芍药内酯苷和芍药苷对血虚肝郁证大鼠模型的影响及作用机制研究
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摘要
目的:分析白芍"养血柔肝"功效物质基础与作用机制及血虚肝郁证证候实质。方法:选取健康雄性SD大鼠48只,随机数字表法将大鼠分成对照组、模型组、芍药内酯苷组及芍药苷组,每组12只,制备血虚肝郁大鼠模型,造模第1天开始给药,芍药内酯苷组灌胃30 mg/(kg·d)芍药内酯苷,芍药苷组灌胃30 mg/(kg·d)芍药苷,对照组和模型组灌胃等剂量生理盐水,共灌胃3周;观察大鼠一般活动情况,高效液相色谱-电化学检测系统检测大鼠海马内单胺类神经递质5-羟吲哚乙酸(5-hy-droxyindole acetic acid,5-HIAA)、去甲肾上腺素(Norepinephrine,NE)、肾生腺素(Epinephrine,E)、5-羟色胺(5-hydroxytryptamine,5-HT)及多巴胺(Dopaminem,DA)水平,蛋白免疫印迹法检测大鼠海马内脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)、磷酸化元件结合蛋白(P-c AMP-response element binding protein,P-CREB)、环磷酸腺苷(Cydic adenosine monophosp hate,c AMP)及蛋白激酶A (Protein kinase A,PKA)蛋白表达状况。结果:与对照组比较,模型组大鼠5-HIAA、NE、E、5-HT、DA、PKA、BDNF、c AMP、PKA均显著降低,P-CREB显著升高,差异均有统计学意义(P <0.05);与模型组比较,芍药内酯苷组和芍药苷组大鼠5-HIAA、NE、E、5-HT、DA、PKA、BDNF及其大脑皮层内c AMP、PKA水平均升高,P-CREB蛋白显著降低,差异均有统计学意义(P <0.05)。结论:芍药内酯苷和芍药苷可调节血虚肝郁大鼠神经递质含量,调控大鼠机体内c AMP/PKA信号路径内相关蛋白表达,起保护神经作用,它们都是白芍养血柔肝功效物质基础。
Objective:To analyze the material basis and mechanism of white peony root in nourishing blood and softening the liver,and to analyze the essence of the syndrome of blood deficiency and the liver depression syndrome. Methods:Selected 48 healthy male SD rats and divided them into the control group, the model group, the albiflorin group and the paeoniflorin group according to the random number table method,12 rats in each group. Established the rat models with blood deficiency and the liver depression syndrome and started to treat them with medicine from the first day. The albiflorin group was given 30 mg/(kg·d) of albiflorin by gavage, the paeoniflorin group was given 30 mg/(kg·d) of paeoniflorin by gavage,and the control group and the model group was given the same amount of normal saline by gavage. The four groups received treatment for three weeks. Observed the general activity of rats,detected levels of 5-hy-droxyindole acetic acid(5-HIAA),norepinephrine(NE),epinephrine(E),5-hydroxytryptamine(5-HT) and dopaminem(DA)in hippocampus by high performance liquid chromatography electrochemical detection system, and detected the expressions of brain-derived neurotrophic factor(BDNF), P-cAMP-response element binding protein(P-CREB), Cydic adenosine monophosp hate(cAMP) and protein kinase A(PKA) in hippocampus of rats by immunoblotting test. Results:Compared with those in the control group,levels of 5-HIAA,NE,E,5-HT,DA,PKA and BDNF as well as levels of cAMP and PKA in cerebral cortex in the albiflorin group and the paeoniflorin group were lower, while the P-CREB levels were significantly higher, differences being significant(P < 0.05).Compared with those in the model group,levels of 5-HIAA,NE,E,5-HT,DA,PKA and BDNF as well as levels of cAMP and PKA in cerebral cortex in the albiflorin group and the paeoniflorin group were higher, while the P-CREB levels were lower,significantly differences being significant(P < 0.05). Conclusion:Albiflorin and paeoniflorin can regulate the content of neurotransmitter of rats with blood deficiency and the liver depression syndrome,regulate protein expressions in cAMP/PKA signaling pathway of rats and protect the nerves. Albiflorin and paeoniflorin are the material basis of white peony root in nourishing blood and softening the liver.
