转化生长因子-β1在肝细胞性肝癌中表达增强

目的转化生长因子－β１（ＴＧＦβ１）在细胞生长的负性调节上有重要作用,是肝细胞生长和增殖的强抑制物但肝癌（ＨＣＣ）患者肝组织中ＴＧＦβ１ｍＲＮＡ表达高．现检测ＨＣＣ患者外周血中ＴＧＦβ１ｍＲＮＡ表达,血清ＴＧＦβ１水平,以及肝组织中ＴＧＦβⅡ型受体（ＴＧＦβＲⅡ）的表达．方法ＨＣＣ患者外周血分离单个核细胞（ＰＢＭＣ）,提取总ＲＮＡ,用反转录聚合酶链反应（ＲＴＰＣＲ）技术扩增ＴＧＦβ１ｍＲＮＡ．血清ＴＧＦβ１水平测定用Ｐｒｏｍｅｇａ公司产的试剂盒．肝组织ＴＧＦβＲⅡ表达的分析用原位杂交法．结果ＨＣＣ患者２０例ＰＢＭＣＴＧＦβ１ｍＲＮＡ用ＲＴＰＣＲ检测阳性率达７０％,对照组阴性．ＨＣＣ患者４０例血清ＴＧＦβ１水平（２７５８ｍｇ／Ｌ±８１０ｍｇ／Ｌ）明显高于对照组（８２７ｍｇ／Ｌ±３７２ｍｇ／Ｌ）．原位杂交表明,ＴＧＦβＲⅡ在ＨＣＣ细胞的胞质中有弱表达．结论ＨＣＣ患者ＴＧＦβ１基因在转录水平和翻译水平上均显示表达增强．ＰＢＭＣ有可能代替肝组织用以检测ＴＧＦβ１ｍＲＮＡ的表达应用于基础与临床的研究．     

原发性肝细胞癌患者转化生长因子β1的基因表达及临床意义

目的研究转化生长因子β１（ＴＧＦβ１）ｍＲＮＡ在原发性肝细胞癌患者中的表达及其临床意义。方法用ＲＴ－ＰＣＲ加ＤｏｔＢｌｏｔ法检测原发性肝细胞癌患者肝组织和外周血单个核细胞（ＰＢＭＣ）中ＴＧＦ－β１ｍＲＮＡ水平，并以正常肝组织和正常人的ＰＢＭＣ为对照。结果ＴＧＦ－β１ｍＲＮＡ水平在原发性肝细胞癌患者组肝组织（２．２２±０．８４，ｎ＝１６）和ＰＢＭＣ中（１．８３±１．２，ｎ＝２５）比较，差异无显著性（Ｐ＞０．０５），但两者均高于正常肝组织（０．９４±０．７６，ｎ＝５）和正常人的ＰＢＭＣ（０．６２±０．４０，ｎ＝１６）水平。结论ＴＧＦ－β１ｍＲＮＡ水平与原发性肝细胞癌有关，ＰＢＭＣ中ＴＧＦ－β１ｍＲＮＡ检测可望作为一项代替肝组织活检的指标，其表达水平与肝癌有关。     

rIFN－a对胃癌细胞表皮生长因子受体表达的调节

用中性红吸收分析法和放射配体结合法分析基因重组干扰素－α（ｒＩＦＮ－α）对胃癌细胞（ＳＧＣ７９０１、ＫＡＴＯⅢ）增殖及其表皮生长因子受体（ＥＧＦ－Ｒ）表达的影响。结果显示ｒＩＦＮ－α可明显抑制ＳＧＣ７９０１细胞增殖，与作用时间、剂量相关，而对ＫＡＴＯⅢ增殖无明显抑制作用。采用氯胺Ｔ法自行标记表皮生长因子（ＥＧＦ），配体结合实验Ｓｃａｔｃｈａｒｄ分析结果ＳＧＣ７９０１、ＫＡＴＯⅢ均高表达单一亲和性的ＥＧＦ－Ｒ。ｒＩＦＮ－α降低ＳＧＣ７９０１细胞ＥＧＦ－Ｒ数量，与作用时间、剂量相关，ＥＧＦ－Ｒ亲和性无变化，而对ＫＡＴＯⅢ细胞ＥＧＦ－Ｒ的数量及亲和性均无明显影响。结果提示ｒＩＦＮ－α抑制胃癌细胞生长可能和其下调细胞ＥＧＦ－Ｒ相关。     

