含自然铜中药复方对SD大鼠的毒性病理学研究OA

Objective To investigate the long-term safety of YKY-018,a traditional Chinese medicine(TCM)compound containing pyritum,as well as the toxicopathological changes of copper in vital organs induced by this compound.Methods Sprague-Dawley(SD)rats were randomly divided into the vehicle control group and the low-,medium-,and high-dose YKY-018 groups(0.25,0.5 and 1 g·kg-1,respectively).The rats were administered the drug via oral gavage once daily for 13 consecutive weeks,followed by a 4-week recovery period after drug with drawal.Pathological evaluations were conducted by means of macroscopic morphological observation,organ weight measurement,organ-brain ratio calculation,hematoxylin-eosin(HE)staining,and specific staining for copper(rubeanic acid method).Results Macroscopic morphological observation showed that the high-dose group presented an enlarged kidney volume,along with significant increases in kidney weight and kidney-brain ratio.In male rats of the high-dose group,the liver weight and liver-brain ratio also increased significantly.HE staining revealed slight renal tubular hypertrophy in the low-dose group,and slight to mild renal tubular hypertrophy in the medium-and high-dose groups,while no abnormalities were detected in other tissues and organs.Rubeanic acid staining demonstrated the presence of copper in the renal tubular epithelial cells of the high-dose group.After the 4-week recovery period,all the aforementioned renal lesions returned to normal.Conclusion Following 13 weeks of repeated oral gavage administration of YKY-018 to rats at doses of 0.25,0.5,and 1 g·kg-1,dose-related minimal to slight hypertrophy of the renal tubular epithelial cells was observed.These pathological changes were reversible to normal levels after a 4-week recovery period.