原卟啉钠对四氯化碳致小鼠急性肝损伤的保护作用及其机制

Study on Protective Effect and Related Mechanism of Protoporphyrin Disodium on Acute Hepatic Injury Induced by Carbon Tetrachloride in Mice

目的:研究原卟啉钠(NAPP)对四氯化碳(CCl4)所致小鼠急性肝损伤的保护作用及其机制。方法:60只ICR小鼠随机分为正常对照组、模型组、联苯双酯组、NAPP低、中、高剂量组,每组10只。各治疗组每天ig给予联苯双酯(0.2 g.kg-1)或不同剂量(0.03,0.06,0.12 g.kg-1)的NAPP,连续10 d后,1次性ip CCl4 0.06 g.kg-1建立急性肝损伤模型。16 h后,摘眼球取血测定血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性;剖腹取肝,称质量,计算肝脏指数;制备肝组织匀浆测定过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量,并观察肝组织病理学变化。结果:与CCl4模型组比较,各治疗组小鼠肝脏指数、血清ALT和AST活性不同程度降低(P<0.05,P<0.01);肝组织匀浆中CAT,GSH-Px,SOD活力不同程度升高(P<0.05,P<0.01),MDA含量不同程度降低(P<0.05,P<0.01);病理切片表明NAPP各治疗组小鼠肝损伤不同程度减轻,其中高剂量组肝损伤程度最轻。结论:NAPP对CCl4所致小鼠急性肝损伤具有明显的保护作用,其机制可能与NAPP的抗脂质过氧化作用和阻止抗氧化酶活性降低有关。

Objective：To study the hepato-protective effect and the related mechanisms of protoporphyrin disodium（NAPP） on carbon tetrachloride（CCl4） induced acute hepatic injury in mice.Method：Sixty ICR mice were randomly divided into normal control group,model group,bifendate pills group,NAPP low dose group,NAPP medium dose group and NAPP high dose group,with 10 animals in each group.Bifendate pills（0.2 g.kg-1） or dif-ferent dosages（0.03,0.06,0.12 g.kg-1）of NAPP were given for each treatment by intragastric administration con-tinuously for 10 days and then a single dose of CCl4 at 0.06 g.kg-1 CCl4was given by intraperitoneal injection to es-tablish acute hepatic injury model.Sixteen hours later,blood was collected to detect the activities of alanine amin-otransferase（ALT）and aspartate aminotransferase（AST）in serum·Liver was taken out by laparotomy and weighed to calculate liver index,and liver homogenate was prepared to determine the activities of catalase（CAT）,glutathione peroxidase（GSH-Px）and superoxide dismutase（SOD） and the content of malondialdehyde（MDA）.The observationof liver histopathological change was made for the mice.Result：Compared with CCl4model group,the liver indices and the activities of ALT and AST in serum of each treatment group were decreased significantly to various degrees（P 〈 0.05,P 〈 0.01）,the activities of CAT,GSH-Px and SOD in liver homogenate of each treatment group were in-creased dramatically at different extent（P 〈 0.05,P 〈 0.01）,and the content of MDA of each treatment group in liver homogenate was reduced remarkably at different degree（P 〈 0.05,P 〈 0.01）.The pathological sections showed that hepatic injury of each treatment group was relieved to different extent clearly,and the slightest group was NAPP high dose group.Conclusion：NAPP has a good protective effect on the acute hepatic injury in mice induced by CCl4,and the mechanism is probably related with the anti-lipid-peroxidation effect and the prevention of the decrease of liver anti-oxidative enzyme activities.