慢性乙型肝炎肝细胞MHC抗原表达的免疫组化和免疫电镜的研究

应用单克隆抗体和免疫组化技术，对２２例血清ＨＢｅＡｇ阳性的慢性乙型肝炎患者的肝内ＭＨＣ抗原的表达进行了研究。ＭＨＣ－Ⅰ类抗原在２４例ＣＰＨ和１８例ＣＡＨ患者的肝细胞膜上表达。阳性的肝细胞主要分布在碎屑样、桥样和灶性坏死区。ＭＨＣ－Ⅰ类抗原在肝细胞的表达程度和ＣＤ８＋Ｔ淋巴细胞的肝内浸润和肝病变程度有相关关系。免疫电镜显示，表达ＭＨＣ－Ｉ类抗原的肝细胞和穿过血窦的淋巴细胞密切接触。ＭＨＣ－Ⅱ类（ＨＬＡ－ＤＲ）抗原在１１／１８例的ＣＡＨ患者的肝细胞中表达。阳性的肝细胞呈灶性分布，其表达程度低于ＭＨＣ－Ｉ类抗原。上述结果提示，ＭＨＣ抗原在肝细胞的表达可能在乙型肝炎的发病机制中起重要作用。     

肿瘤坏死因子对鼠甲状腺细胞钙离子的作用

目的　观察 Ｔ Ｎ Ｆα对甲状腺细胞肌醇脂质／ 钙离子（ Ｉｎｓ／ Ｃａ２ ＋ ） 系统的作用。方法　利用激光扫描共聚焦显微镜（ Ｌ Ｓ Ｃ Ｍ） 观察 Ｔ Ｎ Ｆα对鼠甲状腺 Ｆ Ｒ Ｔ Ｌ５ 细胞内 Ｃａ２ ＋ 的影响。实验前细胞以不含 Ｔ Ｓ Ｈ 的５ Ｈ（５ 种激素） 培养液培养３ 天，将待测细胞以 Ｆｌｕｏ３ 负载，分别加入不同浓度的 Ｔ Ｎ Ｆα，以 Ｌ Ｓ Ｃ Ｍ 扫描（４８８ｎｍ ） 测定细胞内 Ｃａ２ ＋ ，观察 Ｔ Ｎ Ｆα的作用。结果　１ ． Ｔ Ｎ Ｆα可降低 Ｆ Ｒ Ｔ Ｌ５ 细胞内基础的 Ｃａ２ ＋ 水平，其效应随 Ｔ Ｎ Ｆα浓度的增加而增强。２ ． Ｔ Ｎ Ｆα可抑制 Ｔ Ｓ Ｈ 刺激甲状腺 Ｆ Ｒ Ｔ Ｌ５ 细胞 Ｃａ２ ＋ 升高的效应。结论　 Ｔ Ｎ Ｆα可以通过抑制甲状腺细胞 Ｉｎｓ／ Ｃａ２ ＋ 系统发挥其抑制效应。     

反义核苷酸干预血管成形术后平滑肌细胞生长因子基因表达的研究

为了研究反义核苷酸对平滑肌细胞（ＳＭＣ）及生长因子基因表达的影响。本实验对兔髂动脉粥样硬化模型行血管成形术；应用Ｎｏｒｔｈｅｒｎ印迹杂交和ＲＴ－ＰＣＲ方法观察反义核苷酸对体外兔髂动脉ＳＭＣ增殖及转化生长因子－β１（ＴＧＦ－β１）、表皮生长因子受体（ＥＧＦＲ）、碱性成纤维细胞生长因子（ｂＦＧＦ）基因表达的影响。结果表明：反义核苷酸抑制ＳＭＣ增生，并呈浓度依赖性；反义核苷酸抑制ＴＧＦ－β１和ｂＦＧＦｍＲＮＡ表达；阳离子脂质体能明显增强反义核苷酸的上述作用。在培养的兔髂动脉ＳＭＣ中ＥＧＦＲｍＲＮＡ表达阴性。结论：反义核苷酸抑制兔髂动脉ＳＭＣ增生与抑制ＴＧＦ－β１和ｂＦＧＦｍＲＮＡ表达有密切关系。     

