葛根素注射液致体内外溶血反应及其机制研究

目的:探讨葛根素注射液可能引起的溶血反应及其机制。方法:采用人红细胞进行体外溶血性实验;KM小鼠进行体内实验,设80、160mg/kg葛根素注射液和5%葡萄糖组,小鼠尾静脉给药7d/周期,停药5d,给药4个周期。于给药前、每周期末次给药后,进行溶血和血液指标检测,以确定发生溶血的小鼠。对发生溶血的小鼠测定其红细胞渗透脆性范围和膜胆固醇(Ch)、磷脂(Pl)含量,进行直接抗球蛋白试验(DAT),显微镜观察肝、肾组织结构。结果:所用葛根素注射液未引起人红细胞体外溶血反应;在动物第4个周期给药后,80mg/kg组有2只(6.67%)小鼠表现溶血反应,其粪隐血实验阳性,红细胞数、血红蛋白值降低,网织红细胞数增多;肝、肾组织结构发生病理改变。与5%葡萄糖组相比,溶血小鼠红细胞渗透脆性范围、膜Ch/Pl比值未见异常,DAT实验IgG(+)。160mg/kg组小鼠均未发生溶血反应。结论:所用葛根素注射液未引起人红细胞体外溶血;反复给药可致小鼠偶发溶血,但与剂量无关;其溶血发生机制与红细胞膜渗透脆性和流动性无关,与IgG型免疫应答有关。

Study on mechanism of hemolysis induced by puerarin injection

Objective:To study the mechanism of the hemolysis induced by puerarin injection.Method:The hemolysis of the human erythrocytes was detected in vitro.Mice were used in vivo tests as follows:80 mg/kg,160 mg/kg puerarin injection and 5% glucose injection.Mice were administrated with puerarin injection through the caudal vein for 7 days every cycle,interval 5 days,starting another cycle.Erythrocytes,reticulocytes,hemoglobin and the stool occult blood test were measured before the test and after every cycle.After 4 cycles,the histopathologic examination of liver and kidney was performed.The osmotic fragility and Ch/Pl of erythrocytes were determined,and direct antiglobulin test(DAT) was performed.Results:The puerarin injection used in the test had not induced the hemolysis of human erythrocytes in vitro,but induced hemolysis of 6.7% mice of 80 mg/kg puerarin injection.Erythrocyte and hemoglobin of the hemolyzed mice were obviously declined,while reticulocyte was increased,the stool occult blood test was positive,the histopathologic examination showed that the liver and kindey had been injured.Compared with 5% glucose injection,the osmotic fragility,Ch/Pl of erythrocytes of the hemolyzed mice were normal,but DAT of rabbit anti-mouse IgG were positive,which indicated that immunologic response was involved.Hemolysis was not occured with the mice of 160 mg/kg puerarin injection.Conclusions:Puerarin injection used in the test did not induce the hemolysis of the human erythrocytes,but it induced the hemolysis of the mouse through administration repeatedly.The mechanism of the hemolysis was correlation with immunologic response.