目的 基于内毒素特异质模型, 比较何首乌炮制前后对大鼠肝脏损伤作用的差异。方法 采用无毒剂量的脂多糖(LPS, 尾iv 2.8 mg/kg)制备内毒素特异质模型大鼠, 模型大鼠和正常大鼠均ig给予生首乌和制首乌50%乙醇提取物(生首乌剂量分别为生药1.08和2.16 g/kg;制首乌剂量分别为生药1.08、2.16、4.32、8.64、17.28 g/kg), 各给药1次, 检测大鼠血浆中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平, HE染色观察肝脏病理学改变。结果 在正常SD大鼠上, 生首乌及制首乌单次给药8.64 g/kg以下, 未见有明显肝损伤作用;在内毒素特异质模型上, 生首乌1.08 g/kg剂量(相当于生首乌6 g/d临床剂量的2倍等效剂量)可造成实验大鼠肝功能损伤, 制首乌8.64 g/kg剂量(相当于制首乌12 g/d临床剂量的8倍等效剂量)对实验大鼠肝功能造成损伤。炮制后首乌中二苯乙烯苷的量下降明显。结论 在内毒素特异质模型上, 生首乌在接近临床等效剂量的情况下即可表现出肝损伤作用, 而制首乌表现出肝损伤的剂量扩大4倍, 提示炮制可降低何首乌的特异质肝毒性。

Objective To investigate the effects of crude and prepared Polygonum multiflorum (PM) to liver injury based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose, aiming to compare the difference between them. Methods The Sprague-Dawley (SD) rats were used by ig administration, respectively with 50% alcohol extracts from crude or prepared PM alone or co-treated noninjurious dose of bacterial lipopolysaccharide (LPS, 2.8 mg/kg) via tail vein injection. Blood was collected from the inferior vena cava into a sodium citrate-anticoagulant tube, and the liver was removed. The plasma samples separated from the collected blood were used for analysis on ALT and AST activities and the isolated livers were used for histopathological assessment. Results Both crude and prepared PM were nontoxic on normal SD rats under the dose of 17.28 g/kg, when co-treated with LPS, the liver injury was found at the dose of 1.08 g/kg of crude PM, however, 8.64 g/kg of prepared PM. Conclusion When processed, the maximum safe therapeutic dosage of PM would be enlarged from 1.08 g/kg of crude PM that is close to clinical dosage to 8.64 g/kg of prepared PM, which is four times larger than the crude one in LPS model. It shows that toxicity of PM could be reduced by processing.

国家自然科学基金资助项目(81373984);国家"重大新药创制"科技重大专项课题(2015ZX09501-004-001-008);国家公益性行业科研专项课题(201507004-04);北京市自然科学基金项目(7152142)