抑郁症气虚证候模型小鼠的药物反证与分子信号研究
The Pharmacological Validation of Qi-Deficiency Syndrome with Chinese Herbal Medicine in a Depression Model and an Associated Molecular Biology Study in Female Balb/c Strain Mice
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摘要: 对Balb/c小鼠在单独抑郁症疾病造模条件下的气虚证候表现进行方药反证,并探究病证相关的分子生物学基础。方法 对Balb/c雌性小鼠进行慢性不可预知轻度应激(CUMS)造模,通过旷场、糖偏好、新奇环境摄食等评判其抑郁样疾病表现,通过负重游泳、掌纹血色度、抓力、皮毛评分等评判气虚样表现,给予补气经典方四君子汤进行方药反证并观测病证疗效,用Western blot法检测各组海马与肌肉组织中PKA、p-CREB的表达变化。结果 四君子汤改善模型小鼠抓力下降、负重游泳时间减少、皮毛评分增加的气虚样证候,也逆转了糖偏好下降等抑郁样表现,而且逆转模型动物海马和肌肉PKA、p-CREB表达的下调。结论 在CUMS下Balb/c小鼠产生抑郁症样行为及气虚样证候,均被补气方药四君子汤的疗效所反证,这可能是通过改善外周和脑PKA-CREB信号通路发挥作用。结果支持Balb/c小鼠的气虚证候易感的特性和辨证论治治疗疾病的有效性。Abstract: OBJECTIVE This study focused on the verification of the the TCM Qi-defiency syndrome and depression-like behavior in Balb/c mice following chronic unpredictable mild stress (CUMS), and the underlying molecular biology of disease-syndrome association. METHODS CUMS was used to induce depression on the female Balb/c mice. Sijunzi Decoction (SJZD) was administrated to mice and the syndromes were verified based on pharmacological effect. We assessed the behaviors of depression in the mice by open field test (OFT), sucrose preference test (SPT) and novelty suppressed feeding (NSF). We assessed the Qi-deficiency phenotype by exhausted swim test, degree of redness, grip strength and fur condition. The changes of PKA-CREB signaling in muscle and hippocampus of mice were observed via Western blot. RESULTS SJZD improved Qi-deficiency like syndromes of Balb/c mice by reversing deficits in grip strength, exhausted swim test and increased fur score. SJZD also reversed depressive like behaviors by increasing the sucrose preference and so on. The decreased phosphorylation of the CREB (p-CREB) and PKA expression of hippocampus and muscle in CUMS mice were reversed by SJZD. CONCLUSION Follwing CUMS, Balb/c mice displayed depression-like behavior and Qi deficiency-like syndromes, both of which were rescued by using the Qi-tonifying formula SJZD. Improving PKA-CREB signaling in periphery and brain may be an essential mechanism. The findings supported the susceptibility to the Qi-deficiency syndrome of Balb/c mouse strain, and the validality of TCM treatment of diseases based on syndrome.
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Key words:
- depression /
- Balb/c /
- CUMS /
- Qi deficiency /
- PKA-CREB /
- disease and TCM syndrome association
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