Hippocampal neuronal cyclooxygenase-2 downstream signaling imbalance in a rat model of chronic aluminium gluconate administration.
Hippocampal neuronal cyclooxygenase-2 downstream signaling imbalance in a rat model of chronic aluminium gluconate administration.
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DOI：
10.1186/s12993-015-0054-z
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发表时间：
2015-02-18
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Wang H;Ye M;Yu L;Wang J;Guo Y;Lei W;Yang J
包括神经退行性疾病在内的急性和慢性脑损伤是一组以认知功能障碍和进行性神经元丢失为特征的神经炎症相关疾病。脑损伤的病理生理过程涉及环氧合酶（考克斯）-2的过度表达。由于考克斯-2抑制剂对慢性脑损伤的治疗作用有限，且具有较迟的不良反应，因此考克斯下游信号通路已成为神经学研究的热点。为探讨铝的神经毒性机制及COX 2下游信号通路在慢性脑损伤中的作用，本研究采用葡萄糖酸铝（Al 2 O3）慢性染毒大鼠模型，观察海马前列腺素（PG）含量、PG氧化酶和PG受体表达的变化。用葡萄糖酸铝（Al 3+）200 mg/kg·d灌胃，每周5 d，共20周，建立大鼠慢性脑损伤模型。采用ELISA法、RT-PCR法和Western blotting法分别检测大鼠胃黏膜PG含量、PG酶和PG受体的表达。葡萄糖酸铝长期给药可导致大鼠海马神经元损伤和学习记忆障碍。葡萄糖酸铝给药还导致大鼠海马中PGE 2、PGD 2、TXA 2、PGI 2和PGF 2 α水平升高。海马组织DP 1、EP 2、IP、mPGES-1、EP 4、PGIS和TXAS mRNA表达及DP 1、EP 2和IP蛋白表达均显著增加，EP 3、FP mRNA和蛋白表达及TP mRNA表达均显著降低。慢性铝负荷大鼠海马PGS/PGs/PG受体信号通路紊乱，可能参与铝的神经毒性机制。
Acute and chronic brain damages including neurodegenerative diseases are a group of neuroinflammation-associated diseases characterized by cognitive function defect and progressive neuron loss. The pathophysiological procession of brain damages involves the overexpression of cyclooxygenase (COX)-2. Owing to the limited benefit to chronic brain damage and the late adverse effect of COX-2 inhibitors, the COX downstream signaling pathway has become a focus in neurological research. In order to explore the mechanism of aluminum neurotoxicity and the importance of COX2 downstream signaling pathways to chronic brain damage, the present study was designed to simultaneously observe the prostaglandin (PG) contents, and the expressions of PG synthases and PG receptors of hippocampus in a rat model induced by chronic administration of aluminium gluconate. A rat model of chronic brain damage was established by chronic intragastric administration of aluminium gluconate (Al3+ 200 mg/kg per day, 5d a week for 20 weeks). PG contents, the expressions of PG synthases, and the expressions of PG receptors in rats were measured by ELISA, RT-PCR and Western blotting, respectively. Chronic aluminium gluconate administration resulted in hippocampal neuron injury and learning and memory disorders in rats. Aluminium gluconate administration also resulted in increased levels of PGE2, PGD2, TXA2, PGI2, and PGF2α in rat hippocampus. The DP1, EP2, IP, mPGES-1, EP4, PGIS and TXAS mRNA expressions, and the DP1, EP2 and IP protein expressions significantly increased in the Al-treated hippocampus, while the EP3 and FP mRNA and protein expressions and the TP mRNA expression decreased. The PGS/PGs/PG receptors signaling pathway in chronic aluminium gluconate-overloaded rat hippocampus is disturbed, which may be involved in the mechanism of aluminium neurotoxicity.
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发表时间：
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期刊：
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影响因子：
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