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目的观察黄芪百合颗粒对高原低氧环境下小鼠肠黏膜及肠道菌群稳态的保护作用。方法使用高压氧舱建立高原低氧模型小鼠。60只昆明小鼠随机分为空白组、模型组及黄芪百合颗粒制剂低、中、高剂量[1.75、3.5、7g/（kg·d）]组。常规饲养3d后灌胃给药,空白组、模型组给予等量双蒸水,1次/d,连续17d。除空白组外,第15天起各组小鼠每日灌胃30min后于低压氧舱中模拟高海拔环境进行低氧暴露,连续3d。第18天出舱后取小鼠新鲜粪便抹片观察菌群的变化,HE染色观察肠组织的病理形态学改变,免疫组化法检测肠组织中缺氧诱导因子1α（HIF-1α）蛋白的表达变化。结果模型组小鼠肠道球菌及革兰阴性菌百分比（分别为65.2%±2.4%、56.7%±3.3%）明显高于空白组（分别为24.7%±1.2%、23.2%±1.5%,P〈0.05）,小肠和结肠肠黏膜坏死水肿病理评分（分别为3.10±0.99、3.30±0.67）及炎性细胞计数（分别为15.93±3.30、16.40±3.97/HP）明显高于空白组（分别为0.70±0.67、0.80±0.78、4.07±2.12、4.28±2.16/HP,P〈0.05）,肠组织HIF-1α表达水平明显高于空白组（P〈0.05）。与模型组相比,黄芪百合颗粒中、高剂量组肠道球菌百分比（分别为46.7%±2.0%、32.0%±2.6%）及革兰阴性菌百分比（分别为34.2%±1.6%、28.0%±2.8%）明显下降（P〈0.05）,小肠和结肠肠黏膜坏死水肿病理评分（小肠分别为2.30±1.33、2.10±0.94,结肠分别为2.50±1.08、1.90±0.99）明显降低（P〈0.05）,炎性细胞计数（小肠分别为13.26±2.34、10.93±3.67/HP,结肠分别为14.40±2.02、11.33±2.96/HP）明显降低（P〈0.05）,肠组织HIF-1α的表达水平明显增高（P〈0.01）。结论黄芪百合颗粒制剂对高原低氧环境下小鼠肠道微生态及肠黏膜屏障具有一定保护作用。

Tumor-induced osteomalacia （TIO） is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 （FGF23） by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-la （HIF-la） in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-la mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-la and FGF23 were co-localized in spindle- shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-la protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-la expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor

目的探讨缺氧诱导因子-1α（HIF-1α）和促红素（EPO）在糖尿病大鼠肾组织中的表达及其与糖尿病肾病的关系。方法用链脲佐菌素（STZ）制造糖尿病大鼠模型并在制模成功后4周和8周取肾组织，采用免疫组化方法及全自动图像分析系统检测糖尿病大鼠。肾组织中HIF-1α及EPO的表达。结果糖尿病大鼠肾小球及肾小管均有HIF-1α及EPO的表达，且随着造模时间的延长HIF-1α及EPO的表达逐渐增加。结论糖尿病肾病由于微循环障碍导致组织缺氧，从而使HIF-1α及EPO的表达上调。这也是糖尿病肾病出现微血管结构异常及新生血管形成从而导致糖尿病肾病发生、发展的可能原因。

目的探讨二氯乙酸（DCA）增强替莫唑胺（TMZ）对人脑胶质瘤细胞的抑制作用及机制。方法通过体外实验，观察DCA单药、TMZ单药以及DCA／TMZ联合对人脑胶质瘤细胞的抑制作用；MTT比色法检测细胞增殖；流式细胞技术检测细胞凋亡及细胞内活性氧（ROS）的变化；激光共聚焦显微镜检测细胞线粒体膜电位（MMP）；蛋白质印迹法检测细胞低氧诱导因子（HIF-1α和p53凋亡通路相关蛋白的表达。结果DCA／TMZ联合更有效抑制胶质瘤细胞增殖、使MMP降低、细胞内ROS增加、细胞凋亡增加；HIF-1α表达下降、p53表达升高。结论DCA能增强TMZ对人脑胶质瘤细胞的抑制作用，其机制与抑制HIF-1α、激活p53凋亡信号通路有关。

