Effect of status epilepticus on expression of brain UDP-glucuronosyltransferase 1a in rats
Effect of status epilepticus on expression of brain UDP-glucuronosyltransferase 1a in rats
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DOI：
10.1002/bdd.2114
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发表时间：
2018-02-01
影响因子：
2.1
通讯作者：
Katoh, Miki
中科院分区：
文献类型：
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作者：
Asai, Yuki;Tanaka, Hatsuna;Katoh, Miki
癫痫持续状态（SE）涉及严重的癫痫发作，导致大脑中的氧化应激。已知氧化应激影响尿苷5 '-二磷酸-葡萄糖醛酸基转移酶（UGT）1A的表达。本研究旨在阐明SE对大鼠脑内Ugt 1a 1、Ugt 1a 6和Ugt 1a 7表达的影响。用海人酸建立SE动物模型。Sprague-Dawley大鼠腹腔注射10 mg/kg红藻氨酸。在皮质和海马中，SE增加了Ugt 1a 1和Ugt 1a 7 mRNA水平（Ugt 1a 1：分别为4.0和5.3倍; Ugt 1a 7：分别为2.8和2.5倍）。此外，血红素氧合酶-1 mRNA的诱导程度，氧化应激标志物，在这些区域中是高的，这表明氧化应激可能参与Ugt 1a 1和Ugt 1a 7诱导。在SE和无反应（非癫痫发作反应）大鼠中，Ugt 1a 6在皮质中升高1.8倍，这意味着Ugt 1a 6诱导可能独立于SE。单次腹腔注射25 mg/kg地西泮（DZP）治疗SE可减弱皮层中血红素氧合酶-1的诱导，而海马中Ugt 1a 1减少，但皮层中不减少，这表明DZP治疗可能存在Ugt 1a 1减少的替代机制。DZP连续给药14天可抑制Ugt 1a 1在皮质中的诱导，但对Ugt 1a 7的诱导没有影响。本研究表明，SE改变了脑Ugt 1a 1和Ugt 1a 7的表达，从而改变了脑中的葡萄糖醛酸化。
Status epilepticus (SE) involves severe epileptic seizures that cause oxidative stress in the brain. Oxidative stress is known to influence uridine 5'-diposphate-glucuronosyltransferase (UGT) 1A expression. The present study aimed at elucidating the effect of SE on Ugt1a1, Ugt1a6 and Ugt1a7 expression in the rat brain. Kainic acid was used to create an animal model of SE. Sprague-Dawley rats were treated intraperitoneally with 10mg/kg kainic acid. Ugt1a1 and Ugt1a7 mRNA levels were increased by SE in the cortex and hippocampus (Ugt1a1: 4.0- and 5.3-fold, respectively; Ugt1a7: 2.8- and 2.5-fold, respectively). Moreover, the induction degree of heme oxygenase-1 mRNA, an oxidative stress marker, was high in these regions, suggesting that oxidative stress could be involved in Ugt1a1 and Ugt1a7 induction. Ugt1a6 was elevated by 1.8-fold in the cortex in both SE and non-response (non-epileptic seizure response) rats, implying that Ugt1a6 induction may be independent from SE. An intraperitoneal single administration of 25mg/kg diazepam (DZP) for the treatment of SE could attenuate heme oxygenase-1 induction in the cortex, whereas Ugt1a1 was decreased in the hippocampus, but not in the cortex, suggesting that there likely exists an alternative mechanism for Ugt1a1 reduction by DZP treatment. Continuous 14-day administration of DZP inhibited Ugt1a1 induction in the cortex, but did not have an effect on Ugt1a7 induction. This study indicated that SE altered the expression of brain Ugt1a1 and Ugt1a7, which could alter glucuronidation in the brain.