转铁蛋白受体-2 mRNA在慢性病贫血大鼠肝脏中的表达

 目的　在建立慢性病贫血（ACD）大鼠动物模型的基础上，通过检测大鼠肝脏转铁蛋白受体-2（TfR2）在促红细胞生成素（EPO）干预前后的表达情况，探讨其在ACD中的作用。方法　在传统佐剂性关节炎大鼠模型基础上，通过追加注射弗氏完全佐剂三次，增强其免疫反应，从而诱发建立贫血模型。对不同处理组大鼠肝脏TfR2 mRNA表达水平进行检测。结果　ACD模型组大鼠肝脏TfR2 mRNA表达比正常对照组升高（P＝0.001），贫血明显；EPO治疗组肝脏TfR2 mRNA表达比ACD模型组大鼠降低（P＝0.001），贫血改善。结论　TfR2可能与ACD有关。     

促红细胞生成素及其受体在卵巢癌细胞的表达及相关作用的实验研究

 目的　检测卵巢癌细胞中的促红细胞生成素（EPO）及其受体（EPOR）表达，以及重组人EPO（rhEPO）对卵巢癌细胞增生的影响，探讨rhEPO在癌性贫血治疗中的意义。方法　RT-PCR方法检测人类卵巢癌细胞株 HO-8910 EPOR mRNA的表达。用流式细胞仪检测rhEPO对卵巢癌细胞凋亡及增生影响。结果　卵巢癌细胞表面有EPOR的表达，rhEPO干预后卵巢癌细胞增生受到抑制（P＜0.01）。结论　EPOR在卵巢癌细胞株HO-8910有表达，rhEPO可抑制卵巢癌细胞的增生。rhEPO可用于卵巢癌伴发的贫血的治疗。     

铁调素在多发性骨髓瘤相关性贫血中的作用机制

贫血是多发性骨髓瘤（multiple myeloma,MM）的常见症状,与预后不良相关。目前认为,MM相关性贫血是一种慢性病性贫血（anemia of chronic disease,ACD）,由慢性炎症刺激所导致。铁调素（hepcidin）是一种机体铁代谢调节激素,它在炎症刺激下表达上调,使铁无法从细胞释放至血浆,造成血清铁降低,进而导致贫血发生。铁调素相关通路是MM相关性贫血发病机制中的中心环节,成为MM相关性贫血治疗的新靶点。促红细胞生成素类制剂（erythropoiesis-stimulating agent,ESA）能有效提高血红蛋白水平,是既往治疗MM相关性贫血的主要方法之一。近年ESA对肿瘤相关性贫血的治疗效果受到质疑,认为ESA可能促进肿瘤进展,并不能改善患者的总体预后。本文主要对MM相关性贫血的发病机制及治疗进行综述,着重阐述铁调素的作用机制,总结ESA的治疗效果,探讨铁调素通路的靶向治疗作用。     

Neuropilin1单克隆抗体对胶质瘤大鼠Bcl-2/Bax表达的影响

目的:研究Neuropilin1单克隆抗体对胶质瘤大鼠Bcl-2/Bax表达的影响。方法:将36只SD大鼠随机分为假手术组、模型组和治疗组,每组12只;假手术组只行颅骨开窗手术,其余各组均建立胶质细胞瘤模型。模型组腹腔注射0.9%氯化钠,治疗组腹腔注射NRP-1 MAb,均每日1次。干预14天后取材。对肿瘤组织称重,免疫组化检测Bax和Bcl-2表达,Western blot检测NRP-1蛋白、Bax蛋白和Bcl-2蛋白表达量,qPCR检测Bax mRNA和Bcl-2 mRNA表达情况,TUNEL检测细胞凋亡情况。结果:假手术组无肿瘤,治疗组肿瘤组织重量显著小于模型组,差异具有统计学意义（P<0.05）。免疫组化显示:与假手术组比较,模型组和治疗组Bax表达显著下降,Bcl-2表达显著上升,差异具有统计学意义（P<0.05）;与模型组比较,治疗组Bax表达上升,Bcl-2表达下降,差异具有统计学意义（P<0.05）。Western blot检测显示:与假手术组比较,模型组和治疗组NRP-1蛋白和Bcl-2蛋白表达量显著上升,Bax蛋白表达量显著下降,差异具有统计学意义（P<0.05）;与模型组比较,治疗组NRP-1蛋白和Bcl-2蛋白表达量显著下降,Bax蛋白表达量显著上升,差异具有统计学意义（P<0.05）。qPCR检测显示:与假手术组比较,模型组和治疗组Bax mRNA表达显著下降,Bcl-2 mRNA表达显著上升,差异具有统计学意义（P<0.05）;与模型组比较,治疗组Bax mRNA表达上升,Bcl-2 mRNA表达下降,差异具有统计学意义（P<0.05）。TUNEL检测显示:与假手术组比较,模型组和治疗组的细胞凋亡率显著上升,差异具有统计学意义（P<0.05）;与模型组比较,治疗组的细胞凋亡率显著下降,差异具有统计学意义（P<0.05）。结论:NRP-1 MAb可通过抑制NRP-1表达而上调Bax蛋白表达,下调Bcl-2蛋白表达促进胶质细胞瘤凋亡。     