Objective:To analyze the material basis and mechanism of white peony root in nourishing blood and softening the liver,and to analyze the essence of the syndrome of blood deficiency and the liver depression syndrome. Methods:Selected 48 healthy male SD rats and divided them into the control group, the model group, the albiflorin group and the paeoniflorin group according to the random number table method,12 rats in each group. Established the rat models with blood deficiency and the liver depression syndrome and started to treat them with medicine from the first day. The albiflorin group was given 30 mg/(kg·d) of albiflorin by gavage, the paeoniflorin group was given 30 mg/(kg·d) of paeoniflorin by gavage,and the control group and the model group was given the same amount of normal saline by gavage. The four groups received treatment for three weeks. Observed the general activity of rats,detected levels of 5-hy-droxyindole acetic acid(5-HIAA),norepinephrine(NE),epinephrine(E),5-hydroxytryptamine(5-HT) and dopaminem(DA)in hippocampus by high performance liquid chromatography electrochemical detection system, and detected the expressions of brain-derived neurotrophic factor(BDNF), P-cAMP-response element binding protein(P-CREB), Cydic adenosine monophosp hate(cAMP) and protein kinase A(PKA) in hippocampus of rats by immunoblotting test. Results:Compared with those in the control group,levels of 5-HIAA,NE,E,5-HT,DA,PKA and BDNF as well as levels of cAMP and PKA in cerebral cortex in the albiflorin group and the paeoniflorin group were lower, while the P-CREB levels were significantly higher, differences being significant(P < 0.05).Compared with those in the model group,levels of 5-HIAA,NE,E,5-HT,DA,PKA and BDNF as well as levels of cAMP and PKA in cerebral cortex in the albiflorin group and the paeoniflorin group were higher, while the P-CREB levels were lower,significantly differences being significant(P < 0.05). Conclusion:Albiflorin and paeoniflorin can regulate the content of neurotransmitter of rats with blood deficiency and the liver depression syndrome,regulate protein expressions in cAMP/PKA signaling pathway of rats and protect the nerves. Albiflorin and paeoniflorin are the material basis of white peony root in nourishing blood and softening the liver.
引文
[1]朱映黎,王林元,赵丹萍,等.芍药内酯苷、芍药苷对血虚免疫抑制小鼠的补血作用及机制[J].北京中医药大学学报,2016,39(3):204-207.
[2]Joyner RP,Tang JH,Helenius J,et al.A glucose-starvation response regulates the diffusion of macromolecules[J].Elife,2016,5(2):152-155.
[3]王成龙,王林元,朱映黎,等.芍药内酯苷对放射线辐照法致血虚免疫抑制小鼠的补血作用及机制研究[J].环球中医药,2017,10(7):682-687.
[4]Lin MY,Su YC,Li YZ,et al.Anti-tumor effect of Radix Paeoniae Rubra extract on mice bladder tumors using intravesical therapy[J].Oncology Letters,2016,12(2):904-910.
[5]张建军,李艳霞,王景霞,等.辐照结合束缚应激致血虚肝郁大鼠证候模型的建立[J].中华中医药杂志,2014,29(7):2176-2179.
[6]Boukhenouna S,Mazon H,Branlant G,et al.Evidence that glutathione and the glutathione system efficiently recycle 1-cys sulfiredoxin in vivo[J].Antioxid Redox Signal,2017,22(9):731-743.
[7]王成龙,王林元,王景霞,等.芍药内酯苷、芍药苷对放射线辐照致血虚小鼠IL-3,GM-CSF,IL-6及TNF-α的影响[J].世界中医药,2016,11(8):1574-1577.
[8]Qiu H,Zhang L,Zhu M,et al.Capture of anti-coagulant active ingredients from Moutan Cortex by platelet immobilized chromatography and evaluation of anticoagulant activity in rats[J].Biomedicine Pharmacotherapy,2017,95(25):235-244.
[9]朱映黎,王林元,王成龙,等.芍药内酯苷和芍药苷对慢性束缚应激大鼠神经营养因子以及一氧化氮影响的研究[J].中国中药杂志,2016,41(22):4240-4246.
[10]朱映黎,王林元,王景霞,等.芍药内酯苷对环磷酰胺致血虚小鼠的补血作用及机制[J].中华中医药杂志,2016,31(5):1892-1896.
[11]Xie P,Cui L,Shan Y,et al.Antithrombotic effect and mechanism of radix paeoniae rubra[J].Bio Med Research International,2017,2017:1-9.
[12]李伟,王景霞,葛阳,等.芍药苷对血虚肝郁证模型大鼠海马谷氨酸及其不同类型受体m RNA表达的影响[J].中华中医药杂志,2016,31(4):1241-1244.
