苦杏仁苷通过抑制JNK信号通路改善卒中后抑郁

Amygdalin ameliorates post-stroke depression by inhibiting JNK signal pathway

目的研究苦杏仁苷通过抑制JNK信号通路对卒中后抑郁的改善作用。方法将56只健康SD大鼠随机分为假手术组(n=8)、造模1组(n=8)、造模2组(n=40),造模1组大鼠制备卒中模型,造模2组大鼠制备卒中后抑郁模型。造模成功后,卒中后抑郁模型大鼠随机分为卒中+抑郁组、卒中+抑郁+苦杏仁苷低剂量组(40 mg·kg^(-1))、卒中+抑郁+苦杏仁苷中剂量组(80 mg·kg^(-1))、卒中+抑郁+苦杏仁苷高剂量组(120 mg·kg^(-1))、卒中+抑郁+氟西汀组(1.8 mg·kg^(-1))。随后按相应剂量给药,连续给药30 d。观察大鼠Zea Longa评分,测定蔗糖水消耗量;H&E染色观察海马组织病理变化;TUNEL染色观察海马组织神经元细胞凋亡;透射电镜观察海马组织超微结构变化;Western blot检测海马组织PSD95、SYN、BDNF及JNK、p-JNK、c-Jun、p-c-Jun、cleaved-caspase 3、Bcl-2蛋白表达。结果与假手术组比较,卒中组、卒中+抑郁组大鼠Zea Longa神经行为学评分,细胞凋亡百分率,以及海马组织p-JNK、c-Jun、p-c-Jun、cleaved-caspase 3蛋白表达明显升高(P<0.05);蔗糖水消耗量,海马组织PSD95、SYN、BDNF、Bcl-2蛋白表达明显降低(P<0.05)。与卒中+抑郁组比较,卒中+抑郁+苦杏仁苷低剂量组、卒中+抑郁+苦杏仁苷中剂量组、卒中+抑郁+苦杏仁苷高剂量组、卒中+抑郁+氟西汀组大鼠Zea Longa神经行为学评分,细胞凋亡百分率,以及海马组织p-JNK、c-Jun、p-c-Jun、cleaved-caspase 3蛋白表达明显降低(P<0.05),蔗糖水消耗量、海马组织PSD95、SYN、BDNF、Bcl-2蛋白表达明显升高(P<0.05)。与卒中+抑郁+氟西汀组比较,卒中+抑郁+苦杏仁苷高剂量组大鼠Zea Longa神经行为学评分,细胞凋亡百分率,以及海马组织p-JNK、c-Jun、p-c-Jun、cleaved-caspase 3蛋白表达明显降低(P<0.05),海马组织PSD95、SYN、BDNF、Bcl-2蛋白表达明显升高(P<0.05)。结论苦杏仁苷改善卒中后抑郁样行为,可能与抑制海马JNK信号通路有关。

Objective To study the ameliorative effect of amygdalin on post-stroke depression by inhibiting JNK signal pathway.Methods A total of 30 healthy SD rats were randomly divided into sham operation group(n=8),model group 1(n=8)and model group 2(n=40).Stroke models were made in group 1,and post-stroke depression models were made in group 2.After successful modeling,the post-stroke depression model rats were randomly divided into stroke+depression group,stroke+depression+amygdalin low dose group(40 mg·kg^(-1)),stroke+depression+amygdalin medium dose group(80 mg·kg^(-1)),stroke+depression+amygdalin high dose group(120 mg·kg^(-1)),and stroke+depression+fluoxetine group(1.8 mg·kg^(-1)).Then the drug was given according to the corresponding dose for 30 days.The Zea Longa score and sucrose water consumption were observed;the pathological changes of hippocampal tissue were observed by H&E staining;the neuronal apoptosis was observed by TUNEL staining;the ultrastructural changes of hippocampal tissue were observed by transmission electron microscope,and Western blot was used to detect the expression of PSD95,SYN,BDNF and JNK,p-JNK,c-Jun,p-c-Jun,cleaved-caspase 3 and Bcl-2 protein in hippocampal tissue.Results Compared with the sham operation group,the Zea Longa neurobehavioral score,the percentage of apoptosis and the expression of p-JNK,c-Jun and p-c-Jun protein in hippocampus were significantly increased,while the sucrose water consumption,PSD95,SYN,BDNF and Bcl-2 protein expressions in hippocampus were significantly decreased in stroke group and stroke+depression group(P<0.05).Compared with the stroke+depression group,Zea Longa neurobehavioral scores,apoptosis percentage and hippocampal tissue p-JNK,c-Jun,p-c-Jun,cleaved-caspase 3 protein expression was significantly decreased(P<0.05),and sucrose water consumption,hippocampal tissue PSD95,SYN,BDNF,and Bcl-2 protein expression were significantly increased in stroke+depression+amygdalin low dose group,stroke+depression+amygdalin medium dose group,stroke+depression+amygdalin high dose group,and stroke+depression+fluoxetine group(P<0.05).Compared with the stroke+depression+fluoxetine group,Zea Longa neurobehavioral score,apoptosis percentage and hippocampal tissue p-JNK,c-Jun,p-c-Jun,cleaved-caspase 3 protein expression were significantly decreased(P<0.05),and hippocampal tissue PSD95,SYN,BDNF,and Bcl-2 protein expressions were significantly increased in the stroke+depression+amygdalin high-dose group(P<0.05).Conclusion Amygdalin improves depression-like behavior after stroke,which may be related to the inhibition of hippocampal JNK signal pathway.