目的:多发性骨髓瘤(Multiple Myeloma,MM)患者约有80%伴有贫血,临床上多数患者以输血方式纠正贫血。重组人促红细胞生成素(recombinant human erythropoietin, rHuEPO)用于治疗MM患者的贫血尽管有效,但以何等剂量、应用多长时间疗效较佳尚无定论。目的: 观察持续使用大剂量rHuEPO对MM患者贫血的纠正作用及效果。方法:87例诊断明确的多发性骨髓瘤伴有贫血的患者,开始连续每天使用重组人促红细胞生成素4万单位,皮下注射,共5d;以后每周使用一次,每次4万单位皮下注射,间断补充铁剂。对照组90例选自同期住院的诊断明确的多发性骨髓瘤患者,当其贫血症状明显时或血红蛋白水平低于60 g/L时,给予输血纠正其贫血,使多数患者血红蛋白水平维持在80 g/L～100 g/L以上。两组患者化疗方案不做特殊规定,整过研究观察期6月。结果: rHuEPO组在使用rHuEPO后2周其血红蛋白开始上升,中位反应时间16d;1月半至2月血红蛋白可升至正常水平,达正常血红蛋白水平的中位时间51d。进入研究后3月和6月时,rHuEPO组生活幸福感指数(INLH)明显优于输血组,分别为6927±318(Plt;005)和7216±283(Plt;001)与5835±289和5776±324。6月后,rHuEPO组平均每例直接费用成本1075440元,明显低于输血组需要达到同样效果所需的每例2070420元。结论:大剂量rHuEPO治疗MM相关性贫血优于输血,其起效快、疗效好,患者生活幸福感改善明显,费用成本低,安全性较好。
目的:研究低氧性肺动脉高压大鼠对实验性红细胞增多的适应。方法:健康SD大鼠28只,体重200～250 g,随机分为4组:常氧对照组（N）、单纯低氧组（H）、低氧+低剂量人重组促红细胞生成素（rEPO） 600 u/kg（H+E1）组、低氧+高剂量rEPO 1200 u/kg（H+E2）组,每组7只大鼠。除常氧对照组外各低氧组大鼠均缺氧21 d,每日8 h。其中后两组每周腹部皮下注射不同剂量的rEPO三次。取血样测定红细胞数、全血粘度及红细胞变形指数；颈外静脉插管测定平均肺动脉压力；光镜观察反映肺动脉重构程度的形态学参数肺小动脉管壁厚度百分比、肺非肌性小动脉肌化程度。结果:①随着rEPO注射剂量的增加,红细胞、全血粘度有不同程度的增高；②全血粘度增高的同时红细胞变形指数也相应地增加；③随着rEPO剂量的增加,平均肺动脉压力逐渐增高,但是肺血管重构程度反而有所缓解。结论:实验性红细胞增多通过改变红细胞变形性和缓解肺血管重构程度来阻遏低氧性肺动脉高压的进一步发展。
Objective To investigate the effects of recombinant human erythropoietin ( rHuEPO) on expressions of Bax and Bcl-2 proteins in hyperoxia-induced lung injury of adult rats. Methods Fortyeight healthy male SD adult rats were randomly divided into six groups. The control group ( 0 h) breathed with room air. The rHuEPO intervention group was put into oxygen chamber and breathed with 100% O2 for 96 h plus intraperitoneal injection of rHuEPO (1000 U/kg) daily. Other four groups were put into oxygen chamber and breathed with 100% O2 for 24, 48, 72 and 96 h respectively. Arterial blood gases were measured to calculate oxygenation index. Wet-to-dry weight ratios of left lung were measured. The contents of TNF-α and IL-1β in bronchoalveolar lavage fluid (BALF) were assayed with radioimmunoassay. The expressions of Bax and Bcl-2 proteins in the lung were determined withWestern blot and immunohistochemisty. The changes of lung histopathology were assessed by hematoxylin and eosin stain and observed under light microscope. Results After breathing 100% O2 , the oxygenation index decreased gradually and reached minimal value at 96 h. The wet-to-dry weight ratio of left lung increased gradually and reached maximal value at 96 h. The contents of TNF-α and IL-1β in BALF reached maximal value at 48 h and then decreased gradually. The expression of Bax protein increased, but the expression of Bcl-2 protein decreased gradually in the lung. Compared with the 96 h group, the oxygenation index was higher, wet-to-dry weight ratio and contents of TNF-α and IL-1β in BALF decreased, the expression of Bax protein decreased, and the expression of Bcl-2 protein increased in the lung of the rHuEPO group. Conclusion rHuEPO can attenuate hyperoxia-induced lung injury of adult rats by down-regulating expression of Bax protein and up-regulating expression of Bcl-2 protein.
