长春新碱对可移植性小鼠淋巴细胞白血病的疗效及其机制研究

目的探讨长春新碱(Vincristine,VCR)对L615白血病的疗效及其可能机制。方法L615白血病造模成功后,分为对照组和VCR组,进行腹腔注射给药(对照组给生理盐水),隔日一次,连续6次。观测小鼠生存时间,体重变化,外周血白细胞计数,肝脾指数,肝脾骨髓涂片及骨髓白细胞分类,流式细胞术测定凋亡率。结果对照组体重明显减轻,VCR组体重无明显改变;VCR组小鼠生存时间是对照组的229%;外周血象,同组小鼠随病程的延长,白细胞逐渐上升,至濒死期则显著上升,与实验前比较有显著差异,且对照组更为显著,而血小板是先升后降,至濒死期,末梢血对照组出现大量L615白血病细胞,占白细胞总数的52.9%,VCR组L615白血病细胞占17.25%,两者具有显著差异(P<0.01);白血病死亡小鼠脾脏指数有差异(P<0.05),且VCR组脾指数大于对照组;流式细胞术证实,VCR能诱导L615白血病体内细胞凋亡,凋亡率达43.81%。结论VCR对L615白血病具有较好的疗效,其机制主要是诱导白血病细胞凋亡;VCR在抗肿瘤的同时,可能对正常组织尤其是免疫系统具有一定的损害作用。

Research on the Curative Effects and Mechanisms of VCR on L615 Leukemia

Objective To discuss the curative effects and the potential mechanisms to the L615 leukemia of VCR.Methods After making the model successfully,put the mice into 2 groups,antitheses one and VCR group.Then carry on the celiac injection(the antitheses one with NS),once every other day,and totally 6 times.Observe the survival time,weight changes,peripheral blood leukocyte count,hepatosplenic index,hepatic,splenic and marrow swears and marrow leukocyte classification and apoptosis rate determined by FCM.Results The antitheses group's weight declined significantly;but no obvious changes in VCR group were observed.The survival time of VCR group was 229% of the antitheses one.For the peripheral blood,with the course of diseases extending,the leukocytes increased and notably in the dying period(notably differences compared with the situation before the experiment,especially in antitheses group);the platelets first increased and then decreased and till the dying period.There were large amount of L615 cells in the peripheral blood of antitheses group(52.9% of the leucocyte number);17.25% in VCR group was L615 cells,but there were still great differences between the two groups(P<0.01).The splenic indexes of the dead mice were different(P<0.05),and that of VCR group was greater.FCM proved that VCR induced the apoptosis of L615 cells in vivo,and the rate reached to 43.81%.Conclusion VCR has good curative effects on L615 leukemia.To induce the apoptosis of leukemia cells is its main mechanism.It may damage the normal tissues,especially the immune system when it is repelling the tumor.