美洛昔康对Aβ诱导的阿尔茨海默病模型大鼠脑内环氧合酶-2的作用

Effect of Meloxicam on the Cyclooxygenase-2 Induced by Aβ in Alzheimer' s Disease Model Rats

目的研究美洛昔康对β-淀粉样蛋白(Aβ)诱导的阿尔茨海默病(AD)模型大鼠脑内环氧合酶-2(COX-2)的作用,并探讨其抑制炎症作用的机制。方法采用Aβ_(1-40)海马注射建立AD大鼠模型。术后第2天各组大鼠灌胃给药,连续30 d。美洛昔康小、中、大剂量分别为1、2、4 mg·kg^(-1)·d^(-1)。生理盐水对照组及模型对照组分别给予等容量生理盐水及0.5%羧甲基纤维素钠溶液。电迷宫刺激器检测大鼠学习记忆能力;尼氏染色观察大鼠海马形态结构变化;RT-PCR方法检测大鼠海马组织COX-2 mRNA的表达情况。结果美洛昔康能提高AD大鼠的学习记忆能力,改善AD大鼠脑组织的病理变化,抑制AD大鼠海马COX-2 mRNA的表达。结论美洛昔康可能通过抑制COX-2 mRNA的表达,减少前列腺素(PG)、活性氧(ROS)的生成,从而改善脑组织的病理变化,保护神经细胞,提高AD模型大鼠的学习记忆能力。

Objective To investigate the effect and mechanism of meloxicam on the cyclooxygenase- 2 （COX-2） induced by beta amyloid protein in Alzheimer＇ s disease （AD） model rats. Methods The rat model was established by the microinjection of Aβ1-40 into hippocampus. The drugs were given intragastrically daily for 30 days the day after operation. Different doses of the drug （ 1, 2 and 4 mg ·kg^ -1 ·d^ -1 ） were administered to the rats in the meloxicam groups. In the rats of the saline control group and AD model group the same volume of normal saline and 0.5 % sodium carboxymethyl cellulose were administered. The capacity for learning and memorizing was tested in rats with electrical maze. The change of structure in hippoeampus was observed by Nissle＇ s staining. The expression of COX-2 mRNA was tested by RTPCR. Results The capacity for learning and memorizing and the lesion of cerebral tissues in AD model was able to be enhanced by meloxicam. The expression of COX-2 mRNA was decreased by meloxicam. Conclusion Meloxicam may ameliorate the pathological change in AD model rat＇ s brain through inhibiting the expression of COX-2 mRNA, the generation of prostaglandin and the injury of reactive oxygen species.