香加皮三萜类化合物对实验性大鼠食管癌的阻断作用及机制

目的探讨中药香加皮提取物三萜类化合物（TCCP）对甲基苄基亚硝胺（NMBA）诱导F344大鼠食管癌前病变形成的阻断作用及其机制。方法健康雄性F344大鼠90只,随机分为模型组、TCCP干预组、大豆油对照组和正常对照组。模型组大鼠皮下注射0.5 mg/kg NMBA,TCCP干预组大鼠同时给予0.5 mg/kg NMBA皮下注射及香加皮三萜类化合物20 mg/kg肌肉注每周给药3次,连续5周;大豆油对照组大鼠肌注大豆油1 ml/kg,正常对照组大鼠常规饲养。分别在给药后第9、15和25周,麻醉后解剖大鼠,HE染色后光镜下观察食管上皮组织病理学变化;用Western blot法检测GSK-3β和β-catenin蛋白表达水平;用RT-PCR法检测c-myc mRNA表达水平。结果(1)正常对照组及大豆油对照组在整个实验过程中未发现食管异常变化,模型组大鼠随诱癌时间延长食管病变逐渐加重。TCCP干预可缓解食管上皮的病变。(2)正常大鼠食管上皮中有少量β-catenin蛋白表达,模型组大鼠食管上皮β-catenin蛋白表达显著增强（P<0.05）;正常大鼠食管上皮GSK-3β的蛋白表达丰富,随着诱癌时间延长表达水平逐渐降低;与模型组相比,在诱癌9、15和25周时TCCP干预组大鼠食管上皮组织中β-catenin蛋白表达水平均显著下降（P<0.05）;而GSK3β蛋白表达显著升高（P<0.05）。(3)与正常对照组相比,各时间点模型组大鼠食管上皮c-myc mRNA表达水平均显著升高。与模型组相比,在诱癌9、15周时TCCP干预组大鼠食管上皮组织中c-myc mRNA表达水平均显著下降,而诱癌25周时差异无统计学意义（P>0.05）。结论TCCP可能通过促进Wnt信号分子GSK-3β的表达,抑制β-catenin蛋白的表达,进而下调下游靶基因c-myc的转录,干扰细胞周期转化,逆转细胞的分化,可能是其抑制食管癌变细胞生长机制之一。     

TGF-β1对大鼠脑瘤术后缺氧性脑损伤BAD及Bcl-2 mRNA的影响

目的 观察脑瘤术后大鼠缺氧性脑损伤,外源性转化生长因子β1(TGF-β1)对脑组织BAD及Bcl-2 mRNA表达的影响.方法 40只SD大鼠随机分为假手术组、模型组、生理盐水对照组和TGF-β1干预组,每组10只.建立大鼠脑瘤术后缺氧性脑损伤模型2 h后,侧脑室注入20 ng的TGF-β1,RT-PCR方法检测给药24 h后脑组织BAD及Bcl-2 mRNA表达.结果 模型组及生理盐水组较假手术组,BADmRNA表达显著增高(P《0.05),Bcl-2 mRNA表达降低(P《0.05).TGF-β1干预组较模型组及生理盐水组BAD mRNA表达显著降低(P《0.05),Bcl-2 mRNA表达显著增高(P《0.05).结论 TGF-β1可以通过上调Bcl-2 mRNA表达及下调BAD mRNA表达,抑制细胞凋亡,从而发挥神经保护作用,为TGF-β1临床脑瘤术后缺氧性脑损伤治疗提供理论依据.     