目的研究模拟失重环境下大鼠卵巢组织中缺氧诱导因子-1α（HIF-1α）的表达变化。方法取性成熟期健康雌性Wistar大鼠60只作为研究对象,体重200±20g,随机分为10组（n=6）,按模拟失重时相分为悬吊0.25、0.5、1、2、3、5、7、14、21d组和0d组（对照组）。采用尾悬吊法建立模拟失重动物模型。各组大鼠卵巢组织中HIF-1α的表达分别应用免疫组织化学和RT-PCR方法进行检测。结果各实验组及对照组大鼠卵巢卵泡卵母细胞、颗粒细胞和膜细胞中均可见HIF-1α阳性染色细胞。对照组大鼠卵巢HIF-1α染色阳性颗粒主要位于细胞质中,悬吊0.25d和0.5d组大鼠卵巢卵母细胞、颗粒细胞和膜细胞的HIF-1α颗粒由细胞质向细胞核转移;尾悬吊1d组HIF-1α表达情况与对照组接近,HIF-1α核染色消失。尾悬吊0.25d、0.5d大鼠卵巢HIF-1αmRNA表达水平显著高于对照组（P〈0.05）,持续尾悬吊1d以后各组卵巢HIF-1α的蛋白和mRNA水平逐渐恢复至对照组水平。结论尾悬吊模拟失重使大鼠卵巢组织中HIF-1α蛋白及mRNA表达发生明显变化,早期同步过表达,提示卵巢HIF-1α表达变化与失重应激反应和失重耐受有密切关系。

目的观察HIF-1α与NF-κB通路在胰腺癌缺氧调节中的作用,及对下游增殖、侵袭、转移相关因子的影响。方法体外缺氧培养胰腺癌细胞株Mia-PaCa2;分别在0、4、6、8 h时间点用Realti me-PCR和Western blot测定HIF-1α及下游相关因子VEGF、CXCR4、5-LOX和COX-2的表达变化;用RNAi技术干扰HIF-1α,及用PDTC封闭NF-κB的表达,观察它们对胰腺癌细胞缺氧调节及肿瘤进展的作用。结果随缺氧时间推移,HIF-1α及下游相关因子相应上调,其中HIF-1α在mRNA水平的变化无统计学差异,仅在蛋白水平显著上调;当HIF-1α表达被干扰后,其下游相关因子也相应下调,显示了对HIF-1α的依从性;当NF-κB表达被PDTC封闭后,HIF-1α及其下游相关因子呈下调趋势。结论缺氧状态下,胰腺癌细胞通过NF-κB及HIF-1α途径进行自我调节,上调下游相关因子的表达,导致增殖、侵袭、转移力增强。并且NF-κB有可能是HIF-1α的上游调控因素。

