Department of Neurology, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, 272000, Shandong, People's Republic of China.
Neurochem Res. 2018 Apr;43(4):972-983. doi: 10.1007/s11064-018-2503-1. Epub 2018 Mar 1.
Patients with diabetes mellitus are easy to experience diabetic encephalopathy (DE) and other cognition dysfunction, whereas the neural alterations in developing this disease are unknown yet. Chrysophanol (CHR) is one of traditional Chinese medicine which was reported to show protective effects in cognition dysfunction and inflammatory in previously studies. In this current study, whether CHR protects learning and memory dysfunctions induced by diabetes disease or not and underlying mechanisms were studied. DE model was induced by streptozotocin (STZ, i.p.) in ICR mice. CHR was administrated 3 days after STZ treated mice which was confirmed with diabetes for consecutive 6 days. Learning and memory function was tested by Morris water maze after the CHR injection. The morphology of neuronal cells in hippocampus CA3 region was stained by HE-staining. ELISA and Western blot assay were used to determine the levels of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus. Here, we demonstrated that mice harboring diabetes mellitus induced by STZ exhibit high blood glucose, learning and memory deficits detected by Morris water maze behavior tests. Application with CHR right after developing diabetes disease rescues partial blood sugar increasing, learning and memory deficits. The data also indicated that the death rate of neurons and the number of astrocytes in hippocampus CA3 region was significantly improved in diabetic mice. Moreover, the underlying mechanisms of CHR's protective effect are likely associated with anti-inflammation by downregulating the expression of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus and inhibiting the over-activation of astrocytes in hippocampus CA3 region. Therefore, application with CHR contributes to the learning and memory deficits induced by diabetes disease via inhibitory expressions of inflammatory in hippocampus region.
患有糖尿病的患者容易出现糖尿病性脑病(DE)和其他认知功能障碍,而这种疾病发展过程中的神经改变尚不清楚。大黄素(CHR)是一种中药,先前的研究表明它在认知功能障碍和炎症中具有保护作用。在本研究中,研究了 CHR 是否可以预防糖尿病引起的学习和记忆功能障碍及其潜在机制。通过腹腔注射链脲佐菌素(STZ)在 ICR 小鼠中诱导 DE 模型。在 STZ 处理后 3 天,即确认糖尿病后连续 6 天,给予 CHR 治疗。CHR 注射后通过 Morris 水迷宫测试学习和记忆功能。通过 HE 染色观察海马 CA3 区神经元细胞的形态。ELISA 和 Western blot 测定海马中促炎细胞因子(IL-1β、IL-4、IL-6、TNF-α)的水平。结果表明,STZ 诱导的糖尿病小鼠表现出血糖升高、Morris 水迷宫行为测试检测到的学习和记忆功能缺陷。糖尿病发病后立即应用 CHR 可部分挽救血糖升高和学习记忆障碍。数据还表明,糖尿病小鼠海马 CA3 区神经元死亡率和星形胶质细胞数量显著改善。此外,CHR 的保护作用的潜在机制可能与通过下调海马中促炎细胞因子(IL-1β、IL-4、IL-6、TNF-α)的表达和抑制海马 CA3 区星形胶质细胞的过度激活来抑制炎症有关。因此,CHR 的应用通过抑制海马区的炎症反应,有助于改善糖尿病引起的学习和记忆障碍。