华蟾素对骨癌痛大鼠的镇痛效应及对脊髓胶质细胞活化的影响

目的：探讨华蟾素对骨癌痛大鼠的镇痛效应及对脊髓胶质细胞活化的影响。方法：选用雌性SD大鼠48只,随机分为正常对照组、假手术组（胫骨内注射20 μL PBS）、模型组和华蟾素干预组,每组12只。模型组与华蟾素干预组大鼠胫骨内注射20 μL Walker 256乳腺癌细胞构建骨癌痛模型。华蟾素干预组于造模第7天开始腹腔注射华蟾素注射液,其余各组每天予以等量生理盐水,各组于造模前以及造模后第2、5、7、9、13、15天分别测定热缩足阈值和机械缩足阈值,造模第7天行胫骨X线摄片观察骨质破坏程度,末次行为学检测后处死大鼠,取外周血、L4～L6节段脊髓,利用免疫组化检测星形胶质细胞标记物（GFAP）和小胶质细胞标记物（Iba-1）的表达情况,ELISA检测外周血及脊髓中相关炎性因子（TNF-α和IL-1β）的表达。结果：X线显示模型组大鼠胫骨骨皮质破坏明显、骨质连续性缺乏、骨组织肿胀明显,正常对照组、假手术组未见明显骨组织肿胀、骨连续性较好,提示造模成功。行为学检测结果表明与模型组比较,华蟾素干预可明显缓解骨癌所诱发的机械痛敏、热痛敏（P < 0.01）。免疫组化结果提示与假手术组相比,模型组大鼠脊髓胶质细胞活化明显增强（P < 0.05）;与模型组相比,华蟾素能显著抑制脊髓胶质细胞活化（P < 0.05）。ELISA检测结果显示与假手术组相比,模型组大鼠脊髓及血清中TNF-α和IL-1β表达增强（P < 0.05）;与模型组相比,华蟾素能降低TNF-α和IL-1β表达（P < 0.05）。结论：华蟾素对骨癌痛大鼠有较好的镇痛效应,其镇痛作用可能是通过抑制脊髓星形胶质细胞及小胶质细胞活化发挥作用的。     

阻癌胃泰对大鼠胃癌癌前病变VEGF表达的影响

目的：探讨益气活血中药阻癌胃泰对大鼠胃癌癌前病变血管内皮生长因子（VEGF）mRNA表达水平的影响。方法：MNNG及胃窦部内置弹簧联合诱发胃癌癌前病变模型。．将大鼠随机分为4组,分别为造模对照组、阻癌胃泰治疗组、维酶素治疗组和正常组。取大鼠胃窦部组织送检作病理检测,采用反转录PCR（RT—PCR）技术对各组大鼠的血管内皮生长因子mRNA含量进行测定,用RNA指数（RI）表示。结果：造模大鼠血管内皮生长因子mRNA的RI指数升高,经药物治疗后RI指数下降。阻癌胃泰组与对照组和维酶素组比较均有显著差异（P〈0．05）,中药组与正常组比较无显著性差异（P〉0．05）。维酶素组与对照组比较无显著性差异（P〉0．05）。结论：阻癌胃泰影响胃癌前病变血管内皮生长因子mRNA的表达,可能是其治疗作用的分子机制之一。     

齐墩果酸对酒精诱导的大鼠胃壁氧化损伤的保护作用

目的：研究化学单体齐墩果酸（OA）对酒精诱导的大鼠胃壁损伤的保护作用。方法：采用随机数表法将24只SD大鼠随机分为对照组（等热量葡萄糖溶液）、酒精暴露组（灌胃给予4 g/kg酒精构建酒精性胃壁损伤模型）、OA干预组（灌胃给予溶解了10 mg/kgOA的酒精溶液进行干预），共3组，每组8只，持续30 d。观察OA对酒精诱导的大鼠胃壁损伤是否具有保护作用。检测胃壁大体改变和HE病理变化；胃壁组织丙二醛（MDA）和氧化型谷胱甘肽（GSSG）含量；还原型谷胱甘肽（GSH）含量及GSH/GSSG比值，抗氧化酶转录因子Nrf-2的mRNA和蛋白表达；TNF-α、IL-6的mRNA和蛋白表达水平。结果：与对照组相比，4 g/kg的酒精暴露30 d可以成功诱导大鼠胃壁氧化损伤和炎症反应。与酒精暴露组大鼠相比，OA干预组的胃壁病理损伤程度减轻，胃壁组织MDA、GSSG含量减少（P < 0.05），GSH含量和GSH/GSSG比值增加（P < 0.05），Nrf-2的mRNA和蛋白表达水平显著升高（P < 0.05），同时TNF-α、IL-6的mRNA和蛋白表达降低（P < 0.05）。结论：OA可以通过抗氧化和抗炎作用发挥对酒精诱导大鼠胃壁损伤的保护作用。     

