人参-玉竹药对改善抑郁伴认知障碍机制研究

Ginseng and Polygonatum Medicine for Improving Mechanisms of Depression with Cognitive Impairment

目的通过分析人参-玉竹药对对抑郁大鼠海马PI3K、ICAM-1、MCP-1表达的影响,研究人参-玉竹药对改善抑郁症认知障碍的作用机制。方法50只雄性SD大鼠随机分为空白组,模型组,西药组,人参-玉竹高、低剂量组。慢性不可预见性温和应激(CUMS)方法建立大鼠抑郁模型21 d。西药组大鼠予灌胃盐酸氟西汀,人参-玉竹高、低剂量组大鼠予人参-玉竹提取液,共14 d。旷场实验评估大鼠抑郁行为;HE染色观察大鼠海马细胞形态;酶联免疫吸附试验(ELISA)检测大鼠海马DA、5-HT含量;PCR法检测大鼠海马组织ICAM-1 mRNA水平;免疫组化法测大鼠海马组织NF-κB、MCP-1蛋白表达水平;蛋白免疫印迹法(WB)检测大鼠海马组织PI3K蛋白相对表达。结果给药14 d后,与模型组相比,人参-玉竹药对组大鼠总移动距离和移动平均速度显著升高,海马区DA、5-HT含量水平上调,PI3K蛋白相对表达量显著升高,NF-κB、MCP-1蛋白表达显著降低,ICAM-1水平下降,人参-玉竹药对组对以上指标均有改善作用。结论人参-玉竹药对可改善CUMS大鼠抑郁行为及伴发认知障碍,其发挥抗抑郁作用的机制可能与调控海马区促炎因子的释放及表达有关。

Objective This study aimed to investigate the mechanisms by which a combination of Ginseng and Polygonatum(GP)im⁃proves cognitive impairment associated with depression by analyzing its effects on PI3K,ICAM-1,and MCP-1 expression in the hippo⁃campus of depressive rats.Methods Fifty male SD rats were randomly divided into blank control,model,Western medicine,high-dose GP,and low-dose GP groups.A rat model of depression was established using chronic unpredictable mild stress(CUMS)for 21 days.Rats in the Western medicine group were orally administered fluoxetine hydrochloride,while rats in the high-dose and low-dose GP groups received GP extract for 14 days.Open field test was used to assess depressive behavior,HE staining was employed to observe hip⁃pocampal cell morphology,enzyme-linked immunosorbent assay(ELISA)was conducted to measure hippocampal levels of DA and 5-HT,PCR was used to measure ICAM-1 mRNA levels in the hippocampus,immunohistochemistry was performed to measure NF-κB and MCP-1 protein expression levels,and Western blot(WB)was conducted to measure relative expression of PI3K protein in the hip⁃pocampus.Results After 14 days of treatment,compared with the model group,rats treated with GP showed significantly increased total distance moved and average speed in the open field test.Levels of DA and 5-HT in the hippocampus were elevated,relative expression of PI3K protein was significantly increased,protein expression levels of NF-κB and MCP-1 were significantly decreased,and ICAM-1 levels were reduced.GP treatment improved all these indicators in the treated groups compared to the model group.Conclusion GP treatment can improve depressive behavior and associated cognitive impairment in CUMS rats.The antidepressant effects of GP may be re⁃lated to its regulation of hippocampal pro-inflammatory cytokine release and expression.