桂枝汤不同桂芍比例配伍对6-OHDA诱导的心脏去交感神经损伤模型大鼠心肌的保护作用  

Preventive Effect of Different Compatibilities of Ramulus Cinnamomi and Radix Paeomiae alba in Guizhi Decoction on Cardiac Sympathetic Denervation Induced by 6-OHDA

作　　者：姜萍[1] 马度芳 姜月华[2] 杨金龙[2] 徐向东[2] 王雪[1] 林海青[2] 李晓[2] 

机构地区：[1]山东中医药大学第一临床医学院,济南250355 [2]山东中医药大学附属医院心内科,济南250011

出　　处：《中国中西医结合杂志》2016年第5期608-613,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81072962)

摘　　要：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 observe the preventive effect of different compatibilities of Ramulus Cinnamomi（RC） and Radix Paeomiae alba（RPA） in Guizhi Decoction（GZD） on neurotransmitters and their rate-limiting enzymes, and neurotrophic factors of cardiac sympathetic denervation model rats induced by 6-hydroxydopamine（6-OHDA）. Methods Totally 54 male Wistar rats were randomly divided into 6 groups, i.e., the blank control group,the model group, the methycobal group, the 2 ∶ 1（RC/RPA） Guishao group, the 1 ∶ 2 Guishao group, and the 1 ∶ 1Guishao group, 9 in each group. Sympathetic denervation was induced by intraperitoneal injection of 6-OHDA for three successive days. Rats in the methycobal group and GZD groups were administered with corresponding de-coction by gastrogavage 1 week before modeling（methycobal at the daily dose 0. 15 mg/kg;GZD at the dailydose of 4. 0, 5. 5, 5. 5 g crude drugs/kg for GZD 1 ∶ 1, 1∶ 2, and 2∶ 1 groups）. Al medication lasted for 10 successive days. Levels of norepinephrine（NE）, tyrosine hydroxylase（TH）, choline acetyl-transferase（Ch AT）, nerve growth factor（NGF）, growth associated protein43（GAP-43） and ciliary neurotrophic factor（CNTF） in myocardial homogenates of right atrium and ventricular septum were detected by ELISA. Results Compared with the blank control group, levels of NE, TH, TH/Ch AT ratio, and GAP-43 in myocardial homogenates of right atrium and ventricular septum decreased in the model group, and level of NGF increased（P〈0. 01, P〈0. 05）. Compared with the model group, levels of NE and GAP-43 increased in the right atrium and interventricular septum;NGF level of the ventricular septum decreased in the methycobal group and each GZD groups. TH and TH/Ch AT ratio in the right atrium increased in the 2 ∶ 1 Guishao group and the 1 ∶ 2 Guishao group（P〈0. 01, P〈0. 05）;NGF levels in the right atrium and interventricular septum decreased only in the 1 ∶ 1 Guishao group（P〈0. 01, P〈0. 05）. Compared with the met

关 键 词：桂枝汤 化学去交感神经 交感神经失支配 6-羟基多巴胺 心肌保护 

分 类 号：R285.5[医药卫生—中药学]