利拉鲁肽对脲链佐菌素诱导阿尔茨海默病大鼠认知功能及Tau蛋白磷酸化的影响

目的：探讨利拉鲁肽对脲链佐菌素（STZ）诱导阿尔茨海默病（AD）大鼠认知功能及Tau蛋白磷酸化的影响。方法：Wistar雄性大鼠24只,随机分为空白对照组、假手术组、模型组和治疗组,每组6只,采用单次右侧脑室注射STZ（3 mg/kg）诱导AD大鼠,14 d后连续4周皮下注射利拉鲁肽干预;利用Morris水迷宫实验检测大鼠认知功能改变,利用免疫组织化学法和Western blot法检测Ser396位点磷酸化的Tau蛋白表达。结果：Morris水迷宫实验结果显示,与空白对照组相比,假手术组大鼠的逃逸潜伏期和穿越平台次数差异无统计学意义（P>0.05）;与假手术组相比,模型组大鼠逃逸潜伏期和穿越平台次数增加（P<0.05）;与模型组相比,利拉鲁肽治疗组大鼠逃逸潜伏期和穿越平台次数减少（P<0.05）。免疫组化和Western blot检测结果显示,模型组大鼠海马组织中Ser396位点磷酸化的Tau蛋白表达增加（P<0.05）,经利拉鲁肽干预后表达减少（P<0.05）。结论：利拉鲁肽能改善STZ诱导的AD大鼠空间学习记忆能力的损伤,降低大鼠海马区Ser396位点磷酸化的Tau蛋白表达。     

Pharmacodynamic model for chemotherapy-induced anemia in rats

Anticancer agents often cause bone marrow toxicity resulting in progressive anemia which may influence the therapeutic effects of erythropoietic-stimulating agents. The objective of this study was to develop a pharmacodynamic (PD) model to describe chemotherapy-induced anemia in rats. Anemia was induced in male Wistar rats with a single intravenous (i.v.) injection of 60 mg/kg carboplatin. Hematological responses including reticulocytes, red blood cells (RBC), hemoglobin, and endogenous rat erythropoietin (EPO) were measured for up to 4 weeks. A catenary, lifespan-based, indirect response model served as a basic PD model to represent erythroid cellular populations in the bone marrow and blood involved in erythropoiesis. The model assumed that actively proliferating progenitor cells in the bone marrow are sensitive to anti-cancer agents and subject to an irreversible removal process. The removal rate of the target cells is proportional to drug activity concentrations and the cell numbers. An additional RBC loss from the circulation resulting from thrombocytopenia was described by a first-order process. The turnover process of rat EPO and EPO-mediated feedback inhibition mechanism regulated by hemoglobin changes were incorporated. Reticulocyte counts decreased rapidly and reached a nadir by day 3 after administration of carboplatin and returned to the baseline by day 13. This was followed by a gradual increase and the rebound peak occurred at about day 15. The hemoglobin nadir was approximately 9 g/dl observed at about 11–13 days compared to its normal value of 13 g/dl and hemoglobin returned to the baseline by day 30. The increase in endogenous rat EPO mirrored inversely hemoglobin changes and the maximum increase was observed soon after the hemoglobin nadir. The carboplatin-treated rats exhibited progressive anemia. The proposed model adequately described the time course of hematological changes after carboplatin in rats and can be a useful tool to explore potential strategies for the management of anemia caused by chemotherapy.     

