叶片中的类黄酮可调节由复合 Aβ诱导的大鼠脑中多个部位的 Tau 过度磷酸化。
Flavonoids from Stems and Leaves of Regulate the Brain Tau Hyperphosphorylation at Multiple Sites Induced by Composited Aβ in Rats.
机构信息
Institute of Traditional Chinese Medicine, Chengde Medical College, An Yuan Road, Chengde Medical College, Chengde, China.
出版信息
CNS Neurol Disord Drug Targets. 2022;21(4):367-374. doi: 10.2174/1871527320666210827112609.
BACKGROUND
Neurofibrillary Tangles (NFTs), formed by hyperphosphorylation of Tau protein in Alzheimer's Disease (AD), arethe main pathomechanisms of neuronal degeneration, which indicate a sign of brain disorder. NFTs are positively correlated with the degree of cognitive impairment in AD.
OBJECTIVE
The objective of this study isto investigate the effect of flavonoids from the stems and leaves of (SSF) on the hyperphosphorylated expression levels at multiple sites of Tau protein induced by β-amyloid protein 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ) in rats.
METHODS
The AD rat models were established by intracerebroventricular injection of Aβ25-35 and AlCl3 combined with RHTGF-β1. On day 45, after the operation, the Morris water maze test was conducted to screen the memory impairment of AD models. The successful model rats were randomly divided into the model group and the three-dose drug group. The drug group rats were orally administered SSF daily for 38 days. Western blotting was performed to detect the protein expression of P-Tau (Thr 181), P-Tau (Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-- Tau (Ser 396), and P-Tau (Ser 404) in the hippocampus and cerebral cortex of rats.
RESULTS
Compared with the sham group, the expression of P-Tau (Thr 181), P-Tau (Thr 217), P-- Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser 404)was significantly increased in the hippocampus and cerebral cortex of the model group (P < 0.01). However, the three doses of SSF, ., 35, 70, and 140 mg/kg, regulated the expression of phosphorylated Tau proteinto varying degrees in the hippocampus and cerebral cortex of AD model rats (P < 0.01).
CONCLUSION
SSF could significantly reduce the protein expression levels of P-Tau (Thr 181), PTau (Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser 404), induced by the intracerebroventricular injection of composited Aβ, in rats' brain. These results indicated that the neuro-protection and the improvement in the impaired memory of rats by SSF were due to the inhibition of hyperphosphorylation of Tau protein at multiple sites in rats' brain.
背景
神经原纤维缠结（NFTs）是由 Tau 蛋白在阿尔茨海默病（AD）中的过度磷酸化形成的，是神经元退化的主要发病机制，表明大脑紊乱的迹象。NFTs 与 AD 患者认知障碍的严重程度呈正相关。
目的
本研究旨在探讨柳枝稷茎叶黄酮（SSF）对β-淀粉样蛋白 25-35（Aβ25-35）与三氯化铝（AlCl3）和重组人转化生长因子-β1（RHTGF-β1）（复合 Aβ）联合诱导的 Tau 蛋白多个位点过度磷酸化表达水平的影响。
方法
通过侧脑室注射 Aβ25-35 和 AlCl3 联合 RHTGF-β1 建立 AD 大鼠模型。术后第 45 天，进行 Morris 水迷宫试验筛选 AD 模型的记忆障碍。成功建立 AD 模型的大鼠随机分为模型组和三个剂量药物组。药物组大鼠每日灌胃 SSF，连续 38 天。Western blot 检测大鼠海马和皮质中 P-Tau（Thr181）、P-Tau（Thr217）、P-Tau（Thr231）、P-Tau（Ser199）、P-Tau（Ser235）、P-Tau（Ser396）和 P-Tau（Ser404）的蛋白表达。
结果
与假手术组相比，模型组大鼠海马和皮质中 P-Tau（Thr181）、P-Tau（Thr217）、P-Tau（Thr231）、P-Tau（Ser199）、P-Tau（Ser235）、P-Tau（Ser396）和 P-Tau（Ser404）的表达明显增加（P<0.01）。然而，SSF 的三个剂量，即 35、70 和 140mg/kg，在不同程度上调节了 AD 模型大鼠海马和皮质中磷酸化 Tau 蛋白的表达（P<0.01）。
结论
SSF 可显著降低复合 Aβ 脑室内注射诱导的大鼠大脑中 P-Tau（Thr181）、PTau（Thr217）、P-Tau（Thr231）、P-Tau（Ser199）、P-Tau（Ser235）、P-Tau（Ser396）和 P-Tau（Ser404）的蛋白表达水平。这些结果表明，SSF 对大鼠脑内多个部位 Tau 蛋白过度磷酸化的抑制作用，导致了其对大鼠的神经保护和记忆损伤的改善。
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