Effect of Albiziae Flos and Polygalae Radix Alone and Their Combination on Depression-like Behavior and CREB and NOX2 Expression in Hippocampus of Chronic Unpredictable Stress-induced Rats

Bing-mei WANG; Pan QIAO; Wei WANG; Wu SONG; Chang LIU; Xing-ye WANG; Ying ZHANG; Da-shi YING; Xi-jun DONG

doi:10.13422/j.cnki.syfjx.20211604

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Effect of Albiziae Flos and Polygalae Radix Alone and Their Combination on Depression-like Behavior and CREB and NOX2 Expression in Hippocampus of Chronic Unpredictable Stress-induced Rats

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- Effect of Albiziae Flos and Polygalae Radix Alone and Their Combination on Depression-like Behavior and CREB and NOX2 Expression in Hippocampus of Chronic Unpredictable Stress-induced Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 17, Pages: 32-39(2021)
- 作者机构：
  
  1.长春中医药大学，长春 130117
  2.吉林农业科技学院，吉林吉林 132101
  3.长春市应氏中医门诊部，长春 130022
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211604
  CLC： R2-0;R22;R285.5;R33
- Received：23 April 2021，
  
  Published Online：02 July 2021，
  
  Published：05 September 2021
- 稿件说明：
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王冰梅,乔盼,王微等.合欢花-远志单味药及药对对慢性不可预知应激大鼠抑郁样行为及海马CREB，NOX2表达的影响[J].中国实验方剂学杂志,2021,27(17):32-39.

WANG Bing-mei,QIAO Pan,WANG Wei,et al.Effect of Albiziae Flos and Polygalae Radix Alone and Their Combination on Depression-like Behavior and CREB and NOX2 Expression in Hippocampus of Chronic Unpredictable Stress-induced Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(17):32-39.
王冰梅,乔盼,王微等.合欢花-远志单味药及药对对慢性不可预知应激大鼠抑郁样行为及海马CREB，NOX2表达的影响[J].中国实验方剂学杂志,2021,27(17):32-39. DOI： 10.13422/j.cnki.syfjx.20211604.

WANG Bing-mei,QIAO Pan,WANG Wei,et al.Effect of Albiziae Flos and Polygalae Radix Alone and Their Combination on Depression-like Behavior and CREB and NOX2 Expression in Hippocampus of Chronic Unpredictable Stress-induced Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(17):32-39. DOI： 10.13422/j.cnki.syfjx.20211604.

摘要

目的

观察合欢花-远志单味药及药对改善慢性不可预知应激大鼠抑郁样行为的作用，并通过海马组织超微结构及环腺苷酸反应元件结合蛋白（CREB），烟酰胺腺嘌呤二核苷酸磷酸氧化酶2（NOX2）表达水平初步研究其机制。

方法

72只Wistar大鼠随机分为正常组、模型组、合欢花组、远志组、合欢花-远志药对组及氟西汀组。除正常组外，其余5组均采用慢性不可预知应激刺激与孤养相结合的方法制备抑郁模型。自造模第1天起，合欢花组、远志组和药对组分别给与总生药量1.05 g·kg

-1

的水煎液，氟西汀组给予2.1 mg·kg

-1

剂量盐酸氟西汀水溶液，正常组和模型组给予蒸馏水，连续灌胃28 d。分别于造模前1 d及造模后第7，14，21，28天进行敞箱实验和强迫游泳实验，第28天电镜观察海马组织形态学改变，紫外分光光度法检测海马组织超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量，实时荧光定量聚合酶链式反应（Real-time PCR）及蛋白免疫印迹法（Western blot）检测CREB和NOX2表达水平。

结果

行为学实验结果显示，与正常组比较，模型组大鼠水平活动次数和糖水消耗量减少，游泳不动时间增加（

0.05，

0.01）；与模型组比较，合欢花组、远志组和药对组大鼠水平活动次数和糖水消耗量明显增加，游泳不动时间明显缩短（

0.05，

0.01）；与单味药比较，药对组各项行为学指标差异有统计学意义（

0.05）。形态学结果发现，模型组海马组织线粒体肿胀明显，超微结构被破坏，而各给药组大鼠海马组织超微结构接近正常。与正常组比较，模型组海马组织SOD活性降低，MDA含量升高（

