大剂量何首乌醇提物致大鼠多脏器损伤研究

High dosage administration of Polygonum multiflorum alcohol extract caused the multi-organ injury in rats

目的观察大剂量何首乌对大鼠主要脏器的损伤作用,暴露其可能的毒性作用。方法采用亚急性毒性试验,初步比较生何首乌和制何首乌不同提取物(20g生药/kg)灌胃28天的毒性,观察肝脏病变频数;进一步对毒性较大的生何首乌和制何首乌醇提物进行研究,以40g生药/kg连续灌胃28天,观察大鼠体重增长情况、脏器指数变化、肝肾功能生化指标、组织病变结果。结果初步发现生何首乌和制何首乌醇提物毒性均大于各自的水提物和药材全粉,肉眼观察发现服药大鼠主要脏器中,肝脏发生显著病变的频数最高。何首乌醇提物毒性结果发现,与未给药动物比较,生何首乌组和制何首乌组大鼠体重增长显著受抑,生首乌组主要脏器指数显著升高;组织病理检查显示生何首乌组和制何首乌组肝、肾和肺脏均发生显著损伤;肝功能生化指标动态监测显示:生何首乌组谷丙转氨酶和谷草转氨酶仅在给药第3天时出现一过性显著升高,在此后第7、14、21和28天均无显著改变,而CCl4阳性对照组在实验第1周ALT和AST即出现显著升高。结论初步实验提示何首乌的肝毒性物质可能集中在醇提物,其毒性器官主要集中在肝脏。进一步实验提示生何首乌毒性大于制何首乌,何首乌对肝、肾和肺均有损伤,其中对肺脏的损伤作用是首次报道;肝功能生化指标谷丙转氨酶和谷草转氨酶对何首乌肝损伤不敏感,提示何首乌肝损伤的机制可能与CCl4主要基于细胞膜脂质过氧化的肝损伤机制不同。

Objective It is observed that the injury of mainly organs in rats caused by high dosage administration of Polygonum multiflorum （PM） and exposed their toxicity. Method Adopting the suba- cute toxicity test to study the different extracts of the crude and prepared PM repeated intragastric adminis- tration for 28 days at a dosage of 20 g/kg to observe the liver lesions frequency. Further-depth study of the toxicity of alcohol extract of PM was done and the weight gain, organ index, biochemical indicators reflect liver and kidney function and histopathology examination results were observed. Results It is showed that alcohol extract has more liver damage effect and toxic components than water extract and powder. Macro- scopic observation found that the liver produces significant lesions of the highest frequency in major organs.Further-depth study of the toxicity of alcohol extract of PM showed that the weight gain and organ index（ ex- cept prepared PM） were abnormal and there were toxic effects to liver, kidney and lung in rat after repeated intragastric administration of PM and its processed materials for 28 days at a dosage of 40 g/kg. Dynamic monitoring results indicate that ALT and AST had significant changes only on the third day while had no significant change at the first week, the second week, the third week and the fourth week thereafter. How- ever, ALT and AST increased significantly after the administration of CC14 （ positive control） one week lat- er. Conclusion The liver toxicity caused by PM may ascribe to the alcohol extract and toxic organs mainly concentrated in the liver. Further studies suggesting that the crude has greater toxicity than prepared and PM caused damage effect on liver, kidney and lung, especially the lung injury induced by PM is the first reported. Particularly worth mentioning that the alanine aminotransferase（ALT） and aspartate aminotrans- ferase （AST） which were the biochemical indicators reflect liver function were not sensitive to the liver tox- icity caused by PM. It is suggested that the mechanism of liver injury induced by PM may be different from CCI4 which is based on lipid oxidation of cell membrane.