白藜芦醇对抑郁模型小鼠认知功能及小清蛋白的影响

Effects of resveratrol on cognitive dysfunction and the expression of parvalbumin in depression model mice

目的探讨白藜芦醇拮抗抑郁症伴发的认知功能障碍及其可能的机制。方法32只C57BL／6J小鼠随机分为四组（n=8）：对照组（Contr01）、模型组（Model）、白藜芦醇给药组（Model＋RSV）、烟酰胺＋白藜芦醇给药组（Model＋NA＋RSV）。除对照组外，其余3组小鼠腹腔注射皮质酮[（20mg／（kg·d）]21d诱导抑郁动物模型，从第22天开始分别给予生理盐水、白藜芦醇[（400mg／（kg·d）]或烟酰胺[（100mg／（kg·d）]及白藜芦醇[（400mg／（kg·d）]21d，通过糖水偏爱实验、新物体识别实验、新位置识别实验及水迷宫实验评价白藜芦醇对抑郁症伴发的认知功能障碍的影响，Western blot检测小鼠海马组织沉默信息调节因子1（silence information regulation factor 1，SIRT1）、过氧化物酶体增殖物激活受体γ辅激活子1α（peroxisome proliferator-activated receptorγ coactivator-1α，PGC-1α）、小清蛋白（parvalbumin，PV）表达，RT—PCR检测小鼠海马SIRT1、PGC-1α及PV的转录水平。结果糖水偏爱实验结果表明皮质酮注射诱导抑郁模型建立成功[F（1.30）=6，P=0．038]。与抑郁模型组相比，白藜芦醇显著增加了新位置识别实验中小鼠识别新位置的次数比[（-0．20±0．37）；（0．16±0．29）]、时间比[（0．10±0．45）；（0．62±0．29）]，降低了距离比[（0．09±0．36）；（0．55±0．27）]；白藜芦醇降低了水迷宫实验中小鼠找到平台的时间[（41±9）s；（26±8）s]、距离[（295±70）cm，（224±43）cm]，该表观有效性伴随着小鼠海马组织SIRT1[F（3．29）=15．60，P〈0．01]，PGC—1±[F（3.29）：7．51，P=0．0006]及PV[（3.29）=17．87，P=0．0004]蛋白表达的增加。而预先给予烟酰胺再给予白藜芦醇，将无法纠正抑郁症伴发的认知功能损伤及SIRT1、PGC—1±、PV表达转录及翻译水平的下调。结论白藜芦醇能够改善抑郁模型小鼠认知功能的损伤，这可能是通过活化SIRT1／PGC—1±信号通路进而增加PV的转录和表达而实现的。

Objective To examine the antidepressant effects of resveratrol （RSV）, and its possible mechanism specialized on improving cognitive function. Methods Thirty-two C57BL/6J mice were randomly divided into four groups：Control, Model, Model＋RSV and Model＋NA＋RSV groups.The mice were subjec-ted eorticosterone （20 mg/（ kg · d）） intraperitoneal injection for 21 consecutive days except the control mice.From the 22nd to 42nd day,the mice in different groups received further treatment with vehicle/ RSV （400 mg/（kg · d） ,op）/NA （100 mg/（kg · d） ,ip）＋RSV （400 mg/（kg · d） ,op） .The sugar preference test, novel object recognition test, novel location recognition test and water maze test were applied to evaluate the cognitive effects of RSV on mice.Subsequently, the silence information regulation factor 1 （SIRT1） ,peroxisome proliferator-activated receptor-γ eoactivator- 1α （ PGC- 1 α ）, parvalbumin （PV） transcription and translation level were evaluated by RT-PCR and Western blotting. Results The sugar preference test showed that the depression model mediated by CORT injection was successfully established（F（1,30） = 6,P= 0.038）. In in the novel object learning test, resveratrol significantly increased the proration on the frequency（ （-0.20± 0.37） vs （0.16±0.29） ）and duration（（0.10±0.45） vs （0.62±0.29） ） and decreased the proration on the distance（（0.09±0.36） vs （0.55±0.27））. In the water maze test,resveratrol reduced the time（（41±9） s; （26± 8 ）s ） and distance （ （295± 70）cm;（ 224±43 ）era）to find the platform.All the results were accompanied with the increased expression of protein SIRT1 （ F （3.29） = 15.60, P〈 0.01 ）, PGC - 1α （ F （3.29） = 7.51, P = 0.0006） and PV （F（3.29） = 17.87,P= 0.0004）. While pretreatment with nicotinamide, resveratrol could not rescue the cognitive impairment and could not reverse the ieereased expression level of protein SIRTI, PGC- 1α and PV.Conelusion Resveratrol can reverse the cognitive dysfunction of depressant mice, which may be achieved by activating the SIRT1/PGC-1α signaling pathway and increasing the transcription and protein expression of PV.