Pathological Department of Affiliated Hospital, Guiyang Medical College, China.
Acta Pharmacol Sin. 2011 Dec;32(12):1446-53. doi: 10.1038/aps.2011.115. Epub 2011 Oct 10.
To examine the protective effects of scutellarin (Scu) on rats with learning and memory deficit induced by β-amyloid peptide (Aβ).
Fifty male Wistar rats were randomly divided into 5 groups: control, sham operation, Aβ, Aβ+Scu, and Aβ+piracetam groups. Aβ(25-35) was injected into the lateral ventricle (10 μg each side). Scu (10 mg/2 mL) or piracetam (10 mg/2 mL was intragastrically administered per day for 20 consecutive days following Aβ treatment. Learning and memory was assessed with Morris water maze test. The protein and mRNA levels of nicotinic acetylcholine receptor (nAChR) α4, α7, and β2 subunits in the brain were examined using Western blotting and real-time PCR, respectively. The activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain and plasma were measured using Ellman's colorimetric method.
In Aβ group, the escape latency period and first platform cross was significantly increased, and the total number of platform crossings was significantly decreased, as compared with the control and the sham operation groups. Both Scu and piracetam treatment significantly reduced the escape latency period and time to cross platform, and increased the number of platform crosses, but there were no significant differences between Aβ+Scu and Aβ+piracetam groups. In Aβ group, the protein levels of nAChR α4 and α7 subunits in the cerebral cortex were significantly decreased by 42%-47% and 58%-61%, respectively, as compared to the control and the sham operation groups. Scu treatment caused upregulation of α4 and α7 subunit proteins by around 24% and 30%, respectively, as compared to Aβ group, but there were no significant differences between Aβ+Scu and Aβ+piracetam groups. The protein level of nAChR β2 subunit had no significant difference among different groups. The mRNA levels of nAChR α4, α7, and β2 subunits were not significantly changed. In Aβ group, the activities of AChE and BuChE in the brain were significantly increased, but were significantly decreased in the plasma, as compared to the control and the sham operation groups. Scu or piracetam treatment restored the activities in brain and plasma nearly to the levels in the control group.
The results suggest that Scu may rescue some of the deleterious effects of Aβ, possibly by stimulating nAChR protein translation and regulating cholinesterase activity.
观察野黄芩苷（Scu）对β-淀粉样肽（Aβ）诱导的学习记忆障碍大鼠的保护作用。
50 只雄性 Wistar 大鼠随机分为 5 组：对照组、假手术组、Aβ组、Aβ+Scu 组和 Aβ+吡拉西坦组。Aβ（25-35）侧脑室注射（每侧 10μg）。Aβ 处理后，Scu（10mg/2mL）或吡拉西坦（10mg/2mL）每天灌胃 20 天。采用 Morris 水迷宫试验评估学习记忆能力。采用 Western blot 和实时 PCR 分别检测脑内烟碱型乙酰胆碱受体（nAChR）α4、α7 和β2 亚基的蛋白和 mRNA 水平。采用 Ellman 比色法测定脑和血浆中乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的活性。
与对照组和假手术组相比，Aβ 组的逃避潜伏期和首次平台穿越明显延长，平台穿越总次数明显减少。Scu 和吡拉西坦治疗均可显著缩短逃避潜伏期和穿越平台时间，增加平台穿越次数，但 Aβ+Scu 组与 Aβ+吡拉西坦组之间无显著差异。与对照组和假手术组相比，Aβ 组皮质 nAChR α4 和 α7 亚基蛋白水平分别下降 42%-47%和 58%-61%。Scu 处理可使 α4 和 α7 亚基蛋白分别上调约 24%和 30%，但 Aβ+Scu 组与 Aβ+吡拉西坦组之间无显著差异。不同组间 nAChR β2 亚基蛋白水平无显著差异。nAChR α4、α7 和 β2 亚基的 mRNA 水平无明显变化。与对照组和假手术组相比，Aβ 组脑内 AChE 和 BuChE 活性显著升高，而血浆中 AChE 和 BuChE 活性显著降低。Scu 或吡拉西坦治疗使脑和血浆中的酶活性恢复至接近对照组水平。
这些结果提示，Scu 可能通过刺激 nAChR 蛋白翻译和调节胆碱酯酶活性来挽救 Aβ 的一些有害作用。
