School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China; Key Laboratory of Liaoning Province for TCM Spleen-Viscera-State Modern Research, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118808. doi: 10.1016/j.jep.2024.118808. Epub 2024 Sep 17.
Cognitive impairment caused by central neuropathy in type 2 diabetes mellitus (T2DM), namely diabetes-associated cognitive decline (DACD), is one of the common complications in patients with T2DM. Studies have shown that brain β-amyloid (Aβ) deposition is a typical pathological change in patients with DACD, and that there is a close relationship between intestinal microorganisms and cognitive impairment. However, the specific mechanism(s) of alteration in Aβ metabolism in DACD, and of the correlation between Aβ metabolism and intestinal microorganisms remain unknown.
Revealing the mechanism of ZBPYR regulating Aβ metabolism and providing theoretical basis for clinical evaluation and diagnosis of DACD.
We characterized Aβ metabolism in the central and peripheral tissues of Zucker diabetic fatty (ZDF) rats with DACD, and then explored the preventive and therapeutic effects of ZiBu PiYin Recipe (ZBPYR). Specifically, we assessed these animals for the formation, transport, and clearance of Aβ; the morphological structure of the blood-brain barrier (BBB); and the potential correlation between Aβ metabolism and intestinal microorganisms.
ZBPYR provided improvements in the structure of the BBB, attenuation of Aβ deposition in the central and peripheral tissues, and a delay in the development of DACD by improving the expression of Aβ production, transport, and clearance related protein in ZDF rats. In addition, ZBPYR improved the diversity and composition of intestinal microorganisms, decreased the abundance of Coprococcus, a bacterium closely related to Aβ production, and up regulate the abundance of Streptococcus, a bacterium closely related to Aβ clearance.
The mechanism of ZBPYR ability to ameliorate DACD may be closely related to changes in the intestinal microbiome.
2 型糖尿病（T2DM）引起的中枢神经病变导致的认知障碍，即糖尿病相关认知障碍（DACD），是 T2DM 患者的常见并发症之一。研究表明，脑β-淀粉样蛋白（Aβ）沉积是 DACD 患者的典型病理变化，肠道微生物与认知障碍之间存在密切关系。然而，DACD 中 Aβ代谢改变的具体机制以及 Aβ代谢与肠道微生物之间的相关性尚不清楚。
揭示 ZBPYR 调节 Aβ代谢的机制，为临床评估和诊断 DACD 提供理论依据。
我们对患有 DACD 的 Zucker 糖尿病肥胖（ZDF）大鼠的中枢和外周组织中的 Aβ代谢进行了特征描述，然后探讨了 ZiBuPiYinRecipe（ZBPYR）的预防和治疗作用。具体而言，我们评估了这些动物的 Aβ形成、转运和清除情况；血脑屏障（BBB）的形态结构；以及 Aβ代谢与肠道微生物之间的潜在相关性。
ZBPYR 通过改善 ZDF 大鼠中与 Aβ产生、转运和清除相关的蛋白表达，改善了 BBB 的结构，减轻了中枢和外周组织中 Aβ的沉积，并延缓了 DACD 的发展。此外，ZBPYR 改善了肠道微生物的多样性和组成，降低了与 Aβ产生密切相关的 Coprococcus 的丰度，并上调了与 Aβ清除密切相关的 Streptococcus 的丰度。
ZBPYR 改善 DACD 的机制可能与肠道微生物群的变化密切相关。
