逍遥散对慢性温和不可预知应激诱导抑郁模型大鼠盲肠炎症应答相关基因表达的影响  

Effect of Xiaoyao powder on caecum inflammatory response related genes expression in chronic unpredictable mild stress model rats

作　　者：陈建丽[1] 孙海峰[2] 秦雪梅[1] 田俊生[1] 

机构地区：[1]山西大学中医药现代研究中心,太原山西030006 [2]山西大学化学化工学院,太原山西030006

出　　处：《中国药理学与毒理学杂志》2015年第4期552-558,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(81173366);国家自然科学基金资助项目(81102833);国家自然科学基金资助项目(81441096);山西省基础研究项目(2012021031-2)~~

摘　　要：目的探讨逍遥散对慢性温和不可预知应激(CUMS)诱导的抑郁大鼠盲肠炎症应答相关基因表达的影响。方法采用孤养并结合10种刺激因子连续21 d复制CUMS模型,造模后恢复7 d,并且同时ig给予氟西汀6.0 mg·kg-1和逍遥散生药46.2 g·kg-1,连续给药28 d。分别于第0,21和28天进行体质量、糖水偏爱及旷场实验检测;第29天采集盲肠组织,计算盲肠指数;采用HE染色观察盲肠组织病理变化;采用反转录聚合酶链式反应(RT-PCR)检测炎症应答相关基因蛋白激活酶受体2(Par2)、Par4和Toll样受体2(Tlr2)转录水平。结果与正常组相比,造模结束及恢复1周后,CUMS模型组大鼠体质量、糖水偏爱率、爬行格数、站立次数和理毛时间显著降低(P<0.05);给予逍遥散生药46.2 g·kg-1或氟西汀6.0 mg·kg-1可显著改善上述抑郁行为。与正常对照组相比,CUMS模型组大鼠盲肠指数显著增加28.6%,而逍遥散治疗后显著降低35.0%(P<0.05)。HE染色结果显示,CUMS模型组大鼠盲肠组织固有结构受损并出现水肿现象,而逍遥散治疗后恢复了盲肠组织固有结构。RT-PCR结果显示,与正常对照组相比,CUMS模型组炎症应答相关的基因Par2,Par4和Tlr2转录水平分别上调138.0%,14.7%和14.5%,Par2具有显著性差异(P<0.01);而逍遥散治疗后分别回调了41.0%,37.9%和67.4%。结论 CUMS激活了大鼠盲肠炎症应答相关基因的表达,而逍遥散可通过降低大鼠盲肠Par2,Par4和Tlr2 m RNA表达而发挥抗抑郁作用。OBJECTIVE To elucidate the effect of chronic unpredictable mild stress （CUMS） and Xiaoyao powder on caecum inflammatory response related genes expression. METHODS To induce the CUMS model, the rats were subjected to separation and 10 different stressors for 21 d and recovered for 7 d. Xiaoyao powder 46.2 g·kg^-1 and fluoxetine 6.0 mg· kg^-1 were administered orally for 28 d. Body mass measurement, sucrose preference test, and open field test were conducted to evalu- ate the changes in behavior on d 0, d 21 and d 28. The caecum samples were collected and the cae- cum index was calculated on d 29. Hematoxylin and eosin stain of different treated groups was used to evaluate the changes in caecum histology, and the reverse transcription-polymerase chain reaction （~RT-PCR） was employed to evaluate the transcriptional levels in related inflammation response genes including proteinase activated receptor 2 ~Par2）, Par4 and Toll-like receptor 2 （T/r2）. RESULTS The body mass, sucrose preference, number of crawlings, number of standings and grooming time of CUMS rats were significantly decreased on d 21 and d 28（P〈0.05）, while administration of fluoxetine and Xiaoyao powder reversed those depressive behaviors. Compared with normal control group, the rat caecum index of CUMS model group was increased by 28.6%, which could be significantly decreased by Xiaoyao powder （P〈0.05）. HE stain showed that the injured inherent structure and edema of caecum appeared in CUMS model rats, and that Xiaoyao powder could improve these symptoms. RT-PCR result showed the transcriptional levels of Par2, Par4 and T/r2 in CUMS rat caecum were increased by 138.0%, 14.7% and 14.5% respectively compared with normal control group, while Xiaoyao powder reversed these changes. CONCLUSION CUMS activates the rat caecum inflammatory response related genes expression while Xiaoyao powder can decrease the levels of Par2, Par4 and T/r2 mRNA expression and have an antidepressant effect.

关 键 词：抑郁症 逍遥散 盲肠 炎症 

分 类 号：R285.5[医药卫生—中药学]