Involvement of hepcidin in the anemia of multiple myeloma

PURPOSE: Hepcidin is a liver-produced peptide implicated in the anemia of inflammation. Because interleukin (IL)-6 is a potent inducer of hepcidin expression and its levels are elevated in multiple myeloma, we studied the role of hepcidin in the anemia of multiple myeloma. EXPERIMENTAL DESIGN: Urinary hepcidin and serum levels of IL-6, ferritin, C-reactive protein, tumor necrosis factor-alpha, and IL-1 beta were studied in newly diagnosed myeloma patients. In vitro hepcidin induction assay was assessed by real-time PCR assay. RESULTS: Pretreatment urinary hepcidin levels in 44 patients with stage III multiple myeloma were 3-fold greater than normal controls. In the subset of multiple myeloma patients without renal insufficiency (n = 27), a marked inverse correlation was seen between hemoglobin at diagnosis and urinary hepcidin level (P = 0.014) strongly supporting a causal relationship between up-regulated hepcidin expression and anemia. The urinary hepcidin also significantly (P < 0.05) correlated with serum ferritin and C-reactive protein, whereas its correlation with serum IL-6 levels was of borderline significance (P = 0.06). Sera from 14 multiple myeloma patients, with known elevated urinary hepcidin, significantly induced hepcidin mRNA in the Hep3B cells, whereas normal sera had no effect. For 10 patients, the ability of anti-IL-6 and anti-IL-6 receptor antibodies to prevent the serum-induced hepcidin RNA was tested. In 6 of these patients, hepcidin induction was abrogated by the anti-IL-6 antibodies, but in the other 4 patients, the neutralizing antibodies had no effect. CONCLUSIONS: These results indicate hepcidin is up-regulated in multiple myeloma patients by both IL-6-dependent and IL-6-independent mechanisms and may play a role in the anemia of multiple myeloma.     

The effects of erythropoiesis-stimulating agents on the management of chemotherapy-induced anemia and tumor growth in diffuse large B-cell lymphoma patients

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels <10.0 g/dl after a maximum of three R-CHOP cycles and received ≥4 doses of fixed-dose darbepoetin (360 μg) once every 3 weeks. EPOR mRNA was detected in all GCB-DLBCL cell lines, but little/none was detected in ABC-DLBCL cell lines. GCB-DLBCL and ABC-DLBCL cell proliferation was unaffected by EPO or darbepoetin. Rituximab-mediated CDC of DLBCL cell lines with/without EPOR expression was not affected adversely by EPO. In the clinical study, baseline mean hemoglobin was 9.19 g/dl; the overall mean change in hemoglobin was 1.59 ± 1.3 g/dl (16 weeks). Forty-eight percent of enrolled patients achieved a hematopoietic response. Our study shows that ESAs do not affect the growth of DLBCL cells or rituximab-mediated CDC under the experimental conditions that we used, and the appropriate use of ESAs may be effective and safe for DLBCL patients with anemia after R-CHOP.     

Infection of rat liver epithelial cells with v-Ha-ras: correlation between oncogene expression, gap junctional communication, and tumorigenicity

The role of v-Ha-ras oncogene in tumorigenesis in an in vitro/in vivo model system was studied by investigating the expression of the Ha-ras gene, gap junctional intercellular communication, and tumorigenicity as endpoints. Infection of a Fischer 344 rat liver epithelial cell line (WB 344) with a retrovirus containing the v-Ha-ras oncogene resulted in altered cell morphology and decreased contact sensitivity. Gap junctional intercellular communication in v-Ha-ras infected WB cells (WBHa-ras), assessed by fluorescence redistribution after photobleaching (FRAP), microinjection/dye transfer, and scrape-loading/dye transfer techniques, was markedly decreased compared with the level in control WB cells. Injection of 10(7) WBHa-ras cells into the portal vein of male F344 rats caused multiple focal hepatic lesions within 1 and 2 wk, merging to large invading tumors after 3 and 4 wk. Examination of the methylation pattern of the Ha-ras gene in WBHa-ras and control WB cells showed that the infected Ha-ras gene was relatively hypomethylated in comparison to the normal cellular Ha-ras gene, indicating a greater potential for expression. There was an increased level of Ha-ras mRNA in hepatomas as compared with both adjacent nontumor liver tissue and liver tissue obtained from normal animals. Three cell lines derived from three different primary hepatic tumors induced by an injection of WBHa-ras cells in a F344 rat displayed similar growth characteristics, levels of gap junctional communication, and methylation patterns as the original WBHa-ras cells. The results of these studies have established a strong positive correlation between expression of the Ha-ras oncogene, reduced gap junctional intercellular communication, decreased contact sensitivity, and tumorigenicity of the v-Ha-ras-infected rat liver epithelial cells.     

Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration

This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (74 to 202 mU/mL). Five patients (one MM, four small-cell lymphocytic [SCLC] NHL) showed a dramatic increase of hemoglobin (Hb), hematocrit (Hk) and RBC count becoming obvious on the second EPO dose level. Initial ferritin serum values, which were high mostly due to polytransfusion, were significantly reduced in responding patients. Erythropoiesis of one patient with extensive follicular mixed (fm) NHL did not respond to EPO treatment. Platelet (PLT) count increase (greater than 75% above starting levels) during and following EPO therapy was observed in one patient with MM. Adverse events due to EPO therapy have not been recorded. These findings point out a previously unrecognized capacity of EPO given at pharmacologic doses to stimulate erythropoiesis in patients with anemia due to bone marrow infiltration by neoplastic lymphocytes in spite of enhanced endogenous EPO expression.     

