氨基脲诱导的SD大鼠氧化应激与肝脏代谢损伤研究

Study on semicarbazide-induced oxidative stress and hepatic metabolic damage in SD rats

中文关键词:  氨基脲  氧化应激  肝脏代谢酶  毒性效应

英文关键词:semicarbazide  oxidative stress  hepatic metabolizing enzymes  toxic effects

中文摘要:

      目的 研究氨基脲(semicarbazide, SEM)诱导的SD雄性大鼠氧化应激与肝脏代谢损伤。方法 随机将44只SD雄性大鼠均分4组: 对照组(C组)与SEM低、中、高剂量组(L组、M组、H组), SEM剂量分别为0.0、7.5、15.0、30.0 mg/(kg·bw), 连续灌胃28 d。利用酶联免疫法(enzyme-linked immuno sorbent assay, ELISA)测定大鼠血清SEM含量、血清与肝脏活性氧(reactive oxygen species, ROS)与8-异前列腺素F2α (8-isoprostaglandin F2α, 8-iso-PGF2α)含量、肝脏代谢酶细胞色素P450 (cytochrome P450, CYP450)、鸟苷二磷酸葡萄糖醛酸转移酶(uridine diphospho-glucuronosyl transferases, UGT)、谷胱甘肽硫转移酶(glutathione S-transferase, GST)与谷胱甘肽硫转移酶pi (glutathione S-transferase pi, GSTpi)指标以及大鼠尿液SEM含量。结果 对比C组, 各组血清SEM含量极显著升高(P<0.01), M组、H组血清ROS与H组肝匀浆8-iso-PGF2α含量极显著上升(P<0.01)。L组(P<0.05)、M组、H组(P<0.01)肝脏CYP450活力均显著下降。M、H组UGT活力与GSTpi含量显著降低(P<0.05), GST活力无显著性。SEM尿液排泄量随时间波动, 第10 d达到排泄峰值。结论 SEM短期重复染毒使其在大鼠体内蓄积, 影响机体氧化应激与肝脏代谢酶活性, 氧化应激可能对不同代谢酶产生不同抑制作用。

英文摘要:

      Objective To investigate the oxidative stress and liver metabolic damage in SD rats under semicarbazide (SEM) induction. Methods 44 SD male rats were randomly divided into 4 groups: Control (C) group and SEM low (L), medium (M) and high (H) dose groups with SEM doses of 0.0, 7.5, 15.0 and 30.0 mg/(kg·bw), respectively, then intragastrically administrated for 28 d. Enzyme-linked immuno sorbent assay method was used to measure the content of serum SEM, the content of reactive oxygen species (ROS) and 8-isoprostaglandin F2α (8-iso-PGF2α) in rat serum and liver respectively, liver metabolic enzymes index such as cytochrome P450 (CYP450), uridine diphospho-glucuronosyl transferases (UGT), glutathione S-transferase (GST) and glutathione S-transferase pi (GSTpi), and the content of urinary SEM. Results Compared with group C, serum SEM content was highly significantly increased in all groups (P<0.01), and there was an increasing statistical significant trend in serum ROS levels in groups M and H as well as liver homogenate 8-iso-PGF2α levels in group H (P<0.01). Liver CYP450 activity decreased significantly in groups L (P<0.05) and groups M and H (P<0.01). In addition, the activity of UGT and GSTpi content dropped significantly in M and H groups (P<0.05), and the activity of GST showed no significant change. SEM urinary excretion fluctuated with time, and reached the peak on the 10th day. Conclusion Short-term repeated exposure to SEM causes its accumulation in rats and affected oxidative stress and hepatic metabolic enzyme activity in the body. In addition, oxidative stress might have different inhibitory effects on different metabolic enzymes.