慢性肾功衰竭患者免疫功能紊乱的效应体CD23分子的表达与调控

目的：研究慢性肾功能衰竭（ＣＲＦ）患者免疫功能紊乱的效应体ＣＤ２３分子的表达与调控。方法：利用细胞培养和间接免疫荧光技术，比较了ＣＲＦ患者与正常人外周血Ｂ细胞膜ＣＤ２３的表达，并研究重组人白介素４（ｒｈＩｌ－４）和重组人γ干扰素（ｒＨＩＦＮ－γ）对ＣＤ２３的调控作用。结果：ＣＲＦ患者外周血ＣＤ２３＋Ｂ细胞较正常人显著增高；ＩＬ－４能促进ＣＲＦ患者和正常人Ｂ细胞ＣＤ２３的表达；ＩＦＮ－γ可显著抑制ＩＬ－４诱导的Ｂ细胞ＣＤ２３的表达。结论：ＣＲＦ患者存在Ｂ细胞的激活；ＣＲＦ患者和正常人一样，外周血Ｂ细胞ＣＤ２３表达受ＩＬ－４上调和ＩＦＮ－γ下调影响；ＣＤ２３分子不仅是ＣＲＦ患者免疫功能紊乱的效应体，而且可能参与这些患者免疫紊乱的发病机理。     

TGFβ-Ⅱ受体mRNA在胰腺癌中的翻译水平

近年来分子生物学研究表明,生长因子及其受体对胰腺癌细胞的生长行为有显著影响。生长因子受体（ＴＧＦβＲ）有３种亚型,我们用原位杂交技术分析了ＴＧＦβＲ－Ⅱ在人类胰腺癌中的表达、分布及定位和分子生物学与临床资料的相关性。１材料与方法正常人胰腺组织标本１０...     

慢性血吸虫病患者周围血淋巴细胞亚群测定的临床意义

本文对３０例慢性血吸虫病患者，１４０例正常人和８２例各型病毒性肝炎患者作周围血Ｔ淋巴细胞亚群、细胞膜表面免疫球蛋白（ＳｍＩｇ）和Ｅ玫瑰花结形成细胞（ＥＲＦＣ）等检测。其结果表明：（１）慢性血吸虫病患者周围血Ｔ淋巴细胞的总Ｔ细胞（ＯＫＴ３）和辅助Ｔ细胞（ＯＫＴ４）及ＥＲＦＣ均明显低于正常人，而抑制杀伤Ｔ细胞（ＯＫＴ８）和ＳｍＩｇ却明显高于正常人，这可能与血吸虫发育过程中虫源性因子的释放有关。（２）急性和慢性病毒性肝炎患者与正常人比较，除ＥＲＦＣ明显较低外，其周围血ＯＫＴ３，ＯＫＴ４，ＯＫＴ８和ＳｍＩｇ均明显较高。血吸虫病患者和病毒性肝炎患者之间的ＯＫＴ８和ＳｍＩｇ无显著性差异而ＯＫＴ３和ＯＫＴ４则有不同，可能与其免疫病理有关。     

肾综合征出血热病毒结构蛋白致病作用的研究

为阐明肾综合征出血热（ＨＦＲＳ）发病机制，用免疫组化法检查了３０例患者ＨＦＲＳ病毒的膜蛋白（ＭＰ）、核蛋白（ＮＰ）在外周血单个核细胞（ＰＢＭＣ）中的表达情况，同时用放免等技术检测了血浆内皮素（ＥＴ）、Ｐ物质（ＳＰ）和肾功能相关指标。发现ＨＦＲＳ患者从４～５病日起至１３病日，ＰＢＭＣ中均有ＭＰ和ＮＰ表达，但随着病情的好转，其表达强度逐渐减弱。经染色鉴定ＭＰ与ＮＰ阳性细胞主要是单核细胞。入院时ＰＢＭＣ中ＭＰ和ＮＰ表达强度并不相同，ＭＰ的表达强度与血浆ＥＴ／ＳＰ比值、病情及肾脏损伤轻重呈平行关系。提示ＨＦＲＳ病毒能侵犯ＰＢＭＣ并在其中复制，表达病毒结构蛋白，而ＭＰ与ＨＦＲＳ病毒的致病作用相关；病程中血浆ＥＴ／ＳＰ比值升高是使肾损加重的重要因素。     

Relationship between gallium 67 citrate scanning and transferrin receptor expression in lung diseases.

