Department of Nephrology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
Department of Traditional Chinese Medicine, Chongqing General Hospital, Chongqing, China.
Front Endocrinol (Lausanne). 2023 Jun 27;14:1206353. doi: 10.3389/fendo.2023.1206353. eCollection 2023.
Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear.
In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors.
CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice.
Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study.
柴胡龙骨牡蛎汤（CLMD）是一种古老的方剂，最初记录在中医理论奠基人张仲景所著的《伤寒论》中。虽然它被广泛用于治疗神经精神疾病，如失眠、焦虑和痴呆症，但它的作用机制尚不清楚。
为了分析 CLMD 在慢性肾衰竭和失眠中的治疗机制，我们在小鼠中建立了腺嘌呤饮食诱导的慢性肾脏病（CKD）模型，此外，我们还分析了 CLMD 对 CKD 小鼠睡眠行为和认知功能的影响，以及与失眠相关的调节蛋白和炎症因子的产生。
CLMD 显著改善了 CKD 小鼠的昼夜节律和睡眠障碍。CKD 小鼠下丘脑的失眠相关调节蛋白 Orexin、Orexin R1 和 Orexin R2 明显下降，而 CLMD 干预后 Orexin 和其受体显著增加。给予 CLMD 后，CKD 小鼠的神经元丢失减少，学习和记忆能力得到改善。CLMD 干预有效改善了 CKD 小鼠的慢性炎症状态。
我们的结果表明，CLMD 可以改善 CKD 小鼠的睡眠和认知水平。其机制可能与 Orexin-A 的上调和 CaMKK2/AMPK 的磷酸化水平增加有关，这进一步抑制了 NF-κB 下游信号通路，从而改善了中枢和外周系统中失调的炎症状态。然而，需要进一步的研究来证实本研究的临床意义。
