■先前的研究表明,海藻酸(KA)引起的癫痫发作后,大鼠海马中的基因表达可以受到调节。这项研究的目的是研究KA给药对大鼠海马组织中负责药物代谢的酶的基因表达水平的潜在调节影响。
■大鼠接受剂量为10mg/kg的KA和盐水的腹膜内注射。在给予KA后,在实验动物中观察到行为变化。接受治疗四小时后,所有的老鼠都被斩首,大脑被切除了.海马组织用于总RNA分离,并通过逆转录聚合酶链反应(PCR)进行cDNA合成。负责药物代谢的酶的基因表达水平通过使用RT2ProfilerPCR阵列大鼠药物代谢PCR阵列系统的定量PCR来测定,所述系统包含总共84个基因的相关引物。使用比较Ct(2-ΔΔΔ(Δδ)Ct)方法定量药物代谢酶的基因表达水平。采用Studentt检验进行数据分析。
■我们的结果表明,KA处理引起了金属硫蛋白3,葡萄糖磷酸异构酶的基因表达水平的显著变化,三磷酸腺苷结合盒蛋白C1,细胞色素P450酶(Cyp2c6v1,Cyp3a23/3a1,Cyp2c7),谷胱甘肽过氧化物酶1,4和5,谷氨酸脱羧酶1和2,对氧磷酶2,碳水化合物磺基转移酶1,谷胱甘肽S-转移酶(Gsta3,Gstm1,Gstm4),微粒体谷胱甘肽S-转移酶3,羧酸酯酶2C,脂肪酸酰胺水解酶,丙酮酸激酶-肌肉,花生四烯酸5-脂氧合酶,载脂蛋白E,细胞色素b5还原酶5,黄嘌呤脱氢酶,N-乙酰转移酶1,葡萄糖激酶调节因子,己糖激酶2,富含肉豆蔻酰化丙氨酸的蛋白激酶C底物,与对照组相比,海马中的锡素(p<0.05)。
■作为结论,可以说,KA引发的癫痫发作活动有可能改变大鼠海马中负责药物代谢的酶的基因表达水平。
UNASSIGNED: Previous studies have shown that gene expressions can be regulated in the hippocampus of rats after seizures induced by kainic acid (KA). The aim of this study was to examine the potential regulatory impact of KA administration on gene expression levels of enzymes responsible for drug metabolism in rat hippocampal tissue.
UNASSIGNED: Rats received intraperitoneal injections of KA and saline at a dose of 10 mg/kg. Behavioral changes were observed in experimental animals following the administration of KA. Four hours after receiving treatments, all rats were decapitated, and the brains were removed. Hippocampal tissues were used for total RNA isolation, and cDNA synthesis was performed by reverse transcription polymerase chain reaction (PCR). Gene expression levels of enzymes responsible for drug metabolism were determined by quantitative PCR using the RT2 Profiler PCR Array Rat Drug Metabolism PCR array system containing the relevant primers for a total of 84 genes. The gene expression levels of drug-metabolizing enzymes were quantified using the comparative Ct (2-ΔΔ(delta delta)Ct) method. The Student\'s t-test was used for data analysis.
UNASSIGNED: Our results indicate that KA treatment caused significant changes in the gene expression levels of metallothionein 3, glucose phosphate isomerase, adenosine triphosphate-binding cassette protein C1, cytochrome P450 enzymes (Cyp2c6v1, Cyp3a23/3a1, Cyp2c7), glutathione peroxidase 1, 4, and 5, glutamic acid decarboxylase 1 and 2, paraoxonase 2, carbohydrate sulfotransferase 1, glutathione S-transferases (Gsta3, Gstm1, Gstm4), microsomal glutathione S-transferase 3, carboxylesterase 2C, fatty acid amide hydrolase, pyruvate kinase-muscle, arachidonate 5-lipoxygenase, apolipoprotein E, cytochrome b5 reductase 5, xanthine dehydrogenase, N-acetyltransferase 1, glucokinase regulator, hexokinase 2, myristoylated alanine rich protein kinase C substrate, and stannin in the hippocampus compared with the control (p < 0.05).
UNASSIGNED: As a conclusion, it can be said that the seizure activity triggered by KA has the potential to change the gene expression levels of the enzymes responsible for drug metabolism in the hippocampus of rats.