预防性糖皮质激素对实体瘤患者化疗后粒细胞减少的影响及机制

The effect and mechanisms of post-chemotherapy granulopenia by prophylactic use of glucocorticoid in patients with solid tumor

目的研究预防性糖皮质激素的使用对实体瘤患者化疗后粒细胞减少的影响及机制。方法按照使用糖皮质激素与否,将39例患者分为激素组(20例)和非激素组(19例),采用Annexin-Ⅴ/PI方法检测化疗前(第1天)、化疗后(第6天)外周血粒细胞凋亡,同时检测粒细胞表面Fas的表达,并观察它们与粒细胞数目变化的关系。结果 (1)激素组化疗后粒细胞Fas表达高于化疗前(P<0.05),粒细胞计数、凋亡率差异前后未见统计学意义;非激素组化疗后粒细胞计数低于化疗前,凋亡率、Fas表达均高于化疗前,差异可见显著性差异(P<0.05)。(2)化疗前中性粒细胞计数与凋亡率负相关(r=-0.370,P=0.020);非激素组化疗后中性粒细胞凋亡率与Fas表达正相关(r=0.518,P=0.023)。(3)激素组、非激素组第6天粒细胞下降的患者分别为45%(9/20)、89.5%(17/19);而第8天粒细胞下降的患者分别为50%(10/20)、100%(19/19);激素组粒细胞下降的患者比例均低于非激素组(P<0.05)。结论糖皮质激素可以影响化疗药物对中性粒细胞的凋亡诱导作用,抑制中性粒细胞减少的发生,这个作用可能不全是通过Fas途径诱导凋亡导致的。临床上使用糖皮质激素的化疗患者粒细胞减少的规律不同于未用激素者。

Objective To investigate the effect and mechanisms of post-chemotherapy granulopenia by prophylactic use of glucocorticoid(GC)in patients with solid tumor.Methods The patients were divided into GC group(20 cases)and non-GC group(19 cases)according to using GC whether or not.Apoptosis and surface Fas expression of granulocytes in peripheral blood were detected using annexin-Ⅴ/propidium iodide(PI)stainingand and Fas fluorescent antibody at pre-chemotherapy(the first day durante chemotherapy)and post-chemotherapy(the sixth day durante chemotherapy),and to observe relation between them and change of granulocyte counts.Results(1)The surface Fas expressed intensity at post-chemotherapy was higher than it at pre-chemotherapy in GC group(P<0.05),the difference of the proportion of apoptosis between them had not statistical significance.The mean of granulocyte at post-chemotherapy was lower than it at pre-chemotherapy(P<0.05).The proportion of apoptosis and surface Fas expressed intensity of granulocytes at post-chemotherapy was higher than it at pre-chemotherapy in non-GC group(P<0.05).(2)There was negative correlation between granulocyte counts and the proportion of apoptosis at pre-chemotherapy(r=-0.370,P=0.020).There was positive correlation between the proportion of apoptosis and surface Fas expressed intensity at post-chemotherapy in non-GC group(r=0.518,P=0.023).(3)The proportion of patients with granulocyte counts decreased at the sixth day in GC group and non-GC group was 45%(9/20),89.5%(17/19)respectively,them at the eighth day was 50%(10/20),100%(19/19)respectively.The proportion in GC group was lower than it in non-GC group(P<0.05).Conclusions Prophylactic use of GC may exert an effect on apoptosis induction by chemotherapeutics,delay the appearance of granulopenia.The induction may be not incriminate Fas pathway fully.The rule of granulopenia in patients with chemotherapy used of GC may be different with it in patients not used of GC in clinically.