【摘要】 目的:探讨乌灵胶囊对慢性不可预见性温和应激(chronic unpredictable mild stress , CMS)抑郁模型大鼠海马齿状回脑源性神经营养因子(brain-derived neurotrophic factor , BDNF)、神经再生,以及连接蛋白43(connexin 43 ,Cx43)表达的影响。方法:45只成年雄性Sprague-Dawley大鼠随机分入对照组(n=15)、模型组(n=15)和乌灵胶囊组(n=15)。模型组和乌灵胶囊组大鼠接受连续3周的CMS,造模期间,乌灵胶囊按100 mg/(kg.d)加入乌灵胶囊组大鼠的膳食中,连续治疗21 d。采用糖水偏爱实验评价大鼠的抑郁程度。抑郁行为测试结束后,取双侧海马组织,用免疫组织化学法检测BDNF与5-溴脱氧尿苷(5-bromodeoxyuridine ,BrdU)的表达;用逆转录聚合酶链反应和蛋白印迹法检测海马中Cx43 mRNA与蛋白表达。结果:慢性应激大鼠齿状回BDNF阳性表达、新生细胞数及Cx43 mRNA和蛋白表达水平均较正常大鼠明显下降。乌灵胶囊治疗后,CMS大鼠抑郁行为得到改善,异常的海马神经再生恢复,Cx43 mRNA和蛋白表达变得正常,但BDNF表达无明显改变。结论:乌灵胶囊可增加CMS模型大鼠海马神经再生及改善抑郁症状,其机制可能与增加Cx43表达有关,与BDNF无关。更多还原

【Abstract】 Objective:To investigate the effects of Wuling Capsule,a compound traditional Chinese herbal medicine,on hippocampal neurogenesis by examining the expressions of brain-derived neurotrophic factor (BDNF) and connexin 43 (Cx43) in rats with depression induced by chronic unpredictable mild stress (CMS),and thereby to explore its antidepressant mechanism.Methods:Forty-five adult male Sprague-Dawley rats were randomly divided into three groups:control group (n=15),untreated group (n=15) and Wuling group (n=15).All rats except those in the control group were subjected to 3-week CMS to induce depression.At the same time Wuling Capsule was daily added to the diet of the rats in the Wuling group at a dose of 100 mg/kg body weight for 21 days.The degree of depression was determined by sucrose preference test.BDNF expression and neurogenesis were tested by using immunohistochemical staining with BDNF and 5-bromodeoxyuridine (BrdU) antibodies;and the mRNA and protein expression levels of Cx43 in hippocampus were examined by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting.Results:The numbers of BDNF-positive neurons and BrdU-positive particles in dentate gyrus (DG) were significantly decreased in CMS rats as compared with the normal rats,and the same changes were found in Cx43 mRNA and protein expressions.After Wuling Capsule treatment,the depressed behaviors were improved.Moreover,the reduced expression levels of Cx43 mRNA and protein and fewer newborn neurons induced by CMS were recovered to the normal levels.However,BDNF-positive cells remained low in DG.Conclusion:Wuling Capsule can improve the low hippocampal neurogenesis in rats subjected to CMS and the antidepressant effects are related to enhancing the Cx43 expression but not through BDNF mediation.更多还原