Wang Bo, Lian Yong-Jie, Dong Xin, Peng Wei, Liu Lin-Lin, Su Wen-Jun, Gong Hong, Zhang Ting, Jiang Chun-Lei, Li Jia-Si, Wang Yun-Xia
Lab of Stress Medicine, Department of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China.
Lab of Stress Medicine, Department of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China; Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Behav Brain Res. 2018 Nov 1;353:250-257. doi: 10.1016/j.bbr.2018.01.024. Epub 2018 Jan 31.
Our previous study implied the role of central high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-induced depressive-like behaviors that could partially abrogate by glycyrrhizic acid (GZA). Here, we considered the potential mechanism underlying GZA ameliorating chronic stress-induced depression both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS) mice. Sucrose preference test, tail suspension test and open field test were performed to reflect depressive-like behaviors. Enzyme activity of indoleamine-2,3-dioxygenase (IDO) was recorded with the ratio of kynurenine (KYN) / tryptophan (Trp). Transcription of gene was evaluated by RT-PCR. Along with depressive-like behaviors, IDO, the rate-limiting enzyme of the kynurenine pathway (KP), was upregulated at the level of mRNA expression, and enzyme activity was also elevated in stressed hippocampi and LPS/HMGB1-treated hippocampus slices. Treatment of mice with GZA, the inhibitor of HMGB1, prevented the activated enzymes in KP and the development of depressive-like behaviors. These experiments demonstrate that GZA may restrain HMGB1 thus improving chronic stress-induced depressive behavior through regulating KP.
我们之前的研究表明，中枢高迁移率族蛋白B1（HMGB1）在脂多糖（LPS）诱导的抑郁样行为中发挥作用，而甘草酸（GZA）可部分消除这种作用。在此，我们探讨了GZA在体内和体外改善慢性应激诱导的抑郁症的潜在机制。采用4周慢性不可预测轻度应激（CUMS）小鼠建立抑郁症模型。通过蔗糖偏好试验、悬尾试验和旷场试验来反映抑郁样行为。通过犬尿氨酸（KYN）/色氨酸（Trp）的比值记录吲哚胺-2,3-双加氧酶（IDO）的酶活性。通过逆转录-聚合酶链反应（RT-PCR）评估基因转录。随着抑郁样行为的出现，犬尿氨酸途径（KP）的限速酶IDO在mRNA表达水平上调，并且在应激海马体和LPS/HMGB1处理的海马体切片中酶活性也升高。用HMGB1抑制剂GZA处理小鼠可阻止KP中酶的激活以及抑郁样行为的发展。这些实验表明，GZA可能通过抑制HMGB1，从而通过调节KP来改善慢性应激诱导的抑郁行为。