腺病毒介导的大鼠增殖抑制基因抑制大鼠胶质瘤的生长

目的:探讨腺病毒介导的大鼠增殖抑制基因(rat hyperplasia suppressor gene,rHSG)对大鼠胶质瘤生长的抑制作用.方法:建立大鼠C6胶质瘤动物模型,分别在接种C6胶质瘤细胞后第4和11天,于肿瘤原位注射0.9％氯化钠溶液(对照组)、重组腺病毒Adv-rHSG-GFP和腺病毒Adv-GFP,并于接种C6胶质瘤细胞后第9、15和21天取脑胶质瘤观察肿瘤的生长情况,免疫组织化学法检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和rHSG蛋白的表达以及微血管密度(microvessel density,MVD),RT-PCR和蛋白质印迹法检测rHSG mRNA及蛋白的表达.结果:Adv-rHSG-GFP组肿瘤体积明显小于对照组和Adv-GFP组(P＜0.01).Adv-rHSG-GFP组PCNA标记指数和MVD均低于对照组和Adv-GFP组.Adv-rHSG-GFP组rHSG mRNA和蛋白的相对表达量均明显高于对照组和Adv-GFP组(P＜0.01).结论:Adv-rHSG-GFP能够抑制胶质瘤血管生成和肿瘤细胞增殖,对恶性胶质瘤的生长具有明显的抑制作用.     

白细胞介素6和hepcidin在弥漫大B细胞淋巴瘤中的表达及其与贫血的相关性

目的：研究白细胞介素6（IL-6）和hepcidin在弥漫大B细胞淋巴瘤（DLBCL）患者中的表达及其在贫血发生中的作用。方法收集诊断时伴或不伴贫血的45例DLBCL患者,在诊断时抽取外周血标本,分别检测IL-6、hepcidin、血清铁蛋白和血红蛋白（Hb）浓度等。以24名健康志愿者作为对照。结果DLBCL患者的血浆hepcidin及IL-6水平分别为（347±171）μg／L、0.27 ng／L（0～9.61 ng／L）,与健康对照者的（175±92）μg／L、0相比,差异均有统计学意义（均P＜0.001）。在高乳酸脱氢酶（LDH）（P＝0.003）、有B症状（P＝0.040）和年龄校正的国际预后指数（IPI）评分＞1（P＝0.010）的患者中血浆hepcidin水平升高,差异均有统计学意义。在男性（P＝0.003）、肿瘤分期Ⅲ～Ⅳ期（P＝0.008）和IPI评分＞1（P＝0.004）的DLBCL患者中IL-6水平升高,差异均有统计学意义。 hepcidin水平与血清铁蛋白高度相关（r＝0.77,P＜0.001）,与IL-6弱相关（r＝0.31,P＝0.030）,与Hb无相关性（r＝-0.12,P＝0.300）。IL-6表达水平与Hb呈负相关（r＝-0.35,P＝0.009）。多因素分析提示,IL-6可以预测贫血（P＝0.03）,而hepcidin不能预测贫血（P＝0.89）。结论 DLBCL患者血浆hepcidin常高表达,但IL-6水平升高在DLBCL患者贫血的发生中起主要作用。     

重组人红细胞生成素治疗放化疗诱发的贫血

[目的]研究重组人红细胞生成素(recombinanthumanerythropoietin,rHuEPO)治疗肿瘤化疗联合体部伽玛刀诱发贫血的疗效及安全性。[方法]45例化疗联合伽玛刀治疗诱发贫血的患者随机分为rHuEPO治疗组和对照组,两组具有可比性。治疗组给予EPO10000U,1次/隔日,皮下注射。连续用药6周,并于用药后1周开始加用硫酸亚铁300mg,口服,3次/日,对照组不给EPO,其它治疗相同。观察EPO对血红蛋白、输血、生活质量的影响及副反应。[结果]治疗组血红蛋白平均提高20.1g/L,而对照组下降9.8g/L(P<0.001)。治疗组KPS评分提高,而对照组则下降。EPO应用副反应少,耐受性好。[结论]摇rHuEPO治疗肿瘤化放疗诱发贫血是一个安全、有效的药物,提高血红蛋白水平,改善生活质量。