Effect of Guizhitang with Different Proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on Overactive Activation of Cardiac Sympathetic Nervous System in Salt-Sensitive Hypertensive Rats

Xiao-wei HAN; Yong-cheng WANG; Du-fang MA; Yuan LI; Feng DONG; Heng-yi ZHAO; Ping JIANG; Wen-jing CHEN; Ji-ye CHEN; Chen-yu CHI; Xiao LI

doi:10.13422/j.cnki.syfjx.20210140

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Effect of Guizhitang with Different Proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on Overactive Activation of Cardiac Sympathetic Nervous System in Salt-Sensitive Hypertensive Rats

更新时间：2021-12-03

- Effect of Guizhitang with Different Proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on Overactive Activation of Cardiac Sympathetic Nervous System in Salt-Sensitive Hypertensive Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 1, Pages: 81-87(2021)
- 作者机构：
  
  1.山东中医药大学，济南 250014
  2.山东中医药大学附属医院，济南 250014
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20210140
  CLC： R2-0;R289;R285.5;R541.3
- Received：30 June 2020，
  
  Published Online：10 November 2020，
  
  Published：05 January 2021
- 稿件说明：
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韩晓伟,王永成,马度芳等.桂枝汤桂枝-白芍不同比例配伍对盐敏感高血压大鼠心脏交感神经过度激活的影响[J].中国实验方剂学杂志,2021,27(01):81-87.

HAN Xiao-wei,WANG Yong-cheng,MA Du-fang,et al.Effect of Guizhitang with Different Proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on Overactive Activation of Cardiac Sympathetic Nervous System in Salt-Sensitive Hypertensive Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(01):81-87.
韩晓伟,王永成,马度芳等.桂枝汤桂枝-白芍不同比例配伍对盐敏感高血压大鼠心脏交感神经过度激活的影响[J].中国实验方剂学杂志,2021,27(01):81-87. DOI： 10.13422/j.cnki.syfjx.20210140.

HAN Xiao-wei,WANG Yong-cheng,MA Du-fang,et al.Effect of Guizhitang with Different Proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on Overactive Activation of Cardiac Sympathetic Nervous System in Salt-Sensitive Hypertensive Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(01):81-87. DOI： 10.13422/j.cnki.syfjx.20210140.

摘要

目的

探讨桂枝汤桂枝-白芍不同比例配伍对盐敏感高血压大鼠心脏交感神经过度激活的影响及其作用机制。

方法

将40只6周龄雄性盐敏感大鼠随机分为5组，空白组、模型组、桂枝汤组（桂枝-白芍1∶1组、桂枝-白芍1∶2组和桂枝-白芍2∶1组）每组8只，空白组给予低盐饲料饲养，其余4组给予8%高盐饲料饲养，饲养4周后灌胃，空白组、模型组大鼠每天给予2 mL·kg

-1

生理盐水灌胃，桂枝-白芍1∶1组、桂枝-白芍1∶2组和桂枝-白芍2∶1组每天分别按4.0，5.5，5.5 g·kg

-1

给予桂枝汤水煎剂灌胃，连续干预4周。IITC多通道无创血压计检测大鼠治疗前后收缩压变化；超声心动图检测左室前壁舒张末期厚度（LVAWd）和室间隔舒张期厚度（IVSd）以反应心肌肥厚程度；苏木素-伊红（HE）染色和马松（Masson）染色观察大鼠心肌形态学变化；蛋白免疫印迹法（Western blot）检测各组大鼠心肌组织神经生长因子（NGF），生长相关蛋白43（GAP43）和酪氨酸羟化酶（TH）蛋白的表达。

结果

桂枝汤干预4周后，与空白组比较，模型组大鼠血压，LVAWd和IVSd显著升高，NGF，TH和GAP43蛋白表达显著增高（

0.01）；HE和Masson染色结果显示，模型组大鼠心肌细胞水肿，大量炎性细胞浸润，心肌纤维大量增生且排列紊乱，细胞间质可见大量胶原沉积。与模型组比较，桂枝汤各组大鼠收缩压上升缓慢，NGF，TH和GAP43蛋白表达明显降低（

