Institute of Integrative Medicine, Dalian Medical University, Dalian, 116044, Liaoning, China.
Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, Liaoning, China.
J Ethnopharmacol. 2023 Feb 10;302(Pt B):115947. doi: 10.1016/j.jep.2022.115947. Epub 2022 Nov 17.
Zibu Piyin Recipe (ZBPYR) is a traditional Chinese medicine compound composed of 12 kinds of Chinese herbal medicines including red ginseng and yam. Long-term basic and clinical applications have proved that ZBPYR can prevent and treat cognitive dysfunction. Previous studies showed that chronic psychological stress can increase the risk of type 2 diabetes mellitus (T2DM), and lead to cognitive decline. Mitochondrial dysfunction plays a key role in chronic psychological stress-induced diabetes mellitus. While the mechanism of mitochondrial dysfunction and insulin resistance in diabetes-associated cognitive decline (DACD) is unclear.
Our previous research found that a ZiBuPiYin recipe (ZBPYR) has significant pharmacological effects against DACD. The present study investigated changes in mitochondrial dysfunction in the brain and the mechanism of insulin resistance and mitochondrial damage to explore the relationship between neuronal mitochondrial dysfunction and insulin resistance in chronic psychologically stressed DACD rats.
Zucker diabetic fatty (ZDF) rats with spontaneous T2DM and rats with diabetic cognitive impairment that was induced by chronic psychological stress were used in in vivo experiments. PC12 cells that were damaged by rotenone were used for the in vitro experiment.
The findings indicated that the number of mitochondria decreased, morphology and membrane potential were damaged, and reactive oxygen species increased in the cortex and hippocampus in psychologically stressed DACD rats. Protein kinase Cβ2 (PKCβ2) activation and insulin resistance were markedly induced by chronic psychological stress, together with decreases in peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial fusion protein 2 (Mfn2). Furthermore, ZBPYR exerted protective effects both in in vivo and in vitro.
Mitochondrial damage and insulin resistance were observed in the brain in chronic psychologically stressed DACD rats. The ZBPYR significantly improved brain mitochondrial damage and insulin resistance in chronic psychologically stressed DACD rats. These results provide novel insights for the development of ZBPYR as a traditional Chinese medicine for the treatment of chronic psychological stress and DACD.
自拟平喘饮（ZBPYR）是一种由 12 种中草药组成的中药复方，包括红参和山药。长期的基础和临床应用证明，ZBPYR 可以预防和治疗认知功能障碍。先前的研究表明，慢性心理应激会增加 2 型糖尿病（T2DM）的风险，并导致认知能力下降。线粒体功能障碍在慢性心理应激诱导的糖尿病中起着关键作用。然而，糖尿病相关认知障碍（DACD）中线粒体功能障碍和胰岛素抵抗的机制尚不清楚。
我们之前的研究发现，自拟平喘饮（ZBPYR）对 DACD 具有显著的药理作用。本研究旨在探讨脑线粒体功能障碍的变化及胰岛素抵抗和线粒体损伤的机制，以探讨慢性心理应激性 DACD 大鼠神经元线粒体功能障碍与胰岛素抵抗的关系。
体内实验采用自发性 2 型糖尿病 Zucker 糖尿病肥胖（ZDF）大鼠和慢性心理应激诱导的糖尿病认知障碍大鼠，体外实验采用鱼藤酮损伤的 PC12 细胞。
研究结果表明，慢性心理应激性 DACD 大鼠皮质和海马区线粒体数量减少，形态和膜电位受损，活性氧增加。慢性心理应激明显诱导蛋白激酶 Cβ2（PKCβ2）激活和胰岛素抵抗，同时降低过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）和线粒体融合蛋白 2（Mfn2）。此外，ZBPYR 在体内和体外均具有保护作用。
慢性心理应激性 DACD 大鼠脑内存在线粒体损伤和胰岛素抵抗。ZBPYR 显著改善慢性心理应激性 DACD 大鼠脑线粒体损伤和胰岛素抵抗。这些结果为开发 ZBPYR 作为治疗慢性心理应激和 DACD 的中药提供了新的思路。