The uptake of gallium 67 (67Ga) into cells is postulated to be through transferrin receptors (TFR) of 67Ga combined with transferrin. We studied the relationship between gallium 67 citrate scanning (67Ga scan) and immunohistochemical TFR expression in lungs of nine patients with lung cancer and eight patients with diffuse interstitial lung diseases. We found that lung cancer tissues of positive 67Ga scan expressed TFR, but those of a negative scan did not. In all of the five patients with idiopathic pulmonary fibrosis (IPF), TFR were expressed on the membrane of alveolar macrophages that formed clusters. However, TFR were not expressed in lymphocytes, neutrophils, type 2 alveolar epithelial cells, and endothelial cells. In two patients with sarcoidosis and a patient with pneumoconiosis, TFR were expressed positively only on the membrane of foamy alveolar macrophages and epithelioid cells of granuloma. These findings suggest that 67Ga-citrate initially combines with transferrin in the blood and then the complex is incorporated into cells through TFR. Therefore, 67Ga scan could be positive when cells have TFR and one should be able to observe cancer cells, clusters of alveolar macrophages, and epithelioid cells through the imaging of 67Ga scan in lung cancer and diffuse interstitial lung diseases.     

TfR2 expression in human colon carcinomas

Different proteins regulate iron metabolism at the level of various tissues. Among these is a second transferrin receptor (TfR2) that seems to play a key role in the regulation of iron homeostasis. Although TfR2 expression in normal tissues is restricted at the level of the liver, we observed that TfR2 is frequently expressed in cancer cell lines. Taking advantage of this observation we investigated TfR2 expression in primary colon cancers, and showed that this receptor is expressed in about 26% of cases. TfR2 expression in colon cancer is not related to histological grade, but is preferentially associated with mucinous tumors. In colon cancer cell lines, TfR2 is localized in membrane lipid rafts, induces ERK1/ERK2 phosphorylation, when activated by its ligand transferring, and is preferentially expressed during S-M phases of the cell cycle.The presence of TfR2 on the membrane of colon cancer cells may contribute the growth advantage to these cells.     

Successful treatment-free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells

There is currently no biomarker that reliably predicts treatment-free remission (TFR) in chronic myeloid leukaemia (CML). We characterised effector and suppressor immune responses at the time of tyrosine kinase inhibitor (TKI) cessation in patients from the CML8 and CML10 clinical studies. Natural killer (NK) cells with increased expression of activating NK receptors were higher in patients who achieved TFR. There was no difference in the proportion of CD4⁺ or CD8⁺ T cells. Furthermore, we found that FoxP3⁺ regulatory T cells (T reg) and monocytic myeloid-derived suppressor cells (Mo-MDSCs) were concomitantly decreased in TFR patients, suggesting that the effector and suppressor arms of the immune system work in concert to mediate TFR. A discovery cohort (CML10) was used to generate a predictive model, using logistic regression. Patients classified into the high-risk group were more likely to relapse when compared with the low-risk group (HR 7·4, 95% CI 2·9-19·1). The model was successfully validated on the independent CML8 cohort (HR 8·3, 95% CI 2·2–31·3). Effective prediction of TFR success may be obtained with an effector-suppressor score, calculated using absolute NK cell, T reg, and Mo-MDSC counts, at TKI cessation, reflecting the contribution of both immune suppressors and effectors in the immunobiology underlying successful TFR.     

