Zhang Tian, Wang Jiexin, Wang Yi, He Linxi, Lv Shangbin, Wang Yiran, Li Weihong
Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Neuropsychiatr Dis Treat. 2024 Mar 22;20:631-647. doi: 10.2147/NDT.S445636. eCollection 2024.
Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms.
We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB.
The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression.
This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats.
慢性炎症是抑郁症的关键机制之一。温阳-填精-解郁方(WTJD)是在诊疗过程中发现的一种有效的抗抑郁剂,但其治疗作用机制尚不清楚。本研究旨在评估WTJD对肾阳虚(KYD)型抑郁症大鼠的疗效并揭示其作用机制。
我们选取40只6周龄雄性Sprague-Dawley大鼠用于本研究。我们首先建立KYD(黄柏溶液灌胃并置于4°C环境;8周)型抑郁症(慢性不可预测温和刺激;6周)大鼠模型。造模成功后,我们对大鼠使用WTJD或氟西汀治疗3周。然后我们评估抑郁和KYD行为。最后,我们观察外周血和海马中关键炎症因子和蛋白的表达,并进一步研究Th17/Treg和Th1/Th2细胞的免疫平衡及其主要调控途径JAK2/STAT3和TLR4/TRAF6/NF-κB的活性。
大鼠Th17/Treg和Th1/Th2细胞失衡与KYD和抑郁症状相关。通过本研究,我们发现WTJD可抑制JAK2/STAT3和TLR4/TRAF6/NF-κB途径的活性,平衡Th17/Treg和Th1/Th2细胞稳态,调节海马和外周血中炎症因子水平,并逆转KYD和抑郁状态。
本研究证实WTJD对KYD抑郁症大鼠有可靠疗效,其机制是调节海马T细胞免疫稳态及相关炎症因子,以改善大鼠的KYD和抑郁症状。