目的 通过比较三种血液净化方式对炎症介质、甲状旁腺激素等中大分子毒素的清除效果，并观察促红细胞生成素（EPO）的治疗效果，探寻有利于肾性贫血改善的最佳透析模式。 方法 2011年5月－8月采用前瞻性、随机对照、开放式设计，选择维持性血透患者60例，随机分成3组，每组20例。血液灌流（HDP）组[每2周5次血液透析（HD）+1次HDP]、血液透析滤过治疗（HDF）组（每2周5次HD+1次HDF）、HD组（每2周6次HD），随访3个月。检测试验前后反应蛋白（CRP）、β2微球蛋白、甲状旁腺素（PTH）、白介素-6的水平以及各组患者肾性贫血指标的变化。 结果 3个月试验结束时，HDP组和HDF组4项尿毒症毒素水平均显著下降，其中HDP组CRP水平明显低于HDF组（P＜0.05）；HDP组和HDF组试验后的血红蛋白水平较试验前升高，ERI值下降。HD组试验前后的毒素水平无明显变化，ERI值升高。3组患者均未出现严重不良事件。 结论 HDP和HDF清除中大分子毒素的能力优于HD，有利于缓解微炎症状态，改善EPO治疗效果。HDP和HDF的远期效果哪种更好，尚有待于进一步的研究。
Erythropoietin （EPO） is known as a classical hematopoietic growth factor, which has been used to treat anemia caused by different reasons. In recent years, EPO＇s non-hematopoietic biological effects have gradually become a focus. Among these effects, EPO＇s tissue protection is most attractive and EPO has been proved to protect many different tissues and organs. Myocardial protection has always been the important and key topic in the field of cardiovascular diseases. Reports about EPO＇s myocardial protective effects have been published in the recent two years, which direct the research about myocardial protection with new ideas. In this article, the discoveries and unsolved problems associated with EPO＇s myocardial protection were reviewed.
ObjectiveTo study the differentially expressed proteins of recombinant human erythropoietin (r-HuEPO) in hippocampus of Pentetrazol (PTZ) -induced epileptic rats, and to provide a basis for exploring the pathogenesis of epilepsy and seeking new therapeutic targets. Methods Twelve 6~8-week-old Sprague Dawley rats that weighted 230~250 g were randomly divided into two groups: PTZ group, PTZ+ EPO group. The differential proteins of recombinant human EPO in hippocampus of pentylenetetrazole-induced epileptic rats were analyzed and identified by TMT technique based on mass spectrometry.Results 139 differentially expressed protein sites were detected in hippocampal tissues of epileptic rats, of which 55 were up-regulated and 84 down-regulated. Conclusion Recombinant human erythropoietin can inhibit many differentially expressed proteins in the hippocampus of pentaerythraze-induced eclampsia rats by upregulation of Isocitrate dehydrogenase (NADP), Reduced nicotinamide purine dinucleotide phosphate (NADPH), Thioredoxin reductase 2 mitochondrial (TrxR), reduce nerve cell damage.
Objective To investigate the effect of exogenous erythropoietin (EPO) on the denervated muscle atrophy. Methods Twenty-four SD male rats, weighting 200-220 g were made the models of denervated gastrocnemius muscle after sciatic nerves were transected under the piriform muscle at the right lower leg, and were randomly divided into two groups (n=12). rhEPO (2 500 U/kg) was injected daily into the denervated gastrocnemius muscle in EPO group, and normal sal ine was injected into the denervated gastrocnemius muscle in control group. To observe the general state of health of the experimental animal, the muscle wet weight, the muscle cell diameter, the cross section area, the protein amount, thepercentage of the apoptotic muscle cells, and the Na+-K+-ATPase and Ca2+-ATPase activities were measured 2 and 4 weeks after operation. Results All experimental animals were survived during experiment without cut infection, and all animals could walk with pull ing the right knee. At 4 weeks after operation, 7 cases showed ulcer in the right heel, inculding 5 in the control group and 2 in the EPO group. At 2 and 4 weeks after operation, the muscle wet weight in EPO group was (885.59 ± 112.35) and (697.62 ± 94.74) g, respectively; in control group, it was (760.63 ± 109.05) and (458.71 ± 58.76) g, respectively; indicating significant differences between two groups (P lt; 0.01). The protein amount in EPO group was (77.37 ± 5.24) and (66.37 ± 4.87) mg/mL, respectivly；in control group, it was (65.39 ± 4.97) and (54.62 ± 6.32) mg/mL；indicating significant differences between two groups (P lt; 0.01). At 2 and 4 weeks after operation, the myofibrillar shapes were nearly normal in EPO group while there were muscle fiber atrophy, some collapse and obviously hyperblastosis between muscle bundle. There were significant differences in the muscle cell diameter and the cross section between two groups (P lt; 0.01). However, the percentage of the apoptotic muscle cells was 11.80% ± 1.74% and 28.47% ± 1.81% in control group, respectively, which was significantly smaller than that in EPO group (21.48% ± 2.21% and 55.89% ± 2.88%, P lt; 0.01). At 2 and 4 weeks after operation, Na+-K+-ATPaseand Ca2+-ATPase activities in EPO group were higher than those in control group (P lt; 0.01). Conclusion EPO can delay the denervated muscle atrophy.
