Department of Pharmacology, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang, 712046, People's Republic of China.
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, China Pharmaceutical University, 639# Longmian Road, Jiangsu, Nanjing, 210009, People's Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct;396(10):2637-2650. doi: 10.1007/s00210-023-02486-6. Epub 2023 Apr 25.
This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40 mg/kg), and high-dose (80 mg/kg) astragaloside IV. After 30 days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water maze and then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin-eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels.
本研究旨在观察黄芪甲苷对糖尿病认知功能障碍（DCI）大鼠胃饥饿素的上调作用，并探讨通过降低氧化应激来防治的途径。DCI 模型采用链脲佐菌素（STZ）联合高脂高糖饮食诱导，分为三组：模型组、低剂量（40mg/kg）和高剂量（80mg/kg）黄芪甲苷组。灌胃 30 天后，采用 Morris 水迷宫测试大鼠学习记忆能力以及体质量和血糖水平，检测胰岛素抵抗、SOD 活性和血清 MDA 水平。取大鼠全脑进行苏木精-伊红和尼氏染色，观察海马 CA1 区的病理变化。免疫组化检测海马 CA1 区胃饥饿素表达。Western blot 检测 GHS-R1α/AMPK/PGC-1α/UCP2 变化。RT-qPCR 检测胃饥饿素 mRNA 水平。黄芪甲苷减轻神经损伤，增加超氧化物歧化酶（SOD）活性，降低 MDA 水平，改善胰岛素抵抗。血清和海马组织中胃饥饿素水平和表达增加，大鼠胃组织中胃饥饿素 mRNA 水平增加。根据 Western blot，它增加了胃饥饿素受体 GHS-R1α 的表达，并上调了与线粒体功能相关的蛋白 AMPK-PGC-1α-UCP2。黄芪甲苷通过增加脑内胃饥饿素的表达来减轻氧化应激，延缓糖尿病引起的认知功能障碍。这可能与促进胃饥饿素 mRNA 水平有关。
