大鼠何首乌水提物短期灌胃的肝毒性研究  

Hepatotoxicity of Short Time Oral Administration of Aqueous Extract of Polygoni Multflori Radix in Rats

作　　者：全正扬 陈静[1] 李登科[1] 费占洋[1] 王子建[1] 周明[1] 李凯明[1] 孙震晓[1] 

机构地区：[1]北京中医药大学,北京100102

出　　处：《中国药物警戒》2017年第6期321-325,共5页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(81473418):肝细胞色素P450酶表达低下致何首乌特异质肝毒性机制研究;北京中医药大学校级课题东直门医院"111"协同创新院际合作项目(2016-DZM111-ZY008):何首乌相关临床肝毒性及其与人P450酶遗传多态性的关系;北京中医药大学2017在读研究生自主课题(2017-JYB-XS-145):基于肝药酶调控的何首乌及其主要成分的代谢特征研究

摘　　要：目的考察何首乌水提取物连续灌胃大鼠后短期内肝毒性相关血清生化指标等的变化情况。方法分别用低、高剂量(10、30 g·kg^(-1))何首乌水提取物灌胃雄性SD大鼠,灌胃期间每天观察大鼠一般状况并称重,每周计算一次食物利用率;在灌胃何首乌水提物1 d和连续灌胃14 d后,分别测定大鼠血清中主要肝功能相关指标ALT、AST、ALP、TBIL、DBIL、IBIL水平;并在连续灌胃14 d后,对动物实施安乐死,解剖后大体观察,并取肝脏称重计算肝脏系数、制备肝脏组织切片HE染色观察肝脏的病理学变化。结果灌胃何首乌水提物组大鼠出现怠动、便软、尿液颜色加深、毛色不华等现象;低、高剂量何首乌水提取物灌胃大鼠后每周的食物利用率、肝重及肝脏系数较空白对照组没有明显差异;灌胃何首乌水提物1 d和14 d后,各组大鼠血清中ALT、AST、ALP水平均无明显差异;灌胃何首乌水提物1 d后,低剂量何首乌组大鼠血清中TBIL水平较空白对照组升高(P<0.05),高剂量何首乌组大鼠血清中TBIL、IBIL水平均较空白对照组显著升高(均P<0.01);连续灌胃何首乌水提物14 d后,高剂量组大鼠血清中TBIL、DBIL、IBIL水平均较空白对照组显著升高(均P<0.01);肝脏病理切片结果显示:何首乌水提物灌胃14 d后,高剂量何首乌组大鼠肝脏有部分肝细胞发生空泡化、枯否细胞肥大增生,汇管区附近有成纤维细胞肥大增生现象。结论一定浓度何首乌水提物灌胃大鼠后,短时间即能引起大鼠胆红素水平显著升高,造成肝细胞损伤性肝损伤。Objective To investigate the sensitive after short-time continuous oral administration of hepatotoxicity related blood serum biochemical indicators in rats aqueous extract of Polygoni Multflori Radix （AEPMR）. Methods Male SD rats were orally administered with low and high dose （10,30 g·kg-1） of AEPMR once a day for 14 d. During the administration period, observed the rat general condition and weighed rats every day, and calculated food utilization rate weeHy. Detected the levels ofALT, AST, ALP, TBIL, DBIL, and IBIL in rats after 1 d and 14 d administration. 14 d AEPMR administration later, rats were euthanized and anatomized for general observation. The liver of rats was weighed to calculate liver coefficient and then made to slices stained with hematoxylin and eosin （HE staining） for histopathological analysis. Results Rats appeared tired, stool soft, urine color deepened and fur not bright after AEPMR administration. There was no significant difference among groups in liver coefficient, weekly food utilization and ALT, AST, ALP levels in serum after 1 d and 14 d administration. Compared with control group, TBIL of low-dose group （P〈0.05） and TBIL and DBIL of high-dose group （P〈0.01） were significantly increased after 1 d administration. TBIL, DBIL and IBIL of high-dose group were significantly increased after 14 d administration （P〈0.01）. Liver pathological analysis showed that in rats administered with high dose of AEPMR for 14 d, parts of the liver had observed vacuolization of hepatocytes and Kupffer cell hypertrophic hyperplasia, and fibroblasts hypertrophichyperplasiainportalareaOonclusionCertain dose of AEPMR could induce increase of blood serum bilirubin and liver injury of hepatocyte injury in rats after short-time oral administration.

关 键 词：何首乌水提取物 肝损伤 总胆红素 间接胆红素 直接胆红素 

分 类 号：R992[医药卫生—毒理学]