百事乐加味方对脑卒中后抑郁症大鼠海马-前额叶皮层环路炎症平衡的影响

目的研究百事乐加味方(MBD)对脑卒中后抑郁症(Post-stroke depression,PSD)大鼠炎症因子IL-1β、IL-6、TNF-α含量及海马(HP)、前额叶皮层(PFC)组织NF-κB表达水平的影响,从炎症平衡角度探讨复方中药防治该病可能机制。方法采用MCAO+CUMS+孤养法复合因素建立PSD模型,记录大鼠每周体重;采用ELISA方法,检测PSD大鼠血清炎症因子IL-1β、IL-6和TNF-α的含量;采用免疫组化技术检测HP、PFC组织NF-κB的表达水平。结果对体质量影响,与PSD大鼠比较,MBD组在应激第14、21、28天能够恢复模型大鼠体重,差异具有统计学意义(P<0.01~0.05);对炎症相关指标影响,与PSD大鼠比较,MBD高剂量组明显降低大鼠血清中IL-1β,IL-6、TNF-α含量,明显降低大鼠HP、PFC组织NF-κB水平,差异有统计学意义(P<0.01~0.05);MBD低剂量组明显降低大鼠血清中IL-6,TNF-α含量及大鼠HP、PFC组织NF-κB表达水平,差异有统计学意义(P<0.05)。与卒中组比较,MBD高剂量组明显降低大鼠血清中IL-1β、IL-6含量,同时降低HP、PFC组织NF-κB的表达水平,差异有统计学意义(P<0.05);低剂量治疗组HP、PFC组织NF-κB水平明显降低,差异有统计学意义(P<0.01~0.05)。与抑郁组比较,MBD高剂量组明显降低大鼠血清中IL-1β含量,HP、PFC组织NF-κB的表达水平明显降低,差异有统计学意义(P<0.01~0.05);MBD低剂量组HP、PFC组织的NF-κB表达水平略降低,但差异不具有统计学意义(P>0.05)。结论 MBD能有效抑制PSD大鼠相关炎症反应因子,同时降低HP、PFC组织NF-κB表达水平,改善PSD大鼠脑神经功能,从而发挥治疗作用,是其抗脑卒中后抑郁重要机制之一。

Effect of Baishile MBD Decoction on Inflammatory Balance of Hippocampus-Prefrontal Cortex Circuit in Post-stroke Depression Rats

Objective To study the effect of Modified Baishile Decoction(MBD) on the contents of IL-1β,IL-6 and TNF-α and the expression of NF-κB in hippocampal prefrontal cortex in rats with post-stroke depression. To explore the possible mechanism of compound Chinese medicine preventing and treating the disease from inflammatory balance. Methods The rat model of focal cerebral ischemia was established by the method of middle cerebral artery occlusion(MCAO), and the PSD model was established by combining with unpredictable mild stress(CUMS) and solitary nourishment. The weekly body weight of rats was recorded. The contents of IL-1β,IL-6 and TNF-α in serum of PSD rats were determined by ELISA method. The expression of NF-κB in hippocampus and prefrontal cortex was detected by immunohistochemistry. Results The effects of weight:Compared with PSD rats, the rats in the treatment group were able to recover the weight of the model rats on the 14 th,21 st and 28 th day after stress. The difference was statistically significant(P<0.01). Impact on inflammation related indicators:Compared with PSD rats, the high-dose group significantly decreased the contents of IL-1β,IL-6 and TNF-α in serum and the level of NF-κB in hippocampus and prefrontal cortex of rats. The difference was statistically significant(P<0.01). In the low-dose group, the contents of IL-6 and TNF-α and the expression of NF-κB in hippocampus and prefrontal cortex were significantly decreased(P<0.05). Compared with the stroke group, the high-dose group significantly decreased the contents of IL-1β and IL-6 in serum and the expression of NF-κB in hippocampus and prefrontal cortex. The difference was statistically significant(P<0.05). The levels of NF-κB in the hippocampus and prefrontal cortex were significantly decreased in the low-dose treatment group(P<0.01,P<0.05). Compared with the depression group, the levels of IL-1β in the hippocampus and NF-κB in the serum were significantly lower than those in the high-dose group(P<0.01,P<0.05). In the low-dose group, the expression of NF-κB in hippocampus-prefrontal cortex circuit decreased slightly, but the difference was not statistically significant(P>0.05). Conclusion The Modified Baishile Decoction can effectively inhibit the inflammatory response factors in PSD rats. At the same time,it can reduce the expression level of NF-κB in hippocampus-prefrontal cortex circuit and improve the brain nerve function of PSD rats, and thus playing a therapeutic role. It is one of the important mechanisms of anti-stroke depression.