Curcumin Induces ABCA1 Expression and Apolipoprotein A-I-Mediated Cholesterol Transmembrane in the Chronic Cerebral Hypoperfusion Aging Rats
Curcumin Induces ABCA1 Expression and Apolipoprotein A-I-Mediated Cholesterol Transmembrane in the Chronic Cerebral Hypoperfusion Aging Rats
复制标题
姜黄素诱导慢性脑低灌注衰老大鼠 ABCA1 表达和载脂蛋白 A-I 介导的胆固醇跨膜
DOI：
10.1142/s0192415x13500699
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发表时间：
2013-01-01
影响因子：
5.7
通讯作者：
Li, Yu
中科院分区：
文献类型：
--
作者：
Tian, Mingyuan;Zhang, Xiong;Li, Yu
脑低灌流或衰老往往导致胆固醇和脂蛋白的紊乱，这是一种常见的病理状态，导致神经退行性疾病，如血管性痴呆(VaD)和阿尔茨海默病(AD)。肝X受体-β(LXR-β)/维甲酸X受体-α(RXR-α)/ABCA1通路在脂蛋白代谢中起着至关重要的作用。姜黄素是一种酚类化合物，应用广泛。已有报道称姜黄素可降低血清胆固醇水平，但其潜在机制尚不清楚。在本研究中，我们评估了姜黄素对脑内胆固醇水平、血管认知功能障碍的影响，并探讨了这些作用的机制是否通过激活LXR-β/RXR-α、ABCA1表达和apoA-I来实现。通过Morris水测试，我们发现姜黄素治疗可以减轻认知障碍。苏木精-伊红染色和尼氏染色发现，姜黄素能明显改善锥体神经元的异常改变。姜黄素作用后，LXR-β、RXR-α、ABCA1和apoA-I的mRNA和蛋白表达均呈剂量依赖性增加。有趣的是，姜黄素治疗组的血清高密度脂蛋白胆固醇和总胆固醇水平在统计学上都高于其他组。我们认为姜黄素具有激活LXR-β/RXR-α信号通路，从而调节ABCA1和apoA-I介导的胆固醇跨膜转运的能力，这是一种新的预防和治疗脑血管疾病的策略。
Cerebral hypoperfusion or aging often results in the disturbances of cholesterol and lipoprotein, which have been well depicted as a common pathological status contributing to neurodegenerative diseases such as vascular dementia (VaD) and Alzheimer's dementia (AD). The pathway of the liver X receptor-beta (LXR-beta)/retinoic X receptor-alpha (RXR-alpha)/ABCA1 plays a vital role in lipoprotein metabolism. Curcumin, a kind of phenolic compound, has been widely used. It has been reported that curcumin can reduce the levels of cholesterol in serum, but the underlying mechanisms are poorly understood. In this study, we evaluated the effects of curcumin on the cholesterol level in brain, vascular cognitive impairment and explored whether the mechanisms for those effects are through activating LXR-beta/RXR-alpha and ABCA1 expression and apoA-I. With a Morris water test, we found that curcumin treatment could attenuate cognitive impairment. With HE and Nissl staining, we found that curcumin could significantly ameliorate the abnormal changes of pyramidal neurons. Meanwhile, the expression of LXR-beta, RXR-alpha, ABCA1 and apoA-I mRNA and protein were increased in a dose-dependent manner after curcumin treatment. Interestingly, both serum HDL cholesterol and total cholesterol levels were statistically higher in the curcumin treatment group than those other groups. We conclude that curcumin has the ability to activate permissive LXR-beta/RXR-alpha signaling and thereby modulate ABCA1 and apoA-I-mediated cholesterol transmembrane transportation, which is a new preventive and therapeutic strategy for cerevascular diseases.