茵栀黄口服液与金银花提取物对葡萄糖-6-磷酸脱氢酶缺乏大鼠的溶血影响及退黄疗效分析

Effects of Yinzhihuang oral liquid and Lonicera japonica extract on hemolysis and hyperbilirubinemia in rats with glucose-6-phosphate dehydrogenase deficiency

摘要:

目的 研究不同剂量茵栀黄口服液与不同浓度金银花提取物对葡萄糖-6-磷酸脱氢酶（G6PD）缺乏大鼠的溶血影响和退黄疗效比较。方法 将实验用雄性Wistar大鼠随机分为10组，每组10只，分别为正常组（不予任何处理）、阴性对照组（给予生理盐水）、阳性对照组（给予伯氨喹啉）、2倍剂量茵栀黄组（给予13.4 mL/kg茵栀黄口服液）、4倍剂量茵栀黄组（给予26.8 mL/kg茵栀黄口服液）、8倍剂量茵栀黄组（给予53.6 mL/kg茵栀黄口服液）、正常浓度金银花组（给予剂量为6.7 mL/kg，浓度为8 mg/mL金银花提取物）、中浓度金银花组（给予剂量为6.7 mL/kg，浓度为40 mg/mL金银花提取物）、高浓度金银花组（给予剂量为6.7 mL/kg，浓度为80 mg/mL金银花提取物）、极高浓度金银花组（给予剂量为6.7 mL/kg，浓度为160 mg/mL金银花提取物）。除正常组外，其余各组通过乙酰苯肼制造G6PD缺乏大鼠模型，通过瑞氏染色观察造模前后大鼠红细胞形态变化；造模后各组给予相应药物进行处理，用血常规及血生化检测仪检测相关溶血指标，以及血总胆红素和间接胆红素水平。结果 G6PD缺乏大鼠红细胞形态不规则，中央区染色变浅。与造模前相比，阳性对照组给药后红细胞计数下降，游离血红蛋白水平和网织红细胞百分比均上升（P < 0.05）；不同剂量茵栀黄组和不同浓度金银花组只有网织红细胞百分比均高于造模前水平（P < 0.05）。不同剂量茵栀黄组总胆红素和间接胆红素水平均较阳性对照组下降（P < 0.05），不同浓度金银花组间接胆红素水平低于阳性对照组（P < 0.05），但总胆红素水平高于各剂量茵栀黄组（P < 0.05）。与4倍剂量和8倍剂量茵栀黄组相比，2倍剂量茵栀黄组给药后大鼠总胆红素水平下降百分比最高（P < 0.05）。结论 大剂量茵栀黄口服液与不同浓度金银花提取物均不会引起G6PD缺乏大鼠发生溶血；茵栀黄口服液退黄疗效比金银花提取物好，且其疗效可能并不随剂量增大而提高。

Abstract:

Objective To investigate the effects of different doses of Yinzhihuang oral liquid and different concentrations of Lonicera japonica extract on hemolysis and hyperbilirubinemia in rats with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Methods Male Wistar rats were randomly divided into 10 groups (n=10 each):normal control group (untreated), negative control group (saline-treated), positive control group (primaquine-treated), low-, medium-and high-dose Yinzhihuang oral liquid groups (13.4, 26.8, and 53.6 mL/kg, respectively), and low-, medium-, high-, and very-high-concentration Lonicera japonica groups (6.7 mL/kg administered, containing 8, 40, 80, and 160 mg/mL Lonicera japonica extract, respectively). A rat model of acetylphenylhydrazine-induced G6PD deficiency was established in all groups except the normal control group, as confirmed by the morphological changes in erythrocytes observed using Wright's stain. After treatment, routine blood and biochemical tests were conducted to measure hemolytic indices, as well as changes in total and indirect bilirubin levels. Results Rats with G6PD deficiency demonstrated irregular erythrocytes with a lighter-staining center. In the positive control group, the red blood cell count decreased, while the free hemoglobin count and the reticulocyte percentage increased, as compared with before treatment (P < 0.05); in all the Yinzhihuang oral liquid groups and Lonicera japonica extract groups, all the above indices except reticulocyte percentage returned to the levels before treatment (P < 0.05). Compared with the positive control group, all the Yinzhihuang oral liquid groups had significantly reduced total and indirect bilirubin levels (P < 0.05), and all the Lonicera japonica group had significantly reduced indirect bilirubin levels (P < 0.05). However, the total bilirubin level was significantly higher in the Lonicera japonica groups than in the Yinzhihuang oral liquid groups (P < 0.05). The low-dose Yinzhihuang oral liquid group demonstrated a significantly greater decrease in total bilirubin level than the medium-and high-dose Yinzhihuang oral liquid group (P < 0.05). Conclusions Administration of high-dose Yinzhihuang oral liquid and different concentrations of Lonicera Japonica extract do not cause hemolysis in rats with G6PD deficiency. Yinzhihuang oral liquid is more effective in treating hyperbilirubinemia than Lonicera Japonica extract. However, the efficacy of Yinzhihuang oral liquid may not be dose-dependent.