Study on the Changes in Brain Function Characteristics of Chaihu Tongbian Decoction in Rats with Slow Transit Constipation and Depression Based on Resting-State Functional Magnetic Resonance Imaging
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摘要:
目的 运用静息态功能磁共振成像(rs-fMRI)观察柴胡通便汤对慢传输型便秘(STC)伴抑郁大鼠的脑功能特征变化。 方法 70只健康SPF级雄性SD大鼠随机分为空白组, 模型组, 莫沙必利组, 盐酸氟西汀组, 柴胡通便汤低(11.02 g·kg-1)、中(22.05 g·kg-1)、高(44.1 g·kg-1)剂量组。采用复方苯乙哌啶片联合孤养结合慢性不可预见性温和应激法(CUMS)构建STC伴抑郁大鼠模型, 造模成功后给药处理。观察大鼠一般情况，计算大鼠24 h粪便总粒数、粪便含水量、肠道碳末推进率，行结肠组织HE染色及检测大鼠抑郁样行为。通过比较rs-fMRI低频振幅(ALFF)值, 探讨各组大鼠脑部神经元活动之间差异。 结果 与空白组相比, 模型组24 h粪便总粒数、粪便含水量、肠道碳末推进率明显下降(P < 0.01)。HE染色提示模型组结肠组织病变严重。旷场实验和糖水消耗提示模型组大鼠活动水平降低(P < 0.01), 出现焦虑抑郁样行为改变。rs-fMRI结果提示, 与空白组相比, 模型组右侧海马后外侧部ALFF值降低、左侧杏仁核ALFF值升高(P < 0.01)。与模型组相比, 治疗4周后, 莫沙必利组和柴胡通便汤各剂量组24 h粪便总粒数、粪便含水量、肠道碳末推进率均得到改善(P < 0.05);与模型组相比, 治疗4周后, 盐酸氟西汀组和柴胡通便汤各剂量组能够改善大鼠焦虑抑郁样行为(P < 0.05);与模型组相比, 治疗4周后, 盐酸氟西汀组和柴胡通便汤高剂量组能够升高右侧海马后外侧部ALFF值, 降低左侧杏仁核ALFF值(P < 0.05)。 结论 柴胡通便汤能够有效缓解STC伴抑郁大鼠便秘及抑郁症状, 其机制可能与激活右侧海马后外侧部, 抑制杏仁核活动相关。 -
关键词:
- 柴胡通便汤 /
- 慢传输型便秘 /
- 静息态功能磁共振成像 /
- 杏仁核
Abstract:OBJECTIVE To observe the changes in brain function characteristics of Chaihu Tongbian Decoction in rats with slow transit constipation (STC) and depression using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS 70 healthy SPF grade male SD rats were randomly divided into the blank group, model group, mosapride group, fluoxetine hydrochloride group, low (11.02 g·kg-1), medium (22.05 g·kg-1), and high (44.1 g·kg-1) dose Chaihu Tongbian Decoction groups. A rat model of STC with depression was constructed using compound diphenylephrine tablets combined with solitary confinement and chronic unpredictable mild stress (CUMS). Drugs were administered after successful modeling. The general condition of the rats was observed; 24 h total number of fecal particles, fecal water content and intestinal carbon end advance rate were calculated; HE staining of the colon tissue was performed; the depressive-like behavior of the rats was detected. By comparing rs-fMRI amplitude of low-frequency fluctuation (ALFF) values, the differences in neuronal activity in the brains of rats in each group were explored. RESULTS Compared with the blank group, the 24 h total number of fecal particles, fecal water content and intestinal carbon end advance rate in the model group were significantly reduced (P < 0.01). HE staining showed that the colon tissue lesions in the model group were severe. Open field experiment and sugar water consumption showed that the activity level of rats in the model group decreased (P < 0.01), and behavioral changes like anxiety and depression appeared. The rs-fMRI results showed that compared with the blank