Z24对大鼠肝脏抗氧化体系的影响  

Effects of Z24 on rat liver antioxidation system

作　　者：王莹[1,2] 王全军[1] 董延生[1] 袁本利[1] 吴纯启[1] 廖明阳[1] 

机构地区：[1]军事医学科学院毒物药物研究所,国家北京药物安全评价研究中心 [2]辽宁医学院药物研究所

出　　处：《毒理学杂志》2008年第1期17-19,共3页Journal of Toxicology

摘　　要：目的研究Z24对大鼠肝脏抗氧化体系的影响。方法雌性Wistar大鼠,灌胃给予Z24(0、50、100、200 mg/kg),1次/d,连续5 d,以生理盐水作对照。给药结束后次日,检测血浆生化指标,肝匀浆丙二醛(MDA)、还原型谷胱甘肽(GSH)含量和铜锌-超氧化物歧化酶(CuZn-SOD)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽-S-转移酶(GST)活力,并做肝组织病理学检测。结果100、200 mg/kg组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TB1)升高(P<0.05),200 mg/kg组总胆汁酸(TBA)降低(P<0.05),光学显微镜下见各给药组均出现肝细胞空泡变性和纤维组织增生,电子显微镜下见200 mg/kg组有线粒体嵴断裂等改变,表明该剂量下Z24已引起了肝损伤。50 mg/kg组CuZn-SOD活力代偿性升高,100、200 mg/kg组GSH-Px活力降低(P<0.05),各给药组GST活力均升高,未见MDA含量升高和GSH含量降低,表明该剂量下Z24未引起肝氧化和抗氧化能力失平衡。结论Z24对GSH-Px有抑制作用,但氧化应激效应并不是Z24肝毒性作用的主要机制。Objective To study effects of Z24 on rat liver antioxidation system. Methods Female Wistar rats were intragastric administrated 50, 100 and 200 mg/kg Z24 for 5 days, respectively, and the control group were treated with purified water. On the sixth day, rats sacrificed, then malondialdehyde（ MDA）, reduced glutathione（ GSH）, Copper and zinc superoxide dismutase（ CuZn-SOD）, and glutathione peroxidase（GSH-Px） glutathione S-transferase（GST） of liver homogenate were detected, and some blood plasma biochemical indicators, hepatic tissue pathology were detected. Results The levels of alanine aminotransferase （ALT）, asparate aminotransferase （AST）, alkaline phosphatase（ALP） and total bilirubin（TBI） in 100, 200 mg/kg group were higher than those of control group （P 〈 0.05）and total bile acid（TBA） level in 200 mg/kg group was lower than the control（ P 〈 0.05）. Hepatocyte vacuolar degeneration and fibroplasias were observed in tissue sections of Z24 treated groups through optical microscope, and pathological changes such as mitochondrial cristae breakage were seen in sections of 200 mg/kg group through electron microscope. These results indicated that Z24 could damageliver at these doses. In liver homogenate, contrasted with the control, activity of CuZn-SOD in 50 mg/kg group was compensated increased, activity of GSH-Px in 100 and 200 mg/kg groups was decreased, and activity of GST in all three Z24 groups was increased, but no higher MDA level and lower GSH level were seen, which indicated rat liver oxidation and antioxidation system still being balanced at toxiferous dose.Conclusion Z24 can suppress GSH-Px activity, but oxidative stress does not play the major role in Z24 induced hepatotoxic effect.

关 键 词：Z24 肝脏 抗氧化物 

分 类 号：R99[医药卫生—毒理学]