目的探讨缺氧诱导因子1α（HIF-1α）在盐酸异丙肾上腺素（ISO）诱导的大鼠心房纤维化中的表达及其可能机制。方法健康雄性Wistar大鼠30只,随机均分为空白对照组、ISO组、ISO＋西罗莫司（Rapa）干预组（Rapa组）。于实验15d时处死大鼠取心肌组织,放射免疫法检测血管紧张素Ⅱ（AngⅡ）的含量,HE和Masson染色法观察纤维化程度即胶原容积分数（CVF）,免疫组织化学法、Western blotting检测HIF-1α、转化生长因子β1（TGF-β1）和基质金属蛋白酶9（MMP-9）在大鼠心房纤维化组织中的表达,并分析HIF-1α、TGF-β1、MMP-9蛋白表达量与心房纤维化指标CVF的相关性,以及HIF-1α、TGF-β1、MMP-9蛋白表达量之间的相关性。结果 ISO组、Rapa组AngⅡ含量较空白对照组明显升高（P〈0.01）。空白对照组CVF为15.482%±0.837%,无心房纤维化,而Rapa组、ISO组CVF分别为16.730%±1.052%、86.704%±1.928%,Rapa组较ISO组的心房纤维化程度明显减弱（P〈0.01）。免疫组化及Western blotting检测显示,与空白对照组相比,ISO组HIF-1α、TGF-β1和MMP-9蛋白表达量均明显增加（P〈0.01）,与ISO组比较,Rapa组中HIF-1α、TGF-β1和MMP-9蛋白表达量明显降低（P〈0.01）。HIF-1α、TGF-β1和MMP-9蛋白表达量均与心房纤维化程度（以CVF为评价指标）呈正相关（r=0.987,r=0.988,r=0.917,P〈0.01）;HIF-1α与TGF-β1、MMP-9蛋白表达量呈正相关（r=0.976,r=0.901,P〈0.01）,MMP-9与TGF-β1蛋白表达量亦呈正相关（r=0.912,P〈0.01）。结论在异丙肾上腺素诱导的大鼠心房纤维化过程中,AngⅡ、HIF-1α、TGF-β1、MMP-9发挥着重要作用。

背景与目的业已发现缺氧与肿瘤发生、发展关系密切。本研究的目的是观察地塞米松对低氧小鼠肺组织中缺氧诱导因子-1α（hypoxia inducible factor 1α，HIF-1α）及血管内皮生长因子（vascular endothelial growth factor，VEGF）表达的影响，探讨缺氧与血管新生的关系及地塞米松的作用机制。方法实验用雄性昆明小鼠，随机分为对照组和三个实验组（缺氧3天组、缺氧6天组、缺氧＋激素组）。用免疫组织化学技术检测小鼠肺组织中HIF-1α和VEGF蛋白的表达。结果缺氧组小鼠HIF-1α和VEGF蛋白表达均较对照组显著增加（P〈0．05）；缺氧＋激素组与缺氧组比较，HIF-1α和VEGF蛋白表达显著下降（P〈0．05）。HIF-1α与VEGF表达呈正相关（r=0．730，P=0．007）。结论缺氧可以上调小鼠肺组织中VEGF和HIF-1α的表达，而地塞米松可抑制低氧小鼠VEGF和HIF-1α的表达，具有抗血管生成的作用。

Glyceraldehyde-3-phosphate dehydrogenase （GAPDH）, initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and pnsttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 （HIF-1）, p53, nitric oxide （NO）, and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications （PTMs） occurring in GAPDH in cancer cells result in new activities unrelated to the original glycnlytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described.

Photodynamic therapy （PDT） is a tumor treatment modality in which a tumor- localized photosensitizer is excited with light, which results in local production of reactive oxygen species, destruction of tumor vasculature, tumor hypoxia, tumor cell death, and induction of an anti-tumor immune response. However, pre-existing tumor hypoxia may desensitize tumors to PDT by activating the hypoxia-inducible factor 1 （HIF-1） survival pathway. Therefore, we hypothesized that inhibition of HIF-1 with acriflavine （ACF） would exacerbate cell death in human epidermoid carcinoma （A431） cells. PDT of A431 tumor cells was per- formed using newly developed and optimized PEGylated cationic liposomes containing the photosensitizer zinc phthalocyanine （ZnPC）. Molecular docking revealed that ACF binds to the dimerization domain of HIF-la, and confocal microscopy confirmed translocation of ACF from the cytosol to the nucleus under hypoxia. HIF-1 was stabilized in hypoxic, but not normoxic, A431 cells following PDT. Inhibition of HIF-1 with ACF increased the extent of PDT-induced cell death under hypoxic conditions and reduced the expression of the HIF-1 target genes VEGF, PTGS2, and EDN1. Moreover, co-encapsulation of ACF in the aqueous core of ZnPC-containing liposomes yielded an adjuvant effect on PDT efficacy that was comparable to non-encapsulated ACF. In conclusion, HIF-1 contributes to A431 tumor cell survival following PDT with liposomal ZnPC. Inhibition of HIF-1 with free or liposomal ACF improves PDT efficacy.