group, the ALFF value of the right posterolateral hippocampus in the model group decreased and the ALFF value of the left amygdala increased (P < 0.01). Compared with the model group, after 4 weeks of treatment, the 24 h total number of fecal particles, fecal water content, and intestinal carbon end advance rate in the mosapride group and each dose group of Chaihu Tongbian Decoction were improved (P < 0.05); compared with the model group, after 4 weeks of treatment, the fluoxetine hydrochloride group and each dose group of Chaihu Tongbian Decoction could improve the anxiety and depression-like behavior of rats (P < 0.05); compared with the model group, after 4 weeks of treatment, the fluoxetine hydrochloride group and the high-dose Chaihu Tongbian Decoction group could increase the ALFF value of the right posterolateral hippocampus and decrease the ALFF value of the left amygdala (P < 0.05). CONCLUSION Chaihu Tongbian Decoction can effectively relieve constipation and depressive symptoms in STC rats with depression, and its mechanism may be related to activating the right posterolateral hippocampus and inhibiting amygdala activity. -
图 1 各组大鼠碳末推进率比较
注: 与空白组比较, * *P < 0.01;与模型组比较, #P < 0.05。x±s, n=10。
Figure 1. Comparison of carbon end advance rates among different groups of rats
图 3 各组大鼠焦虑抑郁样行为比较
注: 与空白组比较, * *P < 0.01;与模型组比较, #P < 0.05;与盐酸氟西汀组比较, ▲P < 0.05。x±s, n=10。
Figure 3. Comparison of anxiety- and depression-like behaviors in different groups of rats
图 4 大鼠静息状态下ALFF值的差异脑区
注: 黄色区域表示各组在右侧海马后外侧部、左侧杏仁核ALFF存在差异；黄色条带表示F值。
Figure 4. Differential brain regions of resting-state ALFF
图 5 各组大鼠静息状态下ALFF值比较
注: 与空白组比较, * *P < 0.01;与模型组比较, #P < 0.05。x±s, n=10。
Figure 5. Comparison of resting-state ALFF of rats in each group
表 1 各组大鼠治疗前后24 h粪便总粒数及含水量比较(x±s, n=10)
Table 1. Comparison of total feces number and fecal water content of rats in each group before and after treatment (x±s, n=10)
组别 时间 24 h粪便总粒数 粪便含水量/% 空白组 治疗前 40.8±2.69 46.2±2.44 治疗后 40.2±2.83 46.0±2.11 模型组 治疗前 27.2±4.83** 24.8±6.19** 治疗后 29.9±4.48** 26.9±4.51** 莫沙必利组 治疗前 27.0±4.11 25.5±4.95 治疗后 35.6±2.63#▲ 39.6±3.27#▲ 盐酸氟西汀组 治疗前 28.2±4.21 26.8±5.07 治疗后 30.2±2.91** 25.1±5.24** 柴胡通便汤低剂量组 治疗前 27.8±2.89 24.9±3.6 治疗后 34.0±3.27# 37.3±2.54#▲ 柴胡通便汤中剂量组 治疗前 27.4±2.72 25.0±2.71 治疗后 35.5±2.51#▲ 40.3±2.49#▲ 柴胡通便汤高剂量组 治疗前 27.3±4.29 25.3±5.14 治疗后 39.0±2.90#▲ 44.3±3.30#▲ 注：与空白组比较, * *P < 0.01;与模型组比较, #P < 0.05;与治疗前比较, ▲P < 0.05。 
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表 2 大鼠在静息状态下ALFF值的差异脑区
Table 2. Differential brain regions of resting-state ALFF
脑区名 团块大小 峰值点MNI坐标 F x y z 右侧海马_后外侧部 17 47 -6 5 15.02# 左侧杏仁核 80 -38 -46 -21 15.32# 注: MNI.蒙特利尔坐标系; #P < 0.05。
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