摘要
目的:探讨硫酸茯苓多糖(SP)是否通过调节AMPA受体GluR1的表达而生产抗抑郁作用。方法:实验设假手术组、抑郁症模型组、SP(25、50、100 mg/kg)三个给药组及SP(100 mg/kg)+AMPA受体抑制剂GYKI 52466组,每组动物12只。抑郁症动物模型采用卵巢摘除加慢性不可预知性温和应激(CUMS)法制备。连续灌胃和(或)腹腔注射给药21天。糖水消耗、强迫游泳及敞箱试验观察动物行为变化。海马神经元病理变化采用尼氏染色法检测。GluR1、p-GluR1、CREB、p-CREB和BDNF的蛋白表达采用免疫组化和(或)Western Blot法检测。结果:与模型组相比,SP各组大鼠强迫游泳不动时间(FSIT)明显降低而自发活动(SA)明显增加、糖水摄入量(SC)及糖水偏爱百分比(PSC)明显升高(P<0.05或P<0.01)、海马神经元损伤显著减轻、GluR1和GluR1磷酸化水平及p-CREB、BDNF的表达均明显升高。但与SP(100 mg/kg)剂量组相比,SP+GYKI 52466剂量组大鼠FSIT又明显增加而SA又明显减少,SC及PSC又明显降低,海马GluR1、p-GluR1及p-CREB、BDNF的表达又明显降低(P<0.01)。结论:SP可能通过上调海马GluR1受体的表达,增强GluR1受体功能,促使CREB磷酸化水平升高而上调BDNF的蛋白表达而产生抗抑郁作用。
Objective: The present study investigated whether the antidepressant effects of sulfated pachymaran(SP) were related to changes in the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) receptor subunits in the rat hypothalamus. Methods: A total of 60 SD rats were randomly divided into sham operation group, model group, SP(25, 50, 100 mg/kg) groups and SP(100 mg/kg) plus GYKI 52466(3 mg/kg) group. The rat depression model was established by chronic unpredictable mild stress and ovariectomy. Animals for drugs treatment received daily drug via i.p. and(or) gavage. injection for 21 days. Forced swimming test, open field test and sucrose preference test were used to evaluate the antidepressant effects of SP. Histological changes of hippocampal neurons with Nissl’s staining was recorded. The protein expression was measured by immunohistochemistry and(or) Western blot. Results: SP treatment for 21 day obviously reversed depression-like behavior and hippocampus neuron impairment and markedly increased the spontaneous activity(SA), sucrose consumption(SC) and percentage of SC and significantly attenuated forced swimming immobility time(FSIT),and SP also significantly increased GluR1, p-GluR1, CREB, p-CREB and BDNF protein levels in hippocampus of stress exposed rats(P<0.05 or P<0.01). But the FSIT was significantly increased and the SA, SC and percentage of SC were markedly reduced, and the expression of GluR1, p-GluR1, CREB, p-CREB and BDNF in hippocampal were also obviously decreased in SP plus GYKI 52466 group compared with the SP(100 mg/kg) group(P<0.01). Conclusion: This study demonstrates that sulfated pachymaran produces the antidepressant-like effects in rats, which may be mediated by enhancing GluR1 receptor function and up-regulating the protein expression of p-CREB and BDNF in the hippocampus.
作者
张建英
汤娟
张倩
王雪晴
李先伟
ZHANG Jian-ying;TANG Juan;ZHANG Qin;WANG Xue-qing;LI Xian-wei(School of Medical Image,Wannan Medical College,Wuhu 241002,China;Department of Pharmacology,Wannan Medical College,Wuhu 241002,China)
出处
《中国临床心理学杂志》
CSSCI
CSCD
北大核心
2019年第6期1086-1091,共6页
Chinese Journal of Clinical Psychology
基金
安徽高校省级人文社会科学重点研究项目(SK2014A410)
安徽省高校优秀青年人才支持计划重点项目(gxyqZD2016170)
安徽省高校自然科学研究重点项目(2018A0254)
