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大鼠高血压性脑白质病变中的脑功能与异常β-淀粉样蛋白蓄积。

Brain functions and unusual β-amyloid accumulation in the hypertensive white matter lesions of rats.

机构信息

Department of Cardiology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihaer City, Heilongjiang Province, China.

Electrophysiology Science, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihaer City, Heilongjiang Province, China.

出版信息

J Biol Regul Homeost Agents. 2019 Jul-Aug;33(4):1073-1084.

Abstract

This study used Sprague Dawley (SD) rats with stroke-prone renovascular hypertension (RHRSP) to establish an animal model of hypertensive white matter lesions (WML), so as to explore the brain functions and unusual β-amyloid (Aβ) accumulation in WML. Hypertensive WML and brain dysfunctions were evaluated by measuring the caudal arterial pressure of model rats, and by observing the histomorphological deformations o f the prefrontal lobe, temporal lobe, hippocampus and corpus callosum, as well as by counting of the number of neurons using Hematoxylin and Eosin (H and E) staining, and by evaluating the changes in rat brain functions, including memory and the ability of visual space learning, using the Morris Water Maze Test. In addition, the study discussed the correlation between Aβ accumulation and hypertensive WML cognitive impairment by adopting an enzyme-linked immunosorbent assay (ELISA) to detect the level of Aβ 1-42, and by detecting the expression of amyloid precursor protein (APP) and Beta-secretase 1 (BACE1) using Western blot. Results of the study showed that at 4 weeks, 8 weeks, 12 weeks and 16 weeks after operation, the blood pressure and brain Aβ expression in the rats of the model group notably increased (P less than 0.01), along with deformed and degenerated brain tissues, confirming that the unusual Aβ accumulation may participate in the occurrence and development of hypertensive WML as well as the induction of cerebral cognitive decreases.

摘要

本研究采用易发生卒中的自发性高血压大鼠(SHRSP)构建高血压性脑白质病变(WML)动物模型,探讨 WML 脑功能及异常β-淀粉样蛋白(Aβ)沉积。通过检测模型大鼠尾动脉压,观察额叶、颞叶、海马和胼胝体组织形态学改变,H&E 染色计数神经元数量,评价大鼠脑功能改变,包括记忆和视觉空间学习能力,采用 Morris 水迷宫试验,评价高血压性 WML 及脑功能障碍。另外,通过酶联免疫吸附试验(ELISA)检测 Aβ1-42 水平,采用 Western blot 检测淀粉样前体蛋白(APP)和β-分泌酶 1(BACE1)表达,探讨 Aβ 沉积与高血压性 WML 认知障碍的相关性。结果显示,术后 4 周、8 周、12 周、16 周时模型组大鼠血压及脑内 Aβ 表达明显升高(P 均<0.01),同时伴有脑组织变形、变性,提示异常 Aβ 沉积可能参与高血压性 WML 的发生发展及脑认知下降的诱导。

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