ObjectiveTo investigate the effect of recombinant adenovirus-mediated bone morphogenetic protein 9 (BMP-9) and erythropoietin (EPO) genes co-transfection on osteogenic differentiation of adipose-derived stem cells (ADSCs) in vitro. MethodsThe inguinal adipose tissue was harvested from 4-month-old New Zealand rabbits, ADSCs were isolated with enzyme digestion and adherence method, and multipotent differentiation capacity was identified. The 3rd generation ADSCs were divided into 5 groups: normal cells (group A), empty plasmid control group (group B), BMP-9 or EPO recombinant adenovirus transfected cells (groups C and D), BMP-9 and EPO recombinant adenovirus co-transfected cells (group E). The inverted phase contrast microscope was used to observe the cell growth at 7 days; the expression of cell fluorescence was observed under a fluorescence microscope at 14 days, and viral transfection efficiency was calculated at 48 hours; Western blot was used to detect the expressions of BMP-9 and EPO proteins at 14 days. The expression of alkaline phosphatase (ALP) activity was detected at 3, 7, and 14 days after osteogenic induction, and alizarin red staining was used to detect calcium nodules formation and real-time fluorescence quantitative PCR to detect the expressions of osteopontin (OPN) and osteocalcin (OCN) at 3 weeks. ResultsAt 7 days after transfected, some cells showed oval, round, and irregular shape under the inverted phase contrast microscope in groups A and B; a few fusiform cells were observed in groups C and D; oval cells increased obviously, and there were only few round cells in group E. The fluorescence microscope observation showed that BMP-9 and EPO, BMP-9/EPO recombinant adenovirus could stably transfected ADSCs, with transfection efficiency of 80%-93%. The expressions of BMP-9 and EPO proteins significantly higher in group E than the other groups by Western blot (P < 0.05). The ALP activity significantly increased in group E when compared with that in the other groups at 3, 7, and 14 days after osteogenic induction (P < 0.05); the number of calcium nodules in group E was significantly more than that in the other groups (P < 0.05). Real-time fluorescence quantitative PCR showed that OPN and OCN genes expressions were significantly higher in group E than other groups (P < 0.05), and in groups C and D than groups A and B (P < 0.05). ConclusionRecombinant adenovirus-mediated BMP-9 and EPO genes can transfect ADSCs, which can stably express in ADSCs, BMP-9/EPO genes co-transfection can more promote the expressions of osteoblast-related genes and protein than non-transfected and single gene transfection.
【摘要】 目的 比较生血宁片和多糖铁复合物胶囊两种口服铁剂在治疗维持性血液透析患者肾性贫血中的治疗效果。 方法 2008年12月-2010年6月间选择40例维持性血液透析贫血患者，随机分为生血宁片组和多糖铁复合物胶囊组，每组20例，观察期为8周。分别检测两组患者用药前及用药后4、8周时血红蛋白、红细胞压积、血清铁蛋白、转铁蛋白饱和度等指标情况。同时两组患者均使用基因重组人促红细胞生成素，按100~120 U/（kg·周），分两次皮下注射。 结果 治疗前两组指标无明显差异，治疗后两组患者的血红蛋白、红细胞压积、血清铁蛋白以及转铁蛋白饱和度较治疗前均显著上升，且两组患者升高的幅度相比，生血宁组升高的幅度更显著。治疗结束时，两组患者不良反应方面的差异无统计学意义。 结论 两种口服铁剂均能有效地纠正血液透析患者的铁缺乏及贫血状况；生血宁片组的作用更显著，且还具备降低患者促红细胞生成素使用量的作用。【Abstract】 Objective To compare the effect of Shengxuening piece and capsule polysaccharide-iron complex on anemia in hemodialysis patients. Methods A total of 40 patients with anemia in maintenance hemodialysis treated between December 2008 and June 2010 were randomly divided into Shengxuening piece group and capsule polysaccharide-iron complex group; the patients were observed for 8 weeks. Hemoglobin (Hb), hematocrit (Hct), serum ferritin (SF), transferrin saturation (TSAT) and other indicators were detected before treatment four and eight weeks after the treatment. While patients were used recombinant human erythropoietin (EPO) according to 100-120 U/(kg·week), twice subcutaneous injection. Results Before treatment, there was no significant difference between the two groups. Hb, Hct, SF and TSAT increased significantly after treatment in both of the groups and specially in the Shengxuening piece group. After the treatment, the difference in the adverse reaction between the two groups was not significant. Conclusions Both oral iron can effectively correct the hemodialysis patients with iron deficiency and anemia. However, Shengxuening has more significant role and may reduce the use of erythropoietin in patients with hemodialysis.