摘要
基于内毒素特异质肝损伤模型,考察何首乌对大鼠肝脏的损伤作用。将何首乌(Polygonum multiflorum Thunb.)50%乙醇提取物单独灌胃或联合无毒剂量的脂多糖(lipopolysaccharide,LPS,尾静脉注射2.8 mg·kg-1)给予SD大鼠,检测血清丙氨酸氨基转氨酶(ALT)、天冬氨酸氨基转氨酶(AST),HE染色观察肝脏病理学改变,对比考察何首乌单用或联合LPS的量-毒关系,探讨LPS对何首乌肝损伤的影响。结果表明,单次灌胃18.9、37.8、75.6 g·kg-1的何首乌对大鼠ALT、AST无显著影响(均P>0.05),肝脏切片未见明显病理学改变;单独尾静脉注射无毒剂量的LPS,对ALT、AST无显著影响(均P>0.05),肝脏切片可见汇管区炎症细胞增多,未见肝细胞有明显病理学改变;而相同剂量的何首乌联合LPS给药后,ALT、AST显著升高(均P<0.01),肝脏切片可见中央静脉扩张、内膜脱落,中央静脉周肝细胞肿胀、坏死,汇管区有大量炎症细胞浸润,中间区部分肝细胞肿胀、坏死。进一步降低何首乌给药剂量,1.08及2.16 g·kg-1(分别相当于生何首乌6 g/日,临床剂量的2倍、4倍等效剂量)联合LPS仍然显著升高大鼠ALT、AST(均P<0.05),而0.54 g·kg-1何首乌对ALT、AST无显著影响(均P>0.05)。研究表明,对于普通正常大鼠,单次灌胃给药超大剂量(75.6 g·kg-1)何首乌无明显肝损伤作用;而在LPS特异质肝损伤模型上,临床2倍等效剂量(1.08 g·kg-1)的何首乌即可造成实验大鼠肝功能损伤,该模型可用于何首乌特异质肝损伤评价。
The liver injury induced by Polygonum multiflorum Thunb. （PM） was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide （LPS） at a non-hepatotoxic dose.Sprague-Dawley （SD） rats were intragastrically administered with three doses （18.9, 37.8, 75.6 g crude drug per kg body weight） of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS （2.8 mg ＂kg^-1） via tail vein injection. The plasma alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or cotreatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS （2.8 mg ·kg^-1, iv） or different dosage （18.9, 37.8 and 75.6 g·kg^-1, ig） of PM, compared to normal control group （P 〉 0.05）; while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM （75.6 g.kg-~, ig） caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities （P 〈 0.05） were still observed in co-administration groups of LPS and PM （1.08 or 2.16 g.kg^-1）, but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM （0.54 g＇kg^-1） with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g.kg^-1 of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM （1.08 g .
出处
《药学学报》
CAS
CSCD
北大核心
2015年第1期28-33,共6页
Acta Pharmaceutica Sinica
基金
国家重大新药创制专项课题(2015ZX09501-004-001-008)
国家公益性行业专项课题(201507004-04)
国家自然科学基金资助项目(81373984
81403126)
关键词
何首乌
特异质肝损伤
内毒素
评价模型
量-毒关系
Polygonum multiflorum
idiosyncratic hepatotoxicity
endotoxin
animal model
dose-toxicity relationship
