34染色,HE染色观察慢性滑膜炎滑膜组织病理学形态并进行病理评分及分级,分析相关关系。结果 HIF-1α、VEGF在慢性滑膜炎患者滑膜组织中高表达,表达率分别为68.9%、80%,明显高于正常对照组10%、20%(P<0.05),MVD在慢性滑膜炎组织中较正常对照组明显增高, HIF-1α与VEGF相关(r=0.525,P<0.01),HIF-1α与MVD相关(r=0.867 p<0.01);光镜下可见病变滑膜细胞明显增殖,并伴有大量增生血管,血管周围可见多量淋巴细胞、浆细胞浸润, HIF-1α与滑膜炎的病理学分级正相关(r=0.526,p<0.01)。结论 慢性滑膜炎滑膜中HIF-1α、VEGF与MVD具有相关性,滑膜的增生及滑膜炎的持续可能与HIF-1α引起的血管增生有关,滑膜形态学观察有助于滑膜炎的分级及监测。  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号