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促红细胞生成素的表达调控机制及其在慢性病贫血治疗中的应用孙士鹏;刘贵建【摘要】促红细胞生成素（EPO）为165个氨基酸残基组成的糖蛋白，主要由胎肝和成人肾皮质的成纤维细胞生成。
EPO的表达受到多种转录因子和表观遗传学调控。
EPO与其受体结合后主要通过激活Jak2／stat5通路，进而激活 Pim、c-Myc、OncostatinM、Bcl-2、Bcl-xL、SOCS 和 D-type cyclin 等基因，在红细胞生成过程中起到抗细胞凋亡和促进细胞增殖等重要作用。
使用促红细胞生成剂上调血红蛋白含量，进而改善贫血患者的能量水平和生活质量具有重要意义，但长期使用存在一些副作用。
本文对EPO表达调控机制及其在贫血治疗中的应用进行论述。
%Erythropoietin (EPO) is a glycoprotein composed of 165 amino acid residue that is mainly produced in the fetal liver and adult kidney cortex fibroblast. The binding of EPO and its receptor can activate Jak2/stat5 pathway. Several important Stat5 target genes, such as Pim, c-Myc, OncostatinM, Bcl-xL SOCS or D-type cyclins are required for functional erythropoiesis. The expression of EPO is regulated by a variety of transcription factors and epigenetic regulation. Erythropoiesis-stimulating agents (ESA) can increase hemoglobin levels, and thus improve the energy level and quality of life in patients with anemia, but the long-term use of ESA also has some side effects. In this paper, the EPO expression regulation mechanism and its application in the treatment of anemia of chronic disease is discussed.【期刊名称】《分子诊断与治疗杂志》【年(卷),期】2014(000)006【总页数】5页(P424-428)【关键词】促红细胞生成素;缺氧;甲基化;贫血【作者】孙士鹏;刘贵建【作者单位】中国中医科学院广安门医院检验科，北京 100053;中国中医科学院广安门医院检验科，北京 100053【正文语种】中文1906年在激素能够通过血液运送到体内较远的组织器官发挥功能的新观点影响下，法国学者Carnot和DeFlandre提出缺氧条件下红细胞生成受到一种激素调控，这种激素命名为促红细胞生成素（erythropoietin，EPO）［1］。
普罗布考对肾脏缺血再灌注损伤大鼠的保护作用及机制杨成;任星峰;彭隽【摘要】目的观察普罗布考对缺血再灌注大鼠肾脏氧化应激损伤的保护作用,同时探讨其作用机制.方法雄性SD大鼠30只,随机分为假手术组(S组)、缺血再灌注组(IR组)、普罗布考治疗组(P+IR组),每组10只.P+IR组大鼠每天用普罗布考(500 mg/kg)灌胃,S组和IR组大鼠每天用等量温开水灌胃.1周后制备肾缺血再灌注大鼠模型:3组大鼠都摘除右肾,IR组和P+IR组用无创动脉夹夹闭左侧肾动脉,30 min 后松夹恢复血流再灌注.再灌注后S组和IR组每天温开水灌胃,P+ IR组每天普罗布考灌胃,连续1周.1周后处死所有大鼠,留取血及肾组织标本,检测大鼠各项血液生化指标,观察肾组织病理学改变.结果与IR组相比,P+IR组血尿素氮(BUN)、血肌酐(SCr)、血脂水平明显降低(均 P<0.05),血清和肾组织中SOD活性明显上升、MDA 含量明显下降(均 P<0.05),肾组织病理损伤减轻,肾指数明显改善(P<0.05).结论普罗布考能提高缺血再灌注损伤大鼠血及肾组织中SOD活性,改善肾功能,降低血脂水平,减轻肾组织病理损伤,发挥肾脏保护作用.%Objective The aim of the study was to investigate the protective effect of probucol on oxidative stress injury in rats with ischemia-reperfusion injury(IRI)and its mechanism. Methods Thirty male Sprague-Dawley rats were randomly di-vided into sham operation group(S group),ischemia-reperfusion group(IR group),and probucol treatment group(probucol+IR group,P+IR group).Rats in the S and IR groups were fed with warm water every day,and rats in P+IR group were treated with probucol.After 1 week,rat model of renal ischemia and reperfusion was