探究人参总皂苷联合氟西汀在心肌梗死大鼠合并抑郁模型中的治疗效果

摘要

目的 探讨人参总皂苷(GFS)联合五羟色胺再摄取抑制剂(SSRIs)氟西汀使用对心肌梗死(MI)合并抑郁模型大鼠的治疗效果.方法 SD大鼠左侧开胸永久性结扎左心耳下1～2 mm处冠状动脉左前降支或回旋支制作MI模型;慢性不可控温和应激方法制作抑郁模型. SD大鼠随机均分为对照组、心肌梗死后抑郁组(MI+D组)(2 mL生理盐水灌胃)、氟西汀组(F组)(0.2% 氟西汀按10 mg/kg灌胃)和人参总皂苷+氟西汀组(GFS+ F组)(人参总皂苷按20 mL/kg灌胃+0. 2% 氟西汀按10 mg/kg灌胃) ,每组15只.干预28 d后分别评估大鼠抑郁状态、生存率、心功能、心电生理指标和心肌组织学改变.结果 与对照组比较,M I+D组大鼠的糖水消耗量明显下降,且攀爬次数、爬行距离和爬行速度明显低于对照组;氟西汀与GFS+氟西汀都能明显增加糖水消耗量,增加攀爬次数及爬行距离,GSF+氟西汀的治疗效果优于氟西汀,且GSF+氟西汀同时可提高模型鼠的爬行速度. MI+D组、F组和GFS+F组大鼠之间生存率差异没有统计学意义(P＝ 0.24).与对照组比较,MI+ D组显著增加左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD) 、左心室壁厚度(LVWT ) ,明显降低左心室射血分数(LVEF) 、缩短分数(FS);氟西汀与GFS+氟西汀明显降低模型鼠的LVEDD并提高LVEF ,GFS+氟西汀的效果优于单独使用氟西汀,且GSF+氟西汀同时可降低 LVESD和LVWT .与对照组比较,MI+D组的心室有效不应期(VERP)、动作电位复极90% 时程(APD90)明显延长,心室颤动阈值(VFT)明显降低;氟西汀与GFS+氟西汀明显提高模型大鼠的VFT ,且GFS+氟西汀的效果优于氟西汀,同时GSF+氟西汀可缩短VERP 、APD90 . MI+D组、F组和GFS+F组之间的心梗面积比差异无统计学意义(P＝0.076);氟西汀干预不能改善心梗区心肌厚度及胶原蛋白含量,但GFS+氟西汀明显改善心梗区心肌厚度并提高心梗区的胶原蛋白含量.结论 氟西汀与GFS联合氟西汀都能改善心肌梗死合并抑郁大鼠的抑郁状态、心功能和电生理指标,但GFS联合氟西汀的治疗效果优于单独使用氟西汀,同时GFS联合氟西汀对心肌梗死区心肌厚度和胶原蛋白表达等心脏重构指标也有改善作用.%Objective To investigate the therapeutic effect of total saponins of ginseng (GFS)combined with serotonin re-uptake inhibitor(SSRIs)fluoxetine on rats with myocardial infarction(MI)and depression.Methods Left thoracotomy and per-manent ligation of left atrial appendage were performed to establish MI model in SD rats ,and depression model was established by chronic uncontrollable mild stress.SD rats were randomly divided into control group ,MI depression group(MI+ D group) (intragastric perfusion with 2 mL saline) ,fluoxetine group(F group)(intragastric perfusion with 0.2% fluoxetine at 10 mL/kg) and ginseng fruit saponins+ fluoxetine group(GFS+ F group)(intragastric perfusion of 20 mL/kg ginsenoside + 10 mL/kg 0.2% fluoxetine). The depression degree ,survival rate ,cardiac function ,electrophysiological parameters and histological chan-ges were evaluated after 28 days of intervention.Results Compared with the control group ,the consumption of sugar water in MI+D group was significantly decreased ,and the frequency of climbing ,crawling distance and crawling speed were significantly lower than those of the control group.GFS+fluoxetine and fluoxetine significantly increased the consumption of sugar water , increased the frequency of climbing and crawling distance ,but the treatment of GFS+fluoxetine was better than fluoxetine ,and could also improve the crawl speed. There was no significant difference in survival rate between MI +D group ,F group and GFS+F group(P＝0.24).Compared with the control group ,LVEDD ,LVESD and LVWT were significantly increased ,LVEF and FS significantly reduced in the MI+D group.GFS+fluoxetine and fluoxetine significantly reduced LVEDD in MI+D group and increased LVEF ,but GFS+ fluoxetine was superior to fluoxetine ,and also decreased LVESD and LVWT.Compared with the control group ,VERP and APD90 in MI+D group were significantly prolonged and VFT was significantly decreased.GFS+flu-oxetine and fluoxetine significantly improved the VFT of MI+D rats ,and the effect of GFS+fluoxetine was better than that of fluoxetine ,and they could shorten VERP and APD90 in model group. There was no significant difference in myocardial infarct size between MI+ D group ,F group and GFS+ F group(P＝ 0.076).Fluoxetine intervention did not improve the myocardial thickness and collagen content in the myocardial infarction area ,but GFS+ fluoxetine did.Conclusion Fluoxetine and GFS+fluoxetine can improve depression ,cardiac function and electrophysiological parameters of the rats with MI and depression ,but the effect of GFS+fluoxetine is better than that of fluoxetine ,and the myocardial thickness and collagen expression also have been improved by GFS+fluoxetine.