1,3-二苯-1,3-丙二酮对CdCl_2致小鼠急性肝肾损伤的保护作用  

Effect of 1,3-diphenyl-1,3-propanedione on acute hepatotoxicity and nephrotoxicity induced by CdCl_2 in mice

作　　者：杨东旭[1] 祝靓靓[1] 贾凤兰[1] 阮明[1] 张宝旭[1] 

机构地区：[1]北京大学公共卫生学院毒理学系,国家中医药管理局中药配伍减毒重点研究室,北京100191

出　　处：《中国新药杂志》2013年第14期1627-1631,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2009ZX09103-007)

摘　　要：目的:研究1,3-二苯-1,3-丙二酮(1,3-diphenyl-1,3-propanedione,DPPD)对CdCl2致雄性小鼠急性肝肾损伤的保护作用。方法:成年雄性小鼠分别经ig给予DPPD 200,400,800 mg.kg-1,连续给药4 d,然后经ip给予CdCl27.5 mg·kg-1,24 h后处死小鼠。测定血清中天冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)和乳酸脱氢酶(LDH)的水平;分别测定肝脏和肾脏组织中丙二醛(MDA)、还原性谷胱甘肽(GSH)、氧化性谷胱甘肽(GSSG)的含量,并计算GSH/GSSG比值。留取肝脏和肾脏组织,常规石蜡包埋切片,HE染色,光学显微镜下观察肝脏和肾脏组织的病理变化。结果:DPPD明显的降低血清AST,ALT和LDH的水平,并且呈剂量-反应关系;肝脏和肾脏的MDA含量以及GSH/GSSG比值显示DPPD可以明显改善CdCl2造成的脂质过氧化损伤和谷胱甘肽的消耗;肝脏和肾脏组织病理观察结果显示DPPD明显抑制CdCl2造成的损伤。结论:DPPD对CdCl2致小鼠急性肝肾损伤具有有效的保护作用。Objective： To determine the effect of 1,3-diphenyl-1,3-propanedione（DPPD） on acute nephrotoxicity and hepatotoxicity induced by CdCl2 in male mice.Methods： Adult ICR male mice were orally administered with DPPD at doses of 200,400,800 mg.kg-1 for 4 days.Then the mice were intraperitoneally injected with a single dose of CdCl2 7.5 mg.kg-1 and were killed 24 h after CdCl2 injection.The serum chemical parameters including asparate aminotransferase（AST）,alanine aminotransferase（ALT） and lactate dehydrogenase（LDH） were measured.Also malonaldehyde（MDA）,glutathione（GSH）,oxidized glutathione（GSSG） levels in the liver and kidney as well as glutathione（GSH） / oxidized glutathione（GSSG） ratios were detected.Histopathologic changes in the liver and kidney were examined.Results： DPPD significantly reduced serum AST,ALT and LDH levels in a dose-dependent manner.The results of MDA levels and GSH / GSSG ratios in liver and kidney showed that DPPD reduced CdCl2-induced hepatic lipid peroxidation,and ameliorated glutathione depletion.The histopathologic results showed that DPPD restrained liver and kidney damage induced by CdCl2.Conclusion： DPPD can effectively protect male mice from acute hepatotoxicity and nephrotoxicity induced by CdCl2.

关 键 词：1 3-二苯-1 3-丙二酮 镉 肝毒性 肾毒性 小鼠 

分 类 号：R961[医药卫生—药理学]