0.01）；与模型组比较，合欢花组、远志组和药对组大鼠海马组织SOD活性升高，而MDA含量降低（

0.05，

0.01）；与单味药比较，药对组差异有统计学意义（

0.05，

0.01）。Real-time PCR和Western blot结果表明，与正常组比较，模型组大鼠海马组织NOX2表达增加，CREB的表达减少（

0.05，

0.01）；与模型组比较，合欢花组、远志组和药对组大鼠海马组织NOX2表达减少，CREB表达增加（

0.05，

0.01）；与单味药比较，药对组大鼠海马组织NOX2和CREB蛋白表达差异有统计学意义（

0.01）。

结论

合欢花-远志单味药及药对能改善慢性不可预知应激大鼠的抑郁样行为，可能与减少氧化应激和上调CREB表达、下调NOX2表达有关。

Abstract

Objective

To observe the effects of Albiziae Flos （AF） and Polygalae Radix （PR） alone and their combination on the improvement of depression-like behavior in rats with chronic unpredictable stress （CUS） as well as on hippocampal ultrastructure and the expression of cyclic adenosine monophosphate response element binding protein （CREB） and nicotinamide adenine dinucleotide phosphate oxidase 2 （NOX2）， to explore their action mechanisms.

Method

Seventy-two Wistar rats were randomly divided into the normal group， model group， AF group， PR group， AF-PR group， and fluoxetine group. Rats in all groups except for the normal group were exposed to CUS and separated feeding to induce depression. Since the first day of modeling， rats in the AF group， PR group， AF-PR group were provided with the corresponding decoction containing 1.05 g·kg

-1

total crude drug by gavage， the ones in the fluoxetine group with 2.1 mg·kg

-1

fluoxetine hydrochloride aqueous solution， and those in the normal group and model group with the distilled water， for 28 successive days. The open field test and forced swimming test were performed 1 d before modeling and 7， 14， 21， 28 d after modeling， respectively. The morphological changes in hippocampus were observed under an electron microscope on the 28

day. The superoxide dismutase （SOD） and malondialdehyde （MDA） levels in hippocampus were detected by ultraviolet spectrophotometry， and the expression levels of CREB and NOX2 were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot.

Result

The behavioral experiment results showed that the number of horizontal activities and sugar water consumption in the model group declined as compared with those in the normal group， while the immobility time in the forced swimming test was prolonged （

0.05，

0.01）. Compared with the model group， the AF group， PR group， and AF-PR group exhibited elevated number of horizontal activities， increased sugar water consumption but shortened immobility time in the forced swimming test （

0.05，

0.01）. Compared with the AF group or PR group， the AF-PR group showed significantly different behavioral indexes （

0.05）. Morphological results showed that the mitochondria of the model group were obviously swollen and the ultrastructure of the hippocampus was destroyed. By contrast， the hippocampal ultrastructure in each administration group was close to normal. The comparison with the normal group revealed that the activity of SOD in the hippocampus of the model group was significantly reduced， whereas the content of MDA was elevated （

0.01）. Compared with the model group， the AF group， PR group， and AF-PR group displayed increased activity of SOD and decreased content of MDA in the hippocampal tissues （

0.05，

0.01）. Compared with AF or PR alone， the herbal pair AF-PR resulted in significant differences in the above-mentioned indexes （

0.05，

0.01）. The results of Real-time PCR and Western blot demonstrated that NOX2 expression in the hippocampus of the model group was up-regulated in comparison with that in the normal group， while the CREB expression was down-regulated （

0.05，

0.01）. Compared with the model group， the AF group， PR group， and AF-PR group all showed diminished NOX2 expression but elevated CREB expression in the hippocampal tissues （

0.05，

0.01）. The protein expression levels of NOX2 and CREB in the AF group or PR group were significantly different from those in the AF-PR group （

0.01）.

Conclusion

AF and PR alone and their combination improve the depression-like behavior of rats exposed to CUS， which may be related to the reduction of oxidative stress， the up-regulation of CREB expression， and the down-regulation of NOX2 expression in hippocampus.

关键词

Keywords

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