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目的探讨桂枝汤不同桂芍配伍比例对6-羟基多巴胺(6-hydroxydopamine,6-OHDA)诱导的心脏去交感神经模型大鼠心肌神经递质及其限速酶和神经营养因子的影响。方法将54只雄性Wistar大鼠随机分为6组:空白对照组、模型组、弥可保组、桂枝汤桂芍2∶1组、桂枝汤桂芍1∶2组及桂枝汤桂芍1∶1组,每组9只。连续腹腔注射3日6-OHDA制备心脏去交感神经模型。弥可保组和桂枝汤组于造模前1周开始药物灌胃,弥可保组给予弥可保[0.15 mg/(kg·d)]灌胃,桂枝汤桂芍1∶1组、桂枝汤桂芍1∶2组和桂枝汤桂芍2∶1组分别按4.0、5.5和5.5 g生药/(kg·d)给予桂枝汤水煎剂灌胃。共给药10日。采用ELISA法检测各组大鼠右心房和室间隔去甲肾上腺素(norepinephrine,NE)、酪氨酸羟化酶(tyrosine hydroxylase,TH)、胆碱乙酰氨基转移酶(choline acetyltransferase,ChAT)、神经生长因子(nerve growth factor,NGF)、生长相关蛋白43(growth associated protein 43,GAP-43)及睫状神经营养因子(ciliary neurotrophic factor,CNTF)水平。结果与空白对照组比较,模型组右心房和室间隔NE、TH、TH/ChAT及GAP-43水平降低,NGF含量升高(P<0.01,P<0.05)。与模型组比较,弥可保及桂枝汤各组右心房及室间隔NE、GAP-43水平升高,室间隔NGF水平降低;桂芍2∶1、1∶1组右心房TH、TH/ChAT比例升高,桂芍1∶1组右心房及室间隔NGF含量均降低(P<0.01,P<0.05)。与弥可保组比较,桂芍1∶1组右心房及室间隔NE、TH及GAP-43水平升高,NGF含量降低(P<0.05);桂芍2∶1组室间隔NE及GAP-43含量升高(P<0.05)。结论桂枝汤桂芍2∶1及桂芍1∶1配伍可改善6-OHDA诱导的去交感神经模型大鼠心肌中神经递质及其限速酶和神经营养因子水平,减轻6-OHDA引起的交感神经损伤,维持心脏中交感-迷走神经平衡。
Objective To investigate the effect of different proportion of Guizhi Decoction on the cardiac neurotransmitter and its rate-limiting enzyme and neurotrophic factor in 6-hydroxydopamine (6-OHDA) -induced cardiac denervated rat model. Methods Fifty-four male Wistar rats were randomly divided into 6 groups: control group, model group, Mi Kebao group, Guizhi Decoction 2: 1 group, Guizhi Tang Gu Shao 1: 2 group and Guizhi Tang Gu Shao 1: Each group of 9. Cardiac desytasia models were prepared by continuous intraperitoneal injection of 6-OHDA on day 3. Mi Kebao group and Guizhi decoction group were given gavage one week before model making. Miraculous group was given intragastric gavage [0.15 mg / (kg · d)], Guizhi Decoction group 1: 1, Zhizoupi 1: 2 group and Guizhi soup Guizao 2: 1 group were given 4.0, 5.5 and 5.5 g crude drug / (kg · d) Guizhi decoction given intragastrically. Total administration of 10 days. The right atrium and septal norepinephrine (NE), tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), nerve growth Nerve growth factor (NGF), growth associated protein 43 (GAP-43) and ciliary neurotrophic factor (CNTF). Results Compared with the blank control group, the levels of NE, TH, TH / ChAT and GAP-43 in the right atrium and the septum of the model group decreased and the NGF content increased (P <0.01, P <0.05). Compared with the model group, the levels of NE and GAP-43 in the right atrium and the interventricular septum were increased and the levels of interventricular septum NGF were decreased in the groups of Miqibao and Guizhi decoction; TH, TH / The ratio of ChAT increased, the content of right atrium and interventricular septum NGF in 1: 1 group decreased (P <0.01, P <0.05). Compared with the miconopsis group, the levels of NE, TH and GAP-43 in the right atrium and the interventricular septum of Guizhu 1: 1 group were significantly increased and the contents of NGF were decreased (P <0.05) 43 content increased (P <0.05). Conclusion Guizhi decoction of Guizhao 2: 1 and Guizhi 1: 1 can improve 6-OHDA-induced neurotransmitter and its rate-limiting enzyme and neurotrophic factor in the myocardium and reduce the sympathetic response induced by 6-OHDA Nerve damage, maintaining sympathetic-vagal balance in the heart.