A critical role for murine transferrin receptor 2 in erythropoiesis during iron restriction

Effective erythropoiesis requires an appropriate supply of iron and mechanisms regulating iron homeostasis and erythropoiesis are intrinsically linked. Iron dysregulation, typified by iron‐deficiency anaemia and iron overload, is common in many clinical conditions and impacts the health of up to 30% of the world's population. The proteins transmembrane protease, serine 6 (TMPRSS6; also termed matriptase‐2), HFE and transferrin receptor 2 (TFR2) play important and opposing roles in systemic iron homeostasis, by regulating expression of the iron regulatory hormone hepcidin. We have performed a systematic analysis of mice deficient in these three proteins and show that TMPRSS6 predominates over HFE and TFR2 in hepcidin regulation. The phenotype of mice lacking TMPRSS6 and TFR2 is characterized by severe anaemia and extramedullary haematopoiesis in the spleen. Stress erythropoiesis in these mice results in increased expression of the newly identified erythroid iron regulator erythroferrone, which does not appear to overcome the hepcidin overproduction mediated by loss of TMPRSS6. Extended analysis reveals that TFR2 plays an important role in erythroid cells, where it is involved in terminal erythroblast differentiation and the regulation of erythropoietin. In conclusion, we have identified an essential role for TFR2 in erythropoiesis that may provide new targets for the treatment of anaemia.     

TFR和VEGF基因双顺反子慢病毒感染骨髓内皮祖细胞的研究

目的:研究转铁蛋白受体 (transferrin receptor,TFR)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的双基因共表达慢病毒载体是否能介导目的基因在中华小型猪骨髓内皮祖细胞（endothelial progenitor cells,EPCs）中的有效表达。方法:通过分子克隆技术构建双顺反子慢病毒表达载体pLenti-GFP-TIR;分离培养中华小型猪骨髓EPCs,用流式细胞仪(FCM)检测细胞表面抗原CD31和Flk-1的表达;并利用Lipofectin 2000将含目的基因的转移质粒与pRsv-REV、pMDlg-pRRE及pMD2G共转染293T细胞并进行慢病毒包装。72 h后,收集病毒上清,感染中华小型猪骨髓EPCs,并通过RT-PCR法检测TFR和VEGF基因的表达。结果:①成功地构建了双顺反子慢病毒表达载体pLenti-GFP-TIR;②FCM检测证实,分离的细胞为骨髓EPCs;包装好的慢病毒颗粒可成功地感染中华小型猪骨髓EPCs;③RT-PCR法检测表明,TFR和VEGF呈高水平的表达。结论:TFR和VEGF基因双顺反子慢病毒载体Lenti-GFP-TIR可有效地转移目的基因至中华小型猪骨髓EPCs中,并成功地表达目的基因,为进一步探讨移植细胞分子成像奠定了基础。     

血清可溶性转铁蛋白受体水平与慢性阻塞性肺疾病患者认知障碍程度的相关性研究

背景目前,血清可溶性转铁蛋白受体(sTFR)水平与慢性阻塞性肺疾病(COPD)患者认知障碍的关系尚未完全明确。目的探讨血清sTFR水平与COPD患者认知障碍程度的相关性。方法选取2017年2月-2019年7月在西安交通大学第一附属医院就诊的COPD患者248例作为观察组,另选取同期健康体检者250例作为对照组;另根据贫血程度将COPD患者分为轻度组38例、中度组45例、重度组19例及非贫血组146例。比较对照组、观察组及轻度组、中度组、重度组、非贫血组患者血清sTFR、内皮素1 (ET-1)、铁调节素(hepcidin)、8-羟基脱氧尿苷酸(8-OHdG)、低氧诱导因子1α(HIF-1α)水平及蒙特利尔认知评估量表(MoCA)评分;血清sTFR水平、MoCA评分与COPD患者血清ET-1、hepcidin、8-OHdG、HIF-1α水平间的相关性分析及血清sTFR水平与COPD患者MoCA评分的相关性分析均采用Pearson相关分析。结果 (1)观察组患者血清sTFR、ET-1、hepcidin、8-OHdG、HIF-1α水平高于对照组,MoCA评分低于对照组(P<0.05)。(2)轻度、中度、重度组患者血清sTFR、ET-1、hepcidin、8-OHdG、HIF-1α水平高于非贫血组,MoCA评分低于非贫血组(P<0.05);中度、重度组患者血清sTFR、ET-1、hepcidin、8-OHdG、HIF-1α水平高于轻度组,MoCA评分低于轻度组(P<0.05);重度组患者血清sTFR、ET-1、hepcidin、8-OHdG、HIF-1α水平高于中度组,MoCA评分低于中度组(P<0.05)。(3) Pearson相关分析结果显示,血清sTFR水平与COPD患者血清ET-1 (r=0.482)、hepcidin(r=0.682)、8-OHdG(r=0.513)、HIF-1α(r=0.441)水平均呈正相关(P<0.05),MoCA评分与COPD患者血清ET-1 (r=-0.461)、hepcidin (r=-0.515)、8-OHdG(r=-0.485)、HIF-1α(r=-0.437)水平均呈负相关(P<0.05);血清sTFR水平与COPD患者MoCA评分呈负相关(r=-0.481,P<0.05)。结论随着贫血程度加重,COPD患者血清sTFR水平升高、认知障碍程度加重,且血清sTFR水平与COPD患者认知障碍程度有关。     

Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma)

Background The aim of this study was to survey the effect of deposited iron on the cell kinetics of hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) in Myanmar (Burmese) patients. Methods Formalin-fixed and paraffin-embedded liver tissues from 34 Myanmar patients with HCC were used. To detect iron deposition, Prussian blue staining was performed. Cell proliferation and apoptosis were assessed by Ki-67 staining and by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay, respectively. HCV RNA was detected by in situ hybridization, and HCV protein, Fas and Fas ligand (FasL) were localized by immunohistochemistry. To identify the subtype of lymphocytes, CD8 was used as a surface marker. Results Iron deposition was found in 43% of the HCC cases, and was heavier in moderately differentiated HCC than in well-differentiated HCC. The Ki-67 labeling index (LI) in cancer cells was higher in Prussian blue-positive-HCC than in -negative HCC (3.8 ± 2.2 vs 1.5 ± 1.7, mean ± SD; P = 0.0067), whereas there was no significant difference between these groups in TUNEL LI. HCV protein was localized in cancer cells, and was found in 89% of the patients. In addition, Fas was expressed in HCC cells, and FasL was localized in HCC cells as well as in infiltrating CD8+ T lymphocytes. The frequency of apoptosis of HCC cells was correlated significantly with the population density of infiltrating CD8+ T lymphocytes. Conclusions Our results indicated that, in Myanmar patients with HCC, iron deposition might accelerate hepatocarcinogenesis, by promoting cancer cell proliferation, without affecting the Fas/FasL apoptotic system.     

Troglitazone, a peroxisome proliferator-activated receptor γ ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells

AIM： To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ （PPARγ） ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS： Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-（4-,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase- mediated nick end labeling of DNA fragmentation sites （TUNEL） assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting. RESULTS： Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax. CONCLUSION： PPARγ ligands inhibit growth and induce apoptosis of liver cancer cells, and may have applications for the prevention and treatment of liver cancer.     

Altered expression of iron regulatory proteins with aging is associated with transient hepatic iron accumulation after environmental heat stress

An increasing body of evidence suggests that dysregulation of iron metabolism contributes to age-related pathologies. We have previously observed increased hepatic iron with aging, and that environmental heat stress stimulates a further increase in iron and oxidative liver injury in old rats. The purpose of this study was to determine a mechanism for the increase in hepatic iron in old rats after heat stress. Young (6 mo) and old (24 mo) Fischer 344 rats were exposed to two heating bouts separated by 24 h. Livers were harvested after the second heat stress, and protein levels of the iron import protein, transferrin receptor-1 (TFR1), and the iron export protein, ferroportin (Fpn) were determined by immunoblot. In the nonheated condition, old rats had lower TFR1 expression, and higher Fpn expression. After heat stress, TFR1 declined in the old rats, and iron chelation studies demonstrated that this decline was dependent on a hyperthermia-induced increase in iron. TFR1 did not change in the young rats after heat stress. Since TFR1 is inversely regulated by iron, our results suggest that the increase in intracellular iron with aging and heat stress lower TFR1 expression. Fpn expression increased in both age groups after heat stress, but this response was delayed in old rats. This delay in the induction of an iron exporter suggests a mechanism for the increase in hepatic iron and oxidative injury after heat stress in aged organisms.