Cimetidine对小鼠低氧条件下红系造血增强的抑制作用

INHIBTTIRY EFFECT OF CIMETIDNE ON ENHANCED ERYTHROPOIESIS OF MOUSE EXPOSED TO HYPOXIA

本实验以组按H_2受体拮抗剂甲氰咪胍(Cimetidine)处理低压(0.5大气压)条件下生活的LACA小鼠。观察到:低氧两周后外周RBC数、PCV、Hb骨髓CFU-E数和BFU-E数明显增多,且CFU-E和BFU-E集落较大(集落直径为正常对照的3～5倍,资料未录入);外周血WBC数及骨髓CFU-GM数明显减少。CFU-S向红系分化明显增多,向巨核系、粒系分化明显减少。低氧小鼠同时给予Cimetidine两周后与低氧对照组比较,外周血RBC数、PCV、Hb、CFU-E数、BFU-E数均明显减少。外周血WBC数和Pt数在Cimetidine低剂量组(1mg/天)升高,但随着剂量的增加又有降低趋势(无统计学意义)。Cimetidine使CFU-GM数较低氧对照组明显增多,但随着剂量的增加CFU-GM增多的幅度逐渐减少。高浓度的Cimetidine(2-4mg/天)使CFU-S数较低氧对照组明显减少。CFU-S在Gmetidine的作用下向红系分化明显减少。而向粒系和巨核系的分化相对增多。

LACA mice were injected with cimetidine,an antagonist of histamine H_2 receptor,for 14 days while the mice living at altypobaric(0. 5 atmosphere)chamber. Results showed that an increase in RBC counts. PCV value, hemoglobin concen- tration,the numbers and sizes(3~5 fold colony diameter of control, data not shown) of CFU-Eand BFU-E;a decrease in WBC and numbers of marrow CFU-GM;an increase in CFU-S differentiation toward erythroid cell line;a decrease in CFU-S differentiation toward megakaryoid and granuloid cell lines after hypoxia. After treatment of hypoxia and cimetidine,RBC counts, PCV,Hb concentration,numbers of CFU-E and BFU-E were decreased significantly; the pe- ripheral WBC counts were increased at lower concentration (1mg/day)of cimetidine, but showing the tendency to decrease as proliferation was enhanced strikingly by cimetidine as conpared with that of hypoxic control,but the enhancing effect reduced gradually as cimetidine dosage increasing. Cime(?)dine at higher concentration reduced the number of CFU-S sig- nificantly. Under the influnce of cimetidine, the differentiation of CFU-S toward erythroid cellline was dacreased, but the differentiation toward granuloid and megakaryoid cell lines was relatively increased.