目的 从肠道菌群角度探讨姜黄素(CUR)对间歇性睡眠剥夺大鼠产生抗抑郁样作用的可能机制。方法 Wistar大鼠随机分为对照组、大平台对照组(BP)、模型组和CUR(70 mg/kg)组,采用改良的平台水环境法建立大鼠间歇性睡眠剥夺模型;通过敞箱实验和糖水偏好实验考察大鼠的抑郁样行为;同时收集粪便样本,提取肠道菌群的DNA,应用细菌16S rRNA基因序列设计引物,进行荧光定量PCR(qRT-PCR)检测。结果 行为学实验结果表明模型大鼠出现抑郁样行为,敞箱实验得分和糖水偏好率显著低于BP组(P<0.01),给予CUR可显著改善抑郁样行为;qRT-PCR检测表明,模型组粪便中的大肠杆菌、拟杆菌及有益菌双歧杆菌和乳酸杆菌,与对照组比较显著减少,有害菌产气荚膜梭菌相对量显著增加(P<0.05、0.01)。CUR组大鼠肠道菌群总量增加,除产气荚膜梭菌显著减少外,其余几种细菌相对量较模型组显著增加(P<0.05、0.01)。结论 间歇性睡眠剥夺引起大鼠抑郁样状态和肠道菌群失调,CUR改善肠道菌群失调,可能为其改善抑郁样状态的机制之一。

Objective To study the effects of curcumin(CUR) on gut microbiota of interval sleep deprivation(ISD) rats.Methods Wistar rats were randomly divided into control group, big platform(BP) control group, model group, and CUR(70 mg/kg) group.Firstly, ISD model rats were established by improved small platform method;Then, open field test and sucrose preference test were utilized to assess the depression-like behavior of the ISD model rats and intervention effects of CUR;Thirdly, gut microbiota DNA samples were extracted from feces, the primers of Escherichia coli, Bifidobacterium, Lactobacillus, Clostridium perfringens, and Bacteroides were designed by 16S rRNA gene sequence, and the fluprescence qualitation of the bacteria through general PCR was obtained.Results The results of behavioral experiments showed that open field test scores and sucrose preference rate were significantly lower than those of the BP group(P<0.01), and CUR played a significant improving role.The qRT-PCR data suggested that the relative expression of E.coli, Bifidobacterium, Lactobacillus, and Bacteroides of ISD model rats were lower than those in normal and big platform groups in ISD model rats, while higher for Clostridium perfringens(P<0.05, 0.01).The amounts of E.coli, Bifidobacterium, Lactobacillus, and Bacteroides of CUR intervened group were higher than those in ISD model rats, except for Clostridium perfringens(P<0.05, 0.01).Conclusion The results show that as a stress, ISD not only causes mental disorders in rats, but also leads to the changes of five bacteria strains.CUR could alter the imbalance of gut microbiota, which might be one of the mechanisms of its effects on depression-like behaviors of ISD rats.

上海中医药大学预算内项目资助(2013JW17);上海中医药大学中药学一流学科创新研究基金资助(ZYX-CXYJ-018);"085"一流学科建设科技创新支撑计划(引导创新计划:085ZY1205);上海高校特聘教授(东方学者)岗位计划资助(2011-50)