DIDP通过线粒体-Caspase途径诱导昆明小鼠肝脏损伤的研究

为探究DIDP（Di-iso-decyl phthalate，邻苯二甲酸二异癸酯）对肝脏的影响及其可能的分子机制，以昆明小鼠为研究对象，选用Res（resveratrol，白藜芦醇）为抗氧化剂，分别设置对照组，0.15、1.5、15、150 mg/（kg·d）DIDP组，Res组，150 mg/（kg·d）DIDP+Res组，灌胃染毒9 d后，对小鼠肝脏切片进行HE染色观察，并检测ROS（reactive oxygen，活性氧）、GSH（glutathione，谷胱甘肽）、MDA（malondialdehyde，丙二醛）、Cyt-C（cytochromec，细胞色素C）、Caspase-3和血清中的ALT（alanine aminotransferase，丙氨酸氨基转移酶）含量.结果表明:与对照组相比，15、150 mg/（kg·d）DIDP组小鼠血清中ALT含量极显著上升（P < 0.01）；HE染色结果显示，15、150 mg/（kg·d）DIDP组小鼠出现肝细胞水肿、肝索紊乱、肝窦以及肝中央静脉扩张等现象；15、150 mg/（kg·d）DIDP组小鼠肝脏ROS含量显著上升（P < 0.05），GSH含量显著下降（P < 0.05），150 mg/（kg·d）DIDP组小鼠肝脏MDA含量极显著上升（P < 0.01）；1.5、15、150 mg/（kg·d）DIDP组小鼠肝脏中c（Cyt-C）极显著上升（P < 0.01）；15、150 mg/（kg·d）DIDP组小鼠肝脏中Caspase-3表达量极显著上升（P < 0.01）.DIDP染毒剂量的增加对肝脏的各种损伤程度呈上升趋势，Res可减轻上述DIDP对肝脏造成的各种损伤.研究显示，15、150 mg/（kg·d）DIDP可诱导肝脏组织氧化应激水平上升，进而造成线粒体损伤，导致细胞凋亡，造成肝功能受损，因此，线粒体-Caspase途径可能是DIDP诱导肝脏损伤的潜在机制之一. 

DIDP-Induced Liver Damage in Kunming Mice via Mitochondrial-Caspase Pathway

To elucidate the effect of Di-iso-decyl phthalate (DIDP) on mouse liver as well as the possible molecular mechanism, Kunming mice were used for the study and resveratrol (Res) was applied as an anti-oxidant to the mice, including the saline group, 0.15, 1.5, 15, 150 mg/(kg·d) DIDP groups, 20 mg/(kg·d) Res group and 150 mg/(kg·d) DIDP+20 mg/(kg·d) Res group. Mice were orally administrated with DIDP and/or Res for 9 consecutive days followed by execution for examination by HE staining and measurement of the content of ROS, GSH, MDA, Cyt-C, Caspase-3 and ALT. The results showed that compared with the saline group, the ALT content in serum in the 15 and 150 mg/(kg·d) DIDP group dramatically increased (P<0.01); the HE staining of liver revealed that hepatocyte edema, hepatic cord disorder, liver sinus and central venous dilatation appeared in the 15 and 150 mg/(kg·d) DIDP groups; both ROS (P<0.05) and MDA (P<0.01) content increased significantly in the 150 mg/(kg·d) DIDP group, while the GSH (P<0.01) content decreased; the Cyt-C (P<0.01) content increased dramatically in the 1.5, 15 and 150 mg/(kg·d) DIDP groups; the expression of Caspase-3 (P<0.01) in liver in the 15 and 150 mg/(kg·d) DIDP groups increased dramatically. Generally, the degree of various damages to liver rose with the increase of DIDP concentration, while Res could alleviate some of these effects caused by DIDP. This study demonstrated that 15 and 150 mg/(kg·d) DIDP could induce oxidative stress and mitochondrial impairment in liver, subsequently leading to cell apoptosis, so that damage to the liver occurred. Therefore, the mitochondrial-caspase pathway is probably responsible for the mechanism underlying the liver damage caused by DIDP.