[13]王景霞,周恬恬,朱映黎,等.芍药苷对血虚肝郁证大鼠海马CA1区s GCβ1和5种PDE亚型蛋白表达的影响[J].环球中医药,2016,9(7):790-794.
[14]Li X,Shi F,Zhang R,et al.Pharmacokinetics,Safety,and Tolerability of Amygdalin and Paeoniflorin After Single and Multiple Intravenous Infusions of Huoxue-Tongluo Lyophilized Powder for Injection in Healthy Chinese Volunteers[J].Clinical Therapeutics,2016,38(2):327-337.
[15]王成龙,王林元,王景霞,等.芍药内酯苷及芍药苷对慢性束缚应激配合孤养肝郁模型大鼠行为学及下丘脑-垂体-肾上腺轴的影响[J].中华中医药杂志,2017,32(7):3121-3125.
[16]周恬恬,王林元,王景霞,等.芍药苷对血虚肝郁证大鼠海马磷酸二酯酶不同亚型的影响[J].北京中医药大学学报,2016,39(4):288-292.
[2]Joyner RP,Tang JH,Helenius J,et al.A glucose-starvation response regulates the diffusion of macromolecules[J].Elife,2016,5(2):152-155.
[3]王成龙,王林元,朱映黎,等.芍药内酯苷对放射线辐照法致血虚免疫抑制小鼠的补血作用及机制研究[J].环球中医药,2017,10(7):682-687.
[4]Lin MY,Su YC,Li YZ,et al.Anti-tumor effect of Radix Paeoniae Rubra extract on mice bladder tumors using intravesical therapy[J].Oncology Letters,2016,12(2):904-910.
[5]张建军,李艳霞,王景霞,等.辐照结合束缚应激致血虚肝郁大鼠证候模型的建立[J].中华中医药杂志,2014,29(7):2176-2179.
[6]Boukhenouna S,Mazon H,Branlant G,et al.Evidence that glutathione and the glutathione system efficiently recycle 1-cys sulfiredoxin in vivo[J].Antioxid Redox Signal,2017,22(9):731-743.
[7]王成龙,王林元,王景霞,等.芍药内酯苷、芍药苷对放射线辐照致血虚小鼠IL-3,GM-CSF,IL-6及TNF-α的影响[J].世界中医药,2016,11(8):1574-1577.
[8]Qiu H,Zhang L,Zhu M,et al.Capture of anti-coagulant active ingredients from Moutan Cortex by platelet immobilized chromatography and evaluation of anticoagulant activity in rats[J].Biomedicine Pharmacotherapy,2017,95(25):235-244.
[9]朱映黎,王林元,王成龙,等.芍药内酯苷和芍药苷对慢性束缚应激大鼠神经营养因子以及一氧化氮影响的研究[J].中国中药杂志,2016,41(22):4240-4246.
[10]朱映黎,王林元,王景霞,等.芍药内酯苷对环磷酰胺致血虚小鼠的补血作用及机制[J].中华中医药杂志,2016,31(5):1892-1896.
[11]Xie P,Cui L,Shan Y,et al.Antithrombotic effect and mechanism of radix paeoniae rubra[J].Bio Med Research International,2017,2017:1-9.
[12]李伟,王景霞,葛阳,等.芍药苷对血虚肝郁证模型大鼠海马谷氨酸及其不同类型受体m RNA表达的影响[J].中华中医药杂志,2016,31(4):1241-1244.
[13]王景霞,周恬恬,朱映黎,等.芍药苷对血虚肝郁证大鼠海马CA1区s GCβ1和5种PDE亚型蛋白表达的影响[J].环球中医药,2016,9(7):790-794.
[14]Li X,Shi F,Zhang R,et al.Pharmacokinetics,Safety,and Tolerability of Amygdalin and Paeoniflorin After Single and Multiple Intravenous Infusions of Huoxue-Tongluo Lyophilized Powder for Injection in Healthy Chinese Volunteers[J].Clinical Therapeutics,2016,38(2):327-337.
[15]王成龙,王林元,王景霞,等.芍药内酯苷及芍药苷对慢性束缚应激配合孤养肝郁模型大鼠行为学及下丘脑-垂体-肾上腺轴的影响[J].中华中医药杂志,2017,32(7):3121-3125.
[16]周恬恬,王林元,王景霞,等.芍药苷对血虚肝郁证大鼠海马磷酸二酯酶不同亚型的影响[J].北京中医药大学学报,2016,39(4):288-292.