氯沙坦对造血祖细胞优势扩增影响的研究  

Study of the effect of Losartan on the advantaged differentiation and proliferation of haematopoietic progenitor

作　　者：张凌云[1] 李荣山[1] 李彩霞[1] 陈娟[1] 白敬恩[1] 

机构地区：[1]山西医科大学第二医院肾内科,太原030001

出　　处：《中国药物与临床》2006年第6期416-419,共4页Chinese Remedies & Clinics

基　　金：山西省自然科学基金资助项目(20051101)

摘　　要：目的探讨氯沙坦[血管紧张素Ⅱ的1型受体(AT1R)拮抗剂]对不同系别造血祖细胞分化的影响及其分子机制。方法由正常脐血分离出的单个核细胞在含不同浓度氯沙坦培养基中悬浮培养,然后转到半固体培养基,观察并计数红系爆式集落形成单位(BFU-E)和粒-单系集落形成单位(CFU-GM),流式细胞仪检测红系和粒系所占比例。巢式反转录聚合酶链反应(nested-RT-PCR)检测AT1R基因的mRNA表达。结果①红系祖细胞在悬浮培养6、9d时检测到AT1R的表达,氯沙坦可阻断此效应。②氯沙坦抑制红系分化,促进粒系分化,且呈浓度依赖性,集落计数结果示其量-效关系为Y=100.125-22.496lgX(X:氯沙坦浓度;Y:红系集落数);Y=220.594+21.882lgX(X:氯沙坦浓度;Y:粒系集落数);流式细胞仪检测示其量-效关系为Y=4296.032-435.335lgX(X:氯沙坦浓度;Y:红系细胞数);Y=5430.975+643.853lgX(X:氯沙坦浓度;Y:粒系细胞数)。③氯沙坦对红系和粒系作用的最适浓度为20nmol/ml。结论氯沙坦能下调AT1R的表达。通过阻断血管紧张素Ⅱ与AT1R的结合,氯沙坦能抑制红系分化,进而使得粒系分化增加。氯沙坦对红系和粒系的作用呈浓度依赖性。Objective To investigate the effect and molecular mechanism of losartan,an ATI-specific antagonist,on the advantaged differentiation of haematopoietic progenitors.Methods Mononuclear cells from normal cord blood were suspension cultured in medium contalnning the losartan of different concentrations.Then cells were transfered to methylcellulose semisolid medium and cultured for fourteen days.The numbers of colony-forming unitgranulocyte -macrophage （CFU -GM） and burst -forming unit -erythroid （BFU -E） colonies were counted . Flowcytometry was used to detect the proportion of erythroid and myeloid.Nested RT-PCR was used to determine the expression of angiotensin Ⅱ type 1 receptor （AT1R）.Results ①AT1R mRNA was detected at day 6 and 9.This expression was blocked by losartan. ②The proliferation of erythroid progenitors was inhibited by losartan while that of myeloid was promoted by it.Those effects were dose-dependent.The regression equations were Y=100.125- 22.496 lgX （X：losartan;Y：number of BFU-E colonies）,Y=220.594＋21.882 lgX （X：losartan;Y：number of CFU-GM colonies）, Y=4296.032-435.335 lgX （X：losartan; Y：number of erythroid）and Y=5430.975＋643.853 lgX（X：losartan; Y：number of myeloid）.③The effects of Losartan were maximal at the concentration of 20 nmol/nd. Conclusion Losartan can down-regulate the expression of AT1R.Losaaan inhibits the proliferation of erythroid progenitors while promotes that of myeloid.Those effects are dose-dependent.

关 键 词：氯沙坦 红系造血 血管紧张素Ⅱ 血管紧张素Ⅱ1型受体拮抗剂 

分 类 号：R965[医药卫生—药理学]