established.Right kidneys of the rats were re-moved.In IR and P+ IR groups,the left renal artery was clamped with a non-invasiveartery clamp,and after 30 minutes the blood vessels restored patency by loosening the clamp.After reperfusion,the S and IR groups were perfused with warm water every day,and the P+IR group was treated with probucol for 1 week.After 1 week,all the rats were sacrificed and the blood and kidney tissue specimens were taken.The blood biochemical indexes of the rats were measured,and the pathological changes of the kidneys were observed.Results The levels of blood urea nitrogen(BUN),serum creatinine(SCr)and blood lipids in P+ IR group were significantly lower than those in IR group(all P<0.05);in P+IR group,the level of superoxide dismutase(SOD)in serum and renal tissue was increased significantly(allP<0.05),meanwhile,the levels of malondialdehyde(MDA)were significantly decreased (P<0.05).In P+IR group,the pathological damage of kidney tissue was reduced,and renal index was significantlyimproved(P<0.05).Conclusion Probucol can increase the activity of SOD in blood and kidney of rats with IRI,improve renal function,reduce the level of blood lipids,reduce the pathological injury of renal tissue,and play a role in renal protection.【期刊名称】《华中科技大学学报（医学版）》【年(卷),期】2017(046)006【总页数】5页(P660-664)【关键词】普罗布考;肾脏;缺血再灌注;氧化应激【作者】杨成;任星峰;彭隽【作者单位】中国人民解放军武汉总医院肾内科,武汉 430070;中国人民解放军武汉总医院肾内科,武汉 430070;中国人民解放军武汉总医院肾内科,武汉 430070【正文语种】中文【中图分类】R691.6在日常生活中，各种突发事件、自然灾害以及战争伤导致的多器官损伤中，急性肾损伤(acute kidney injury，AKI)约占67%，其发病率和死亡率一直居高不下。
［文章编号］ １６７１－５８７Ⅹ（２０１２）０５－０９１２－０６［收稿日期］ ２０１１－０９－３０［基金项目］ 重庆市自然科学基金资助课题（ＣＳＴＣ，２００７ＢＢ５２９４）［作者简介］ 邱 炯（１９８０－），女，四川省成都市人，医学硕士，主要从事心血管疾病基础与临床研究。
［通信作者］ 李法琦（Ｔｅｌ：０２３－８９０１１６３５，Ｅ－ｍａｉｌ：ｆａｑｉｌｉ＿２００６＠ｙａｈｏｏ．ｃｏｍ．ｃｎ）促红细胞生成素对心肌缺血再灌注损伤大鼠心肌的保护作用邱 炯１，赵玉伟１，李法琦１，周 平１，李万玉２（１．重庆医科大学附属第一医院老年病科心血管病组，重庆４０００１６；２．重庆医科大学药学院药剂学教研室，重庆４０００１６）［摘 要］ 目的：探讨促红细胞生成素（ＥＰＯ）对心肌缺血再灌注（Ｉ／Ｒ）大鼠缺血及梗死面积的影响，阐明ＥＰＯ对心肌Ｉ／Ｒ损伤的保护作用的机制。
方法：采用在体大鼠心肌Ｉ／Ｒ模型，将２４只健康雄性ＳＤ大鼠随机分为假手术组（ｎ＝８），以６－０号丝线在冠状动脉左前降支下穿过，不予以结扎；Ｉ／Ｒ组（ｎ＝８），以６－０号丝线在冠状动脉左前降支下穿过，并结扎，在结扎线中埋置松解线，４５ｍｉｎ后，松解结扎线，实现再灌注；ＥＰＯ组（ｎ＝８），手术过程同Ｉ／Ｒ组，在再灌注开始即刻，给大鼠腹腔内注射重组人促红细胞生成素（ｒｈＥＰＯ），５ ０００Ｕ·ｋｇ－１。
再灌注２４ｈ后用多导生理仪记录大鼠血流动力学指标，包括收缩压（ＳＰ）、舒张压（ＤＰ）、左室收缩压（ＬＶＳＰ）、左室舒张压（ＬＶＤＰ）、左室舒张末期压（ＬＶＥＤＰ）、心室收缩期室内压上升最大速率（ｄｐ／ｄｔｍａｘ）和心室舒张期室内压下降最大速率（ｄｐ／ｄｔｍｉｎ）的变化；用原位缺口末端标记法（ＴＵＮＥＬ）检测心肌细胞凋亡；用Ｅｖａｎ’ｓ ｂｌｕｅ和氯化三苯基四氮唑（ＴＴＣ）进行心肌染色，测量心肌缺血及梗死范围。
结果：４５ｍｉｎ的缺血和２４ｈ的再灌注血流动力学检测显示，３组大鼠ＳＰ、ＤＰ和ＬＶＳＰ无明显差异（均Ｐ＞０．０５）；与假手术组比较，Ｉ／Ｒ组大鼠ＬＶＤＰ和ＬＶＥＤＰ明显升高，但ｄｐ／ｄｔｍａｘ和ｄｐ／ｄｔｍｉｎ明显下降（均Ｐ＜０．０５）；与Ｉ／Ｒ组比较，ＥＰＯ组ＬＶＤＰ、ＬＶＥＤＰ、ｄｐ／ｄｔｍａｘ和ｄｐ／ｄｔｍｉｎ均有明显改善（均Ｐ＜０．０５）。
