含何首乌的中药滋肾育胎丸对犬的慢性肝脏毒性研究

Chronic hepatotoxicity evaluation of Chinese medicinal herb Zishen Yutai pill prepared from Polygoni Multiflori Radix preparata in dogs

研究含药典推荐剂量制何首乌的中药滋肾育胎丸对正常比格犬的慢性肝脏毒性。给药组犬分别灌胃给予低、中、高剂量组（1.5,3.0,6.0 g·kg^-1）的滋肾育胎丸,同时给予同体积的去离子水作为溶媒对照组,每天1次,共39周。给药期间每天观察动物的一般状况,并于给药前、给药13,26,39,43周采血,测定犬血清肝脏毒性相关的生物标志;于给药13,39,43周后分别解剖雌雄各2/7,3/7,2/7只动物,观察动物脏器病变、称量主要脏器质量并对肝脏进行病理检查。结果发现与溶媒对照组相比,给药3,6,9个月和恢复期1个月,各给药组比格犬AST,ALT等11项肝毒性传统生物标志均未见与受试物有关的变化;肝脏脏器指数和肝脏病理学检查均未见明显异常。因此,正常比格犬连续9个月灌胃给予滋肾育胎丸,剂量分别为1.5,3.0,6.0 g·kg^-1,未见明显慢性肝脏毒性。

To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill（ZYP） prepared from Polygonum multiflorum with the recommended dosage in normal Beagle dogs. Low,middle and high doses of ZYP（1. 5,3. 0,6. 0 g·kg^-1; i. e. 3 ×,6 ×and 12 × equivalent doses） were given orally to dogs for 39 consecutive weeks. At the same time,the same volume of deionized water was used as the solvent control group,one time a day. The general condition of the animals was observed every day during the period of administration,and the blood was collected before and 13,26,39,43 weeks after administration to detect the biomarkers related to the hepatotoxicity of the dog serum. 2/7,3/7 and 2/7 animals were dissected after 13,39,and 43 weeks of administration to observe the pathological changes of the animal organs,weigh the mass of main organs and conduct pathological examination of the liver. As compared to the solvent control group,11 liver hepatotoxicity traditional biomarkers such as ALT,AST were found no ZYP-related changes at month 3,6,9 of the administration and month 1 in recovery period; There was no significant difference in liver viscera index and liver pathology. Therefore,no obvious hepatotoxicity was shown by ZYP administered up to 6. 0 g·kg^-1 for 9 months in normal dogs at doses of 1. 5,3. 0,and 6. 0 g·kg^-1.