黄连解毒汤通过抑制血红素加氧酶-1发挥逆转慢性粒细胞白血病加速期的作用

目的:探讨黄连解毒汤(HLJDT)对慢性粒细胞白血病(CML)加速期的治疗作用,以及HLJDT及其主要活性成份之一的黄芩素对血红素加氧酶-1(HO-1)表达的影响。方法:通过对1例CML的患者口服HLJDT治疗6个月的观察,外周血检查和骨髓穿刺分析治疗前后外周血象和骨髓象的变化;流式细胞术分析HLJDT和黄芩素对CML细胞系K562的活细胞计数的影响;逆转录多聚酶链反应(RT-PCR)检测患者骨髓单个核细胞HO-1基因的表达;蛋白印记检测经黄芩素处理后K562细胞HO-1蛋白的表达水平。结果:口服HLJDT对CML加速期的治疗有效,可明显降低骨髓和外周血原始粒细胞和早幼粒细胞数,使疾病重新回复到慢性期;并且在体内能降低肿瘤细胞HO-1基因的表达,在体外,HLJDT能抑制K562细胞的增殖,且其主要成份黄芩素亦有相同作用,并且下调HO-1蛋白的表达。结论:HLJDT具有治疗CML加速期的作用,其机理与抑制HO-1基因和蛋白的表达有关;因此,HLJDT具有潜在的临床应用价值。

HLJDT Reverses Chronic Myelogenous Leukemia in Accelerated Phase via Down-Regulation of Hemo Oxygenase-1 Gene Expression

Objective:To explore the effects of Huang-Lian-Jie-Du-Tang (HLJDT),a traditional Chinese medicine with a main component of baicalein,on chronic myelogenous leukemia (CML) in accelerated phase,and the inhibitory effects of HLJDT and baicalein on heme oxygenase-1 (HO-1) expression. Methods:Oral HLJDT was taken daily for half a year for the treatment of one CML patient in accelerated phase. The blood smear and bone marrow aspiration were examined before and after HLJDT administration. Flow cytometry was used to determine the viable cell number induced by HLJDT or baicalein,in K562 cell line. RT-PCR was used to detect HO-1 gene expression affected by HLJDT in bone marrow mononuclear cells. Western blot was used to examine the HO-1 protein expression affected by baicalein in K562 cells. Results:HLJDT could reverse CML from accelerated phase to chronic phase,down-regulate HO-1 gene expression in bone marrow mononuclear cells,and inhibit K562 cell proliferation. It was further found that baicalein could suppress the proliferation of K562 cell and their HO-1 protein expression. Conclusion:HLJDT has ability to reverse accelerated CML in accelerated phase maybe through the down-regulation of HO-1 gene and protein expression by baicalein. Thus,HLJDT may have a potential in the treatment of patients with CML in aggressive phases.