[目的]研究c-Jun氨基端激酶(c-Jun N-terminal protein kinase,JNK)在1-甲基4-苯基-1,2,3,6-四氢吡啶(MPTP)所致小鼠帕金森病(Parkinson's disease,PD)模型中对PD黑质多巴胺(Dopamine,DA)能神经元丢失的可能机制以及人参皂甙Rg1的...[目的]研究c-Jun氨基端激酶(c-Jun N-terminal protein kinase,JNK)在1-甲基4-苯基-1,2,3,6-四氢吡啶(MPTP)所致小鼠帕金森病(Parkinson's disease,PD)模型中对PD黑质多巴胺(Dopamine,DA)能神经元丢失的可能机制以及人参皂甙Rg1的神经保护作用。[方法]采用神经毒素MPTP制备PD小鼠模型,免疫组织化学法与蛋白印迹法观察各组小鼠黑质酪氨酸羟化酶(TH)和磷酸化c-Jun(p-c-jun)表达变化;原位末端标记法(TUNEL)观察黑质细胞凋亡数量变化。[结果]与对照组相比,模型组小鼠黑质致密带TH阳性神经元显著减少约55%(P﹤0.01),p-c-jun表达水平亦明显升高,黑质神经元TUNEL阳性细胞数量增高;人参皂甙Rg1干预组黑质TH阳性神经元细胞丢失明显减轻31%(P﹤0.01),p-c-jun表达水平明显下降,黑质神经元TUNEL阳性细胞数量显著减少。[结论]JNK通路可能通过凋亡途径参与模型小鼠黑质多巴胺能神经元丢失过程;人参皂甙Rg1可在一定程度上阻抑黑质区JNK信号通路,减轻MPTP诱导的PD小鼠黑质DA能神经元凋亡;人参皂甙Rg1对帕金森病小鼠具有一定的神经保护作用。展开更多
Objective: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids(CONR) on myocardial apoptosis of diabetic atherosclerosis(DA) rabbits Method...Objective: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids(CONR) on myocardial apoptosis of diabetic atherosclerosis(DA) rabbits Methods: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group(450 mg/kg), CONR medium-dose group(150 mg/kg), CONR low-dose group(50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose(FBG), glycosylated hemoglobin(GHB), glycosylated serum protein(GSP), fructoseamine(FRA), aldose reductase(AR), advanced glycation end products(AGEs) in serum were measured by enzyme linked immunosorbent assay(ELISA) method;the expression of receptor of AGEs(RAGE) in myocardial tissue were observed by immunohistochemical method;and p-Jun N-terminal kinase(p-JNK), caspase-3, B-cell lymphoma-2(bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by Td T-mediated d UTPnick-end labeling(TUNEL) method, and apoptosis index(AI) was calculated. Results: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index(AI) were significantly increased and bcl-2 protein was significantly decreased in the model group(P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high-and medium-dose groups(P<0.01). FBG and GHB showed a significant decline in CONR low-dose group(P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups(P<0.01);high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups(P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group(P<0.01);middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group(P<0.01). Conclusion: CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.展开更多
文摘[目的]研究c-Jun氨基端激酶(c-Jun N-terminal protein kinase,JNK)在1-甲基4-苯基-1,2,3,6-四氢吡啶(MPTP)所致小鼠帕金森病(Parkinson's disease,PD)模型中对PD黑质多巴胺(Dopamine,DA)能神经元丢失的可能机制以及人参皂甙Rg1的神经保护作用。[方法]采用神经毒素MPTP制备PD小鼠模型,免疫组织化学法与蛋白印迹法观察各组小鼠黑质酪氨酸羟化酶(TH)和磷酸化c-Jun(p-c-jun)表达变化;原位末端标记法(TUNEL)观察黑质细胞凋亡数量变化。[结果]与对照组相比,模型组小鼠黑质致密带TH阳性神经元显著减少约55%(P﹤0.01),p-c-jun表达水平亦明显升高,黑质神经元TUNEL阳性细胞数量增高;人参皂甙Rg1干预组黑质TH阳性神经元细胞丢失明显减轻31%(P﹤0.01),p-c-jun表达水平明显下降,黑质神经元TUNEL阳性细胞数量显著减少。[结论]JNK通路可能通过凋亡途径参与模型小鼠黑质多巴胺能神经元丢失过程;人参皂甙Rg1可在一定程度上阻抑黑质区JNK信号通路,减轻MPTP诱导的PD小鼠黑质DA能神经元凋亡;人参皂甙Rg1对帕金森病小鼠具有一定的神经保护作用。
基金Supported by National Natural Science Foundation of China(No.81374026)。
文摘Objective: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids(CONR) on myocardial apoptosis of diabetic atherosclerosis(DA) rabbits Methods: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group(450 mg/kg), CONR medium-dose group(150 mg/kg), CONR low-dose group(50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose(FBG), glycosylated hemoglobin(GHB), glycosylated serum protein(GSP), fructoseamine(FRA), aldose reductase(AR), advanced glycation end products(AGEs) in serum were measured by enzyme linked immunosorbent assay(ELISA) method;the expression of receptor of AGEs(RAGE) in myocardial tissue were observed by immunohistochemical method;and p-Jun N-terminal kinase(p-JNK), caspase-3, B-cell lymphoma-2(bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by Td T-mediated d UTPnick-end labeling(TUNEL) method, and apoptosis index(AI) was calculated. Results: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index(AI) were significantly increased and bcl-2 protein was significantly decreased in the model group(P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high-and medium-dose groups(P<0.01). FBG and GHB showed a significant decline in CONR low-dose group(P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups(P<0.01);high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups(P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group(P<0.01);middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group(P<0.01). Conclusion: CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.
