摘要
采用体外微量克隆培养体系研究了组胺Ｈ＿２受体激动剂４－甲基组胺（４－ＭＨ）和拮抗剂雷尼替叮（ｒａｎｉｔｉｄｉｎｅ）及抗癌药阿糖胞苷分别对正常人外周血粒－巨噬系祖细胞（ＰＢＣＦＵ－ＧＭ）和ＨＬ－６０白血病细胞生长的作用。当４－ＭＨ的浓度为１０￣（－９）～１０￣（－６）ｍｏｌ·Ｌ￣（－１）时，可促进ＰＢＣＦＵ－ＧＭ的增殖，４－ＭＨ的浓度增加至１０￣（－１）ｍｏｌ·Ｌ￣（－１）时则表现为抑制ＰＢＣＦＵ－ＧＭ的增殖。Ｒａｎｉｔｉｄｉｎｅ的浓度为１０￣（－９）～１０￣（－５）ｍｏｌ·Ｌ￣（－１）时，表现出对ＰＢＣＦＵ－ＧＭ增殖的抑制作用，但在１０－６ｍｏｌ·Ｌ￣（－１）剂量时对ＰＢＣＦＵ～ＧＭ的抑制率低于５０％，而在该剂量时对ＨＬ－６０白血病细胞的抑制率已达１００％，具有一定的选择性。抗癌药阿糖胞苷（Ａｒａ－Ｃ）对ＨＬ－６０白血病细胞的抑制作用比对ＰＢＣＦＵ－ＧＭ的抑制作用较强，但两者的ＩＣ＿（５０）值处于同一个数量级。在强化化疗剂量１０￣（－５）ｍｏｌ·Ｌ￣（－１）时，Ａｒａ－Ｃ对ＨＬ－６０白血病细胞和ＰＢＣＦＵ－ＧＭ正常造血祖细胞的抑制率均达１００％。
Colony forming unit of granulocytes and macrophages from peripheral bloed(PBCFU-GM)represents stem and/or progenitor cells from human blood,In this paper,the effects ofhistamine H2 receptor agonist 4-methylhistamine(4-MH)and its antagonist ranitidine(Ranit) on thegrowth of PB CFU-GM cultured in methylcellulose system were studied and their differential effects onnormal PB CFU-GM and leukemic HL- 60 cells were compared with the effect of the antineoplasticagent cytosine arabinoside(Ara- C). It was found that the histamine H2 receptor agonist 4-MHstimulated the growth of PB CFU-GM when 4- MH was added at the concentrations from 10-9mol·L-1 to 10-6 mol·L-1 among which the dose 10-8 mol·L-1 exerted most potent stimulatingeffect(the PB CFU-GM colony numbers was 137.68%±8. 20%、vs the control,P<0. 01).Incontrast, the antagonist Ranit showed inhibitory effect on the growth of PB CFU-GM when at theconcentrations 10-9～10-5 mol·L-1 cultured for 14d in the same methylcellulose system, Theinhibition rate was 23.73%±1. 16%(10-9 mol·L-1) and 41.42%±6.75%(10-6 mol·L-1),respectively.Although both Ranit and Ara-C could inhibit the growth of PB CFU-GM in vitro, Ranitexerted much greater inhibition on HL-60 leukemic cells than on normal PB CFU-GM at the dose of10-6 mol·L-1( 100% inhibition for HL-60 and<50% inhibition for PB CFU-GM).However,the inhibition rate of Ara -C for both HL-60 and PB CFL-GM was 100% at the intensivechemotherapeutic dose of 10-5 mol·L-1. It would appear that the histamine H2 receptor agonist 4-MH possesses stimuiating effect on thegrowth of PB CFU-GM similar to its effect on CFU-GM frorn bone marrow as documented before,Itis suggested that the histamine H2 receptor antagonist Ranit has,to some extent,potential in thetreatment of myeloid leukemia,especially when combined with antineoplastic agent Ara -C atsuboptimal doses.
出处
《药学学报》
CSCD
北大核心
1996年第5期340-345,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金
关键词
组胺H2
受体激动剂
受体拮抗剂
白血病
抗癌药
Histamine H2 receptor agonist
Histamine H2 receptor antagonist
Hematopoieticprogenitor
HL-60 leukemia cell
Antineoplastic agent