0.05，

0.01），以桂枝-白芍1∶1组效果最佳；超声心动图结果显示，与模型组比较，桂枝-白芍1∶1组可降低LVAWd和IVSd（

0.05，

0.01）；桂枝-白芍1∶2组可明显降低IVSd（

0.05），但LVAWd与模型组比较，差异无统计学意义；桂枝-白芍2∶1组LVAWd和IVSd均无统计学差异；心肌形态学方面，桂枝汤各组较模型组均可减轻细胞水肿和炎性细胞浸润，减少心肌纤维增生和胶原沉积，改善心肌纤维排列紊乱，其中以桂枝汤桂枝-白芍1∶1组效果最佳。

结论

桂枝汤可抑制心脏交感神经系统过度激活，减轻心肌纤维化、炎症浸润和心肌肥厚，对盐敏感高血压大鼠起到保护作用，其机制可能与调节心脏NGF表达有关，其中桂枝汤桂枝-白芍1∶1配伍组在减轻心肌纤维化、炎症浸润和心肌肥厚方面，优于桂枝-白芍1∶2和2∶1组。

Abstract

Objective

To explore the effect and mechanism of Guizhitang with different proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on overactive cardiac sympathetic nerves in salt-sensitive hypertensive rats.

Method

Randomly divide the forty male 6-week-old salt-sensitive hypertensive rats into five groups： the normal control group， the model group， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶2 group，and the Cinnamomi Ramulus and Paeoniae Alba Radix 2∶1 group， each group has 8 animals， the normal control group was fed with low-salt feed， and the remaining four groups were fed with 8% high-salt feed. After 4 weeks of feeding， gastric feeding was started. Give both the normal control group and model group saline and the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group， the 1∶2 group，and the 2∶1 group， were given Guizhitang aqueous solution at 4.0， 5.5 and 5.5 g·kg

-1

， respectively. Continuous gavage intervention was held for 4 weeks. IITC multi-channel non-invasive sphygmomanometer was used to detect changes of systolic blood pressure before and after treatment in rats. Left ventricular anterior wall end-diastolic thickness （LVAWd） and interventricular septal diastolic thickness （IVSd） were detected by echocardiography. Hematoxylin-eosin（HE）staining and Masson staining were used to observe the myocardial morphological changes of rats in each group， Western blot was used to detect the expression of nerve growth factor （NGF）， growth-associated protein 43 （GAP43） and tyrosine hydroxylase （TH） protein.

Result

After 4 weeks of intervention with Guizhitang， compared with the normal control group， the blood pressure， LVAWd and IVSd of the model group were significantly increased， and the expressions of NGF， TH and GAP43 protein were significantly increased （

0.01）. HE and Masson staining results showed that the model group had myocardial cell edema， a large number of inflammatory cell infiltration， myocardial fiber hyperplasia and disordered arrangement， and a large amount of collagen deposition could be seen in the intercellular substance. Compared with model group， the systolic blood pressure of rats in each Guizhitang group increased slowly， and the expression of NGF， TH and GAP43 protein decreased （

0.05，

0.01），the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group has the best effect. The results of echocardiography shows that the 1∶1 Guishao group could reduce LVAWd and IVSd levels （

0.05，

0.01）， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶2 group could reduce IVSd level （

0.05）， there was no statistical difference in LVAWd， there was no statistical difference in LVAWd and IVSd in 2∶1 group. In terms of myocardial morphology， each group of Guizhitang can reduce cell edema and inflammatory cell infiltration， reduce myocardial fiber hyperplasia and collagen deposition， and improve the disorder of myocardial fiber arrangement. Among them， the 1∶1 group has the best effect.

Conclusion

Guizhitang can inhibit the overactive activation of cardiac sympathetic nervous system，reduce the extent of myocardial fibrosis， inflammatory infiltration and myocardial hypertrophy， and protect salt-sensitive hypertension rats， whose mechanism may be related to regulating the expression of heart NGF.Among them， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group is better than the 1∶2 and 2∶1 group in reducing myocardial fibrosis， inflammatory infiltration and myocardial hypertrophy.

关键词

Keywords

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