苦豆子抗内毒素效应的实验研究

Antiendotoxic Effects of Sophora alopecuroides L.

目的:研究苦豆子中提取的苦豆子总碱及氧化苦参碱、槐定碱、槐果碱对内毒素肺损伤小鼠模型的干预作用及其作用机制。方法:以清开灵注射液作为本研究的阳性对照药物。分别连续3天腹腔注射给予ICR小鼠各个生物碱及清开灵,均末次给药后1 h腹腔注射LPS(E.coil,055∶B5)9 mg/kg造成小鼠内毒素性肺损伤,观察小鼠一般状况、白细胞数量、肺W/D比值、肺组织病理形态学改变,以及免疫组织化学法检测肺组织CD14和清道夫受体(SR-A)的表达,放免法检测血清肿瘤坏死因子(TNF-α)和白细胞介素-6(IL-6)含量。结果:预防性给予内毒素肺损伤小鼠苦豆子总碱和三种苦豆子单体碱,均不同程度改善了模型鼠的一般状况,并可不同程度地升高外周血白细胞,降低肺脏W/D比值,减轻肺组织病理改变,降低模型鼠肺组织CD14表达,增加SR-A表达,降低血清中TNF-α和IL-6的水平。结论:苦豆子总碱和三种苦豆子单体碱可不同程度地减轻内毒素肺损伤小鼠的病理损害,它们的抗内毒素机制可能与调节LPS的识别受体,并进而影响下游炎症因子表达有关。

Objective： To investigate the effect and explore the mechanism of protective role exerted by Total Alkaloids of Sophora Alopecuroides and three kinds of pharmaeoalkaloids （Sophocarpine, Sophoridine, Oxymatrine） in mouse model with acute lung injury. Methods： Qingkailing Injection was used as positive control. The mouse model with lung injury induced endotoxin was established by peritoneal injection of LPS 1 h after the last administration. The ICR mice were pretreated with Total Alkaloids of Sophora Alopeeuroides 25 mg/kg, Sophoridine 5 mg/kg, Oxymatrine 50 mg/kg and Sophocarpine 25 mg/kg for 3 days respectively. The anti-endotoxin effect of Total Alkaloids of Sophora Alopecuroides and the three kinds of pharmacoalkoids in vivo was studied by the general symptoms, white blood cell count, lung wet/dry weight, pathological histologic changes of lung tissues. CD14 and SR-A of lung tissue and serum TNF-α and IL-6 were detected by immunohistoehemieal and radioimmunity method. Results： The general symptoms were improved, the number of white blood cells were increased, lung wet/dry weight was decreased and pathological changes of lung tissues were milder at different level. Meanwhile the expression of CD14 was decreased but the expression of SR-A increased in the lung tissue. Both the level of serum TNF-α and IL-6 were deerased. Conclusion： The damage of lung tissue in the mice with endotoxemia is inhibited by the Total Alkalids of Sophora Alopeeuroides and the three kinds of pharmaeoalkaloids at different level. The anti-endotoxin mechanism is associated with the regulating expression of LPS recognition receptor and down-regulating the expression of the down-stream inflammatory factors.