逐痰通络汤治疗脑卒中后抑郁的作用机制研究

The Effects and Mechanism of ZTTLT on PSD Animals

摘要: 目的：观察逐痰通络汤对急性及慢性卒中后抑郁(PSD)模型小鼠、大鼠行为学及各脑区单胺递质、单胺氧化酶、腺苷酸环化酶的影响。方法：急性实验：90只清洁级昆明种小鼠，随机分为正常对照组，逐痰通络汤组(1 g/kg，2 g/kg，4 g/kg，8 g/kg)，阳性对照组(氟西汀10 mg/kg)，每组15只。用栓线法建立局灶性脑缺血再灌注小鼠模型，通过强迫游泳，悬尾实验对小鼠行为学评价，采用高效液相法，检测小鼠不同脑区单胺递质及其代谢产物的水平(5-HT、DA、NE、5-HIAA、DOPAC)及单胺氧化酶A和单胺氧化酶B的活性。慢性实验：90只清洁SD大鼠，随机分为正常对照组，应激模型组，逐痰通络汤组(2 g/kg，4 g/kg，8 g/kg)，阳性对照组(氟西汀10 mg/kg)，每组15只，用栓线法建立局灶性脑缺血再灌注小鼠模型，叠加慢性不可预见性刺激与孤养结合造成PSD动物模型，通过开野实验，穿梭箱实验对大鼠行为学评价，采用放射免疫法，测量大鼠不同脑区AC活性。结果：急性实验：逐痰通络汤2~8 g∙kg−1均能降低小鼠两个行为学测试中的不动时间(P < 0.01)，不影响小鼠自主活动(P > 0.05)，能够显著增加海马和前额叶中5-HT和NE的水平(P < 0.05)，但是对DA、DOPAC含量无明显变化(P > 0.05)，均不影响下丘脑和纹状体的单胺递质含量(P > 0.05)，高剂量逐痰通络汤可以降低海马和前额叶中5-HIAA/5-HT比率(P < 0.05)，可以下调海马和前额叶单胺氧化酶A活性(P < 0.01)。慢性实验：逐痰通络汤2~8 g∙kg−1均对大鼠行为学测试开野实验和穿梭箱失败实验有一定改善，能够显著增加海马和皮层中AC活性。结论：逐痰通络汤的抗抑郁作用与海马和前额叶皮层内的5-HT浓度、NE浓度、AC活性有关。上述脑区中单胺氧化酶A活性的抑制对增加单胺递质含量及逐痰通络汤的抗抑郁样活性起了重要的作用。

Abstract: Object: To explore the possible mechanism and analyze the effect of ZTTLT decoction in improving the PSD-like symptom. The PSD model was established by time dependent sensitivity stress (TDS) in rats. Behavioral tests were performed as described, including the locomotor activity test, the shuttle box test, the tail suspension test (TST) and the force swimming test (FST). Moreover, the monoamino transmitters including 5-HT, NE, DA and their metabolites of 5-HIAA, DOPAC in different regions of brain, and the MAO-A and MAO-B levels were detected to analyze the effects of ZTTLT decoction. Radioimmunoassay analyzed the expression of the AC in different regions of brain. The results of FST, TST and shuttle box test indicated that model group mice or rats showed weak desire for exploration with depression-like symptom. These PSD-associated behavior abnormalities induced by TDS exposure were ameliorated after treatment with ZTTLT decoction. The results of the concentrations of monoamino transmitters in different regions of brain showed that ZTTLT decoction treatment reversed the abnormal levels of neurotransmitters above. These findings also indicated that ZTTZL decoction may exert the effects on PSD-like mice or rats induced by TDS through regulating the